A Study To Evaluate PF-04449913 With Chemotherapy In Pati... | NCT01546038 | Trialant
NCT01546038
Sponsor
Pfizer
Status
Completed
Last Update Posted
Mar 3, 2020Actual
Enrollment
255Actual
Phase
Phase 2
Conditions
Acute Myeloid Leukemia
Interventions
PF-04449913
Low dose ARA-C (LDAC)
PF-04449913
Decitabine
PF-04449913
Daunorubicin
Cytarabine
PF-04449913
Daunorubicin
Cytarabine
PF-04449913
Low dose ARA-C (LDAC)
Countries
United States
Canada
Germany
Italy
Poland
Spain
Protocol Section
Identification Module
NCT ID
NCT01546038
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
B1371003
Secondary IDs
ID
Type
Description
Link
2012-000684-24
EudraCT Number
Brief Title
A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
Official Title
A PHASE 1B/2 STUDY TO EVALUATE THE SAFETY AND EFFICACY OF PF-04449913, AN ORAL HEDGEHOG INHIBITOR, IN COMBINATION WITH INTENSIVE CHEMOTHERAPY, LOW DOSE ARA-C OR DECITABINE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME
Acronym
Not provided
Organization
PfizerINDUSTRY
Status Module
Record Verification Date
Feb 2020
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Jun 27, 2012Actual
Primary Completion Date
Jan 3, 2017Actual
Completion Date
Mar 4, 2019Actual
First Submitted Date
Mar 1, 2012
First Submission Date that Met QC Criteria
Mar 1, 2012
First Posted Date
Mar 7, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Dec 11, 2017
Results First Submitted that Met QC Criteria
May 16, 2018
Results First Posted Date
May 23, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 19, 2020
Last Update Posted Date
Mar 3, 2020Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
PfizerINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.
Detailed Description
Not provided
Conditions Module
Conditions
Acute Myeloid Leukemia
Keywords
Hedgehog Inhibitor
Acute Myeloid Leukemia
Myelodysplastic syndrome
Intensive chemotherapy
LDAC
glasdegib
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
255Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Arm A (Phase 1B)
Experimental
PF-04449913 in combination with low dose ARA-C (LDAC)
Drug: PF-04449913
Drug: Low dose ARA-C (LDAC)
Arm B (Phase 1B)
Experimental
PF-04449913 in combination with Decitabine
Drug: PF-04449913
Drug: Decitabine
Arm C (Phase 1B)
Experimental
PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
Drug: PF-04449913
Drug: Daunorubicin
Drug: Cytarabine
P2 Fit (Phase 2 Single Arm)
Experimental
PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
Drug: PF-04449913
Drug: Daunorubicin
Drug: Cytarabine
P2 Unfit (Phase 2 Randomized)
Other
Interventions
Name
Type
Description
Arm Group Labels
Other Names
PF-04449913
Drug
PF-04449913 administered orally and continuously for 28-days.
Arm A (Phase 1B)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.
Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started
Percentage of Participants With Complete Response (CR) at Phase 2 Fit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
4 years
Overall Survival (OS) at Phase 2 Unfit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.
Secondary Outcomes
Measure
Description
Time Frame
Overall Survival (OS) at Phase 1B
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
For a diagnosis of AML, a bone marrow blast count of 20% or more is required.
For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts
Adequate Organ Function
ECOG Performance Status 0, 1, or 2
Exclusion Criteria:
AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation.
Patients with known active uncontrolled central nervous system (CNS) leukemia.
Heuser M, Smith BD, Fiedler W, Sekeres MA, Montesinos P, Leber B, Merchant A, Papayannidis C, Perez-Simon JA, Hoang CJ, O'Brien T, Ma WW, Zeremski M, O'Connell A, Chan G, Cortes JE. Clinical benefit of glasdegib plus low-dose cytarabine in patients with de novo and secondary acute myeloid leukemia: long-term analysis of a phase II randomized trial. Ann Hematol. 2021 May;100(5):1181-1194. doi: 10.1007/s00277-021-04465-4. Epub 2021 Mar 19.
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Phase 1B:Unfit(unfit for intensive chemotherapy)participants with prior decitabine or azacitidine for high risk MDS or AHD(antecedent hematologic disease)were eligible for the LDAC arm only;with prior cytarabine were eligible for decitabine arm only.Phase 2:Participant's treatment arm assignment was based on the fit or unfit status at screening.
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Not provided
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).
Drug: PF-04449913
Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC)
Drug
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
Arm A (Phase 1B)
PF-04449913
Drug
PF-04449913 administered orally and continuously for 28 days.
Arm B (Phase 1B)
Decitabine
Drug
Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days
Arm B (Phase 1B)
PF-04449913
Drug
PF-04449913 administered orally and continuously for 28 days
Arm C (Phase 1B)
Daunorubicin
Drug
Daunorubicin given using 60 mg/m2 for 3-days
Arm C (Phase 1B)
Cytarabine
Drug
Cytarabine 100 mg/m2 on days 1 through 7
Arm C (Phase 1B)
PF-04449913
Drug
PF-04449913 administered orally and continuously for 28 days
P2 Fit (Phase 2 Single Arm)
Daunorubicin
Drug
Daunorubicin given using 60 mg/m2 for 3-days
P2 Fit (Phase 2 Single Arm)
Cytarabine
Drug
Cytarabine 100 mg/m2 on days 1 through 7
P2 Fit (Phase 2 Single Arm)
PF-04449913
Drug
PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
P2 Unfit (Phase 2 Randomized)
Low dose ARA-C (LDAC)
Drug
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
P2 Unfit (Phase 2 Randomized)
Randomization to Follow-up (4 years)
First dose to Follow-up (4 years)
Overall Survival (OS) at Phase 2 Fit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
First dose to Follow-up (4 years)
Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL).
4 years
Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
4 years
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative).
4 years
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).
4 years
Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Pre-dose Plasma Concentration (Ctrough) of Glasdegib in Phase 2 Fit on Induction Cycle 1/Day 10
Pre-dose, 1 and 4 hours post-dose on Induction Cycle 1/Day 10
Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
Number of Participants With Disease-related Gene Mutations at Phase 1B
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Baseline (Induction Cycle 1/Day -3 pre-dose)
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.
Induction Cycle 1/Day 3, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Induction Cycle 1/Day 10, 1 Hour Post dose
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.
Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.
Induction Cycle 1/Lead-in, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.
Induction Cycle 1/Day 3, 1 Hour Post dose
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Induction Cycle 1/Day 3, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Induction Cycle 1/Day 10, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Consolidation Cycle 1/Day 1, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
Consolidation Cycle 1/Day 10, Pre-dose
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Baseline (Induction Cycle 1/Day -3 pre-dose)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Induction Cycle 1/Day 3, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
Induction Cycle 1/Day 10, 1 Hour Post dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.
Cycle 1/Day 1, 1 Hour Post dose
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.
Cycle 1/Day 10, Pre-dose
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Baseline (Cycle 1/Day 1 pre-dose)
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
Cycle 1/Day 1, 1 Hour Post-dose
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.
Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.
Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).
Baseline (Induction Cycle 1/Day -3 pre-dose)
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.
Baseline (Cycle 1/Day 1 pre-dose)
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.
Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
1 year
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
1 year
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
4 years
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
4 years
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
4 years
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
4 years
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
4 years
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
4 years
Birmingham
Alabama
35249-6909
United States
University of Alabama at Birmingham
Birmingham
Alabama
35249
United States
UC San Diego Moores Cancer Center - Investigational Drug Services
La Jolla
California
92037-0845
United States
UC San Diego Medical Center - La Jolla
La Jolla
California
92037
United States
UC San Diego Moores Cancer Center
La Jolla
California
92093-0698
United States
Keck Hospital of USC
Los Angeles
California
90033
United States
LAC & USC Medical Center
Los Angeles
California
90033
United States
USC/Norris Comprehensive Cancer Center / Investigational Drug Services
Los Angeles
California
90033
United States
USC/Norris Comprehensive Cancer Center
Los Angeles
California
90033
United States
Ronald Reagan UCLA Medical Center Drug Information Center
Los Angeles
California
90095
United States
Ronald Reagan UCLA Medical Center
Los Angeles
California
90095
United States
UCLA Drug lnformation/lnvestigational Drugs
Los Angeles
California
90095
United States
UCLA Hematology/Oncology Clinic
Los Angeles
California
90095
United States
UC San Diego Medical Center - Hillcrest
San Diego
California
92103
United States
University of Colorado Denver
Aurora
Colorado
80045
United States
University of Colorado Hospital
Aurora
Colorado
80045
United States
H.Lee Moffitt Cancer Center and Research Institute
Tampa
Florida
33612
United States
Emory University Hospital
Atlanta
Georgia
30322
United States
Investigational Drug Service, Emory University Clinic
Atlanta
Georgia
30322
United States
The Emory Clinic
Atlanta
Georgia
30322
United States
Winship Cancer Institute, Emory University
Atlanta
Georgia
30322
United States
Northwestern Medical Faculty Foundation
Chicago
Illinois
60611
United States
Northwestern Medicine Developmental Therapeutics Institute
Chicago
Illinois
60611
United States
Northwestern Memorial Hospital
Chicago
Illinois
60611
United States
The University of Chicago Medical Center
Chicago
Illinois
60637
United States
The University of Chicago's Medical Center
Chicago
Illinois
60637
United States
University of Kansas Clinical Research Center
Fairway
Kansas
66205
United States
University of Kansas Hospital
Kansas City
Kansas
66160
United States
University of Kansas Cancer Center and Medical Pavilion
Westwood
Kansas
66205
United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Baltimore
Maryland
21287
United States
Tufts Medical Center
Boston
Massachusetts
02111
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Brigham and Women's Hospital
Boston
Massachusetts
02115
United States
Dana Farber Cancer Institute (DFCI)
Boston
Massachusetts
02215
United States
University of Michigan Comprehensive Cancer Center Clinical Trials Office
Ann Arbor
Michigan
48109-2800
United States
University of Michigan Health System
Ann Arbor
Michigan
48109
United States
Siteman Cancer Center - West County
Creve Coeur
Missouri
63141
United States
Barnes Jewish Hospital North Campus
St Louis
Missouri
63110
United States
Barnes-Jewish Hospital
St Louis
Missouri
63110
United States
Washington University School of Medicine - Division of Bone Marrow Transplant & Leukemia
St Louis
Missouri
63110
United States
Washington University School of Medicine, Siteman Cancer Center
St Louis
Missouri
63110
United States
Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
John Theurer Cancer Center at Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
Cleveland Clinic Cancer Institute
Cleveland
Ohio
44195
United States
Centennial Medical Center
Nashville
Tennessee
37203
United States
Sarah Cannon Research Institute
Nashville
Tennessee
37203
United States
Tennessee Oncology, PLLC
Nashville
Tennessee
37203
United States
The University of Texas, MD Anderson Cancer Center
Houston
Texas
77030
United States
University of Washington-Seattle Cancer Care Alliance
Seattle
Washington
98109
United States
University of Washington Medical Center
Seattle
Washington
98195
United States
Juravinski Cancer Centre @ Hamilton Health Sciences
Hamilton
Ontario
L8V 5C2
Canada
Centre de Sante et de Services Sociaux (CSSS) Champlain - Charles-Le Moyne
Greenfield Park
Quebec
J4V 2H1
Canada
Universitaetsklinikum Ulm
Ulm
Baden-Wurttemberg
89081
Germany
Johann Wolfgang Goethe University
Frankfurt am Main
Hesse
60590
Germany
Medizinische Hochschule Hannover
Hanover
Lower Saxony
30625
Germany
Charite -Universitatsmedizin Berlin - Campus Benjamin Franklin
Berlin
12203
Germany
Charite - Universitatsmedizin Berlin
Berlin
13353
Germany
Universitaetsklinikum Hamburg-Eppendorf
Hamburg
20246
Germany
Universitaetsklinikum Schleswig-Holstein
Kiel
24105
Germany
Universitaetsklinikum Magdeburg A.oe.R.
Magdeburg
39120
Germany
Johannes Gutenberg-Universitaet Mainz
Mainz
55131
Germany
Universitaetsklinikum Muenster
Münster
48149
Germany
Universitaetsklinikum Ulm
Ulm
89081
Germany
Policlinico S. Orsola-Malpighi
Bologna
Province OF Bologna
40138
Italy
ASST Grande Ospedale Metropolitano Niguarda
Milan
20162
Italy
Policlinico Universitario "Umberto I" Universita degli Studi "La Sapienza" Sezione di Ematologia
Rome
00161
Italy
A.O. Citta della Salute e della Scienza di Torino - S.C. Ematologia
Torino
10126
Italy
Azienda Sanitaria Universitaria Integrata di Udine
Udine
33100
Italy
Uniwersyteckie Centrum Kliniczne Gdanskiego Uniwersytetu Medycznego
Gdansk
Pomeranian Voivodeship
80-952
Poland
Oddzial Hematologii Z pododzialem chemioterapii-Klinika Hematologii Wojewodzkie Wielospecjalistyczne
Lodz
93-513
Poland
Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku
Wroclaw
53-439
Poland
Hospital Universitario Virgen del Rocio
Seville
Andalusia
41013
Spain
Hospital Universitario Germans Trias i Pujol
Badalona
Barcelona
08916
Spain
Hospital del Mar
Barcelona
08003
Spain
Hospital de la Santa Creu i Sant Pau
Barcelona
08025
Spain
Hospital Universitari Vall d'Hebron
Barcelona
08035
Spain
Hospital Clinic de Barcelona
Barcelona
08036
Spain
Hospital Ramon y Cajal
Madrid
28034
Spain
Hospital Universitario y Politecnico La Fe
Valencia
46026
Spain
Derived
Lin S, Shaik N, Chan G, Cortes JE, Ruiz-Garcia A. An evaluation of overall survival in patients with newly diagnosed acute myeloid leukemia and the relationship with glasdegib treatment and exposure. Cancer Chemother Pharmacol. 2020 Oct;86(4):451-459. doi: 10.1007/s00280-020-04132-x. Epub 2020 Sep 3.
Cortes JE, Heidel FH, Fiedler W, Smith BD, Robak T, Montesinos P, Candoni A, Leber B, Sekeres MA, Pollyea DA, Ferdinand R, Ma WW, O'Brien T, O'Connell A, Chan G, Heuser M. Survival outcomes and clinical benefit in patients with acute myeloid leukemia treated with glasdegib and low-dose cytarabine according to response to therapy. J Hematol Oncol. 2020 Jul 14;13(1):92. doi: 10.1186/s13045-020-00929-8.
Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, Montesinos P, Pollyea DA, DesJardins P, Ottmann O, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Heuser M. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia. 2019 Feb;33(2):379-389. doi: 10.1038/s41375-018-0312-9. Epub 2018 Dec 16.
Cortes JE, Douglas Smith B, Wang ES, Merchant A, Oehler VG, Arellano M, DeAngelo DJ, Pollyea DA, Sekeres MA, Robak T, Ma WW, Zeremski M, Naveed Shaik M, Douglas Laird A, O'Connell A, Chan G, Schroeder MA. Glasdegib in combination with cytarabine and daunorubicin in patients with AML or high-risk MDS: Phase 2 study results. Am J Hematol. 2018 Nov;93(11):1301-1310. doi: 10.1002/ajh.25238. Epub 2018 Sep 9.
Savona MR, Pollyea DA, Stock W, Oehler VG, Schroeder MA, Lancet J, McCloskey J, Kantarjian HM, Ma WW, Shaik MN, Laird AD, Zeremski M, O'Connell A, Chan G, Cortes JE. Phase Ib Study of Glasdegib, a Hedgehog Pathway Inhibitor, in Combination with Standard Chemotherapy in Patients with AML or High-Risk MDS. Clin Cancer Res. 2018 May 15;24(10):2294-2303. doi: 10.1158/1078-0432.CCR-17-2824. Epub 2018 Feb 20.
FG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
FG002
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
FG003
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
FG007
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.
FG008
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
FG00017 subjects
FG0016 subjects
FG0024 subjects
FG0033 subjects
FG00416 subjects
FG0056 subjects
FG00671 subjects
FG00788 subjects
FG00844 subjects
Received Treatment
FG00017 subjects
FG0016 subjects
FG0024 subjects
FG0033 subjects
FG00416 subjects
FG0056 subjects
FG00669 subjects
FG00784 subjects
FG00841 subjects
COMPLETED
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0046 subjects
FG0052 subjects
FG00618 subjects
FG0074 subjects
FG0081 subjects
NOT COMPLETED
FG00016 subjects
FG0016 subjects
FG0024 subjects
FG0033 subjects
FG00410 subjects
FG0054 subjects
FG00653 subjects
FG00784 subjects
FG00843 subjects
Type
Comment
Reasons
Death
FG00015 subjects
FG0016 subjects
FG0024 subjects
FG0032 subjects
FG0049 subjects
FG0053 subjects
FG00646 subjects
FG00776 subjects
FG00839 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
: Randomized, not treated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
BG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
BG002
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
BG004
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.
BG005
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
BG006
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00023
BG0017
BG00222
BG00371
BG00488
BG00544
BG006255
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
Years
Title
Denominators
Categories
Title
Measurements
BG00075.8± 6.5
BG00175.0± 4.4
BG00254.9± 12.7
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0008
BG0012
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Dose-limiting Toxicities (DLTs) at Phase 1B
A DLT was any of the following adverse events (AEs) in Cycle 1 and considered by the investigator possibly related to glasdegib in combination with chemotherapy: (1) Grade >= 3 non-hematologic toxicity, excluding Grade >= 3 infection, fever (including febrile neutropenia), infusion related AEs, electrolyte abnormalities and ALT/AST elevation that returned to Grade <= 1 or baseline within 7 days; (2) prolonged myelosuppression that lasted longer than 42 days from the point of detection, defined as absolute neutrophil count (ANC) < 500/microliter(mcL) or platelet count < 10 *10^9/L with a normal bone marrow (<5% blasts and no evidence of disease or dysplasia); (3) inability to deliver at least 80% of the planned study doses for all agents in a combination due to non-hematologic toxicities; (4) Delay of >28 days in receiving the next scheduled cycle due to persisting non-hematologic toxicities. Arm A: Glasdegib+LDAC; Arm B: Glasdegib+Decitabine; Arm C: Glasdegib+Cytarabine/Daunorubicin.
Per protocol analysis set: all enrolled participants in the dose escalation component who received at least 1 dose of glasdegib and of the co-administered chemotherapeutics and who did not have major treatment deviations during the DLT monitoring period.
Posted
Number
Participants
Arms A and B: Cycle 1, Day 1 to Day 28; Arm C: Cycle 1, Day -3 to Day 21 or to Day 28 depending on when the next chemotherapy cycle was started
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
OG002
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG003
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Units
Counts
Participants
OG0003
OG0015
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
Percentage of Participants With Complete Response (CR) at Phase 2 Fit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Primary
Overall Survival (OS) at Phase 2 Unfit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from time of randomization for each participant.
Full analysis set: all randomized participants of Phase 2 Unfit arm.
Posted
Median
80% Confidence Interval
Months
Randomization to Follow-up (4 years)
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG001
Phase 2 Unfit: LDAC Alone
Secondary
Overall Survival (OS) at Phase 1B
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.
Posted
Median
80% Confidence Interval
Months
First dose to Follow-up (4 years)
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
OG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Secondary
Overall Survival (OS) at Phase 2 Fit
OS was defined as duration from the date of randomization to the date of death from any cause. Kaplan-Meier (KM) method was used to estimate median OS. In this method, every participant had a follow-up time which was associated with an indicator, 1=event (death in our case), and 0 =censored. If the participants were not known to have died, time to date of last known to be alive was used as to calculate the follow-up time and indicator was 0 for these participants. KM method estimates the median OS based on the K-M curve. The K-M curve only drops when we had an event and censor data are the ticks in the graph. To estimate median OS, the K-M curve usually will be smoothed first and a line will be drawn at 50%. The median OS is the point when K-M curve and the horizontal hit. Survival status was collected every month for the first 2 months after discontinuation of study treatment and thereafter every 2 months until death or 4 years from each participant's first dose.
Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication. Number of participants analyzed signifies number of participants who were evaluable for this outcome measure. Number analyzed refers to number of participants evaluable for specified rows of categories.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Percentage of Participants With CR / Complete Response With Incomplete Blood Count Recovery (CRi) at Phase 1B
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.For AML and MDS participants, complete response with incomplete blood count recovery(CRi)were those with repeat bone marrow showing <5% myeloblasts with either platelets or neutrophils not recovered (platelets <100,000/mcL or neutrophils <1000/mcL).
Full analysis set: all enrolled participants of Phase 1B portion who received at least 1 dose of study medication.
Posted
Number
80% Confidence Interval
Percentage of participants
4 years
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
OG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
OG002
Secondary
Percentage of Participants With Complete Response (CR) at Phase 2 Unfit
For AML participants:CR were those with repeat bone marrow showing <5% myeloblasts,spicules present and no Auer rods, peripheral blood showing neutrophils>=1000/mcL and platelets>=100,000/mcL, transfusion independent and no extramedullary disease. For MDS participants:CR were those with repeat bone marrow showing <=5% myeloblasts, peripheral blood showing neutrophils>=1000/mcL, platelets>=100,000/mcL, 0% blast and hemoglobin (Hgb)>= 11 g/dL, normal maturation of all cell lines.
Full analysis set: all randomized participants of Phase 2 Unfit arm.
Posted
Number
80% Confidence Interval
Percentage of participants
4 years
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG001
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Secondary
Percentage of Participants With Disease-specific Efficacy for Acute Myeloid Leukemia (AML) at Phase 2 Fit and Unfit
AML participants,disease specific efficacy measures included:CRi;Morphologic Leukemia Free State(MLFS)(bone marrow<5%myeloblasts with spicules and no blasts with auer rods,neutrophils<1000/mcL and platelets<100,000/mcL);partial remission(PR)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start, neutrophils>=1000/mcL, platelets>=100,000/mcL);PR with incomplete blood count recovery(PRi)(bone marrow myeloblasts decrease to 5-25&>=50%decrease from start,neutrophils<1000/mcL or platelets<100,000/mcL);minor response(MR)(bone marrow myeloblasts decrease to>=25% from start);stable disease(SD)(bone marrow myeloblasts stable+/-25% from screening value);cytogenetic complete response(CRc)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and normal cytogenetics),molecular complete response(CRm)(bone marrow<5%myeloblasts, neutrophils>1000/mcL, platelets>100,000/mcL and molecular-negative).
AML participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Percentage of Participants With Disease-specific Efficacy for Myelodysplastic Syndrome (MDS) at Phase 2 Fit and Unfit
For all MDS participants, disease specific efficacy measures included: CRi (bone marrow showing <5% myeloblasts with platelets <100,000/mcL or neutrophils <1000/mcL, including confirmed and unconfirmed responses); PR (repeat bone marrow myeloblasts showing decreased by >= 50% decrease but still >5%, peripheral blood showing neutrophils >= 1,000/mcL, platelets >= 100,000/mcL and Hgb>=11g/dL; including confirmed and unconfirmed responses); SD (including confirmed and unconfirmed responses, failure to achieve PR and no evidence of progression for >8 weeks); marrow complete response (mCR) (bone marrow showing <=5% myeloblasts and decreased by >= 50%), partial cytogenetic response (>=50% reduction of chromosomal abnormality) and complete cytogenetic response (CRc) (disappearance of chromosomal abnormality with no appearance of now ones).
MDS participants in the Full analysis set: all enrolled participants of Phase 2 Fit arm who received at least 1 dose of study medication, and all randomized participants of Phase 2 Unfit arm.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Time to Cmax (Tmax) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Median
Full Range
Hours
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to Dosing Interval (AUCtau) of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 10 and Cycle 1/Day 21
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10 and Cycle 1/Day 21
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Cmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Secondary
Tmax of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Median
Full Range
Hours
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Secondary
AUCtau of Glasdegib in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 10 and Cycle 2/Day 1
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.5, 1, 2, 4, 6 and 24 hours post-dose on Cycle 1/Day 10; pre-dose, 0.5, 1, 2, 6 and 24 hours post-dose on Cycle 2/Day 1
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Secondary
Cmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Secondary
Tmax of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Median
Full Range
Hours
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Secondary
AUCtau of Glasdegib in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3 and Day 10
Dose compliant group:Participants who had at least 4 days of uninterrupted dosing for a multiple dose PK assessment were considered to be at steady state,part of the "dose compliant" group.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.5, 1, 6 and 24 hours post-dose on Induction Cycle 1/Day 3; pre-dose, 0.5, 1, 4, 6 and 24 hours post-dose on Induction Cycle 1/Day 10
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Secondary
Cmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Cmax levels of both LDAC and Ara-U were reported.
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Tmax of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, Tmax levels of both LDAC and Ara-U were reported.
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Median
Full Range
Hours
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to Infinity (AUCinf) of LDAC in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Area Under the Plasma Concentration-time Profile From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of LDAC and Ara-U in Participants Receiving Glasdegib and LDAC at Phase 1B on Cycle 1/Day 2 and Cycle 1/Day 10
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U. Area under the plasma concentration-time profile from time 0 to the time of the last quantifiable concentration (AUClast) levels of both LDAC and Ara-U were reported.
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.25, 0.5, 1, 2, 4 and 6 hours post-dose on Cycle 1/Day 2 and Cycle 1/Day 10
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Cmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
Tmax of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Median
Full Range
Hours
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
AUCinf of Decitabine in Participants Receiving Glasdegib and Decitabine at Phase 1B on Cycle 1/Day 1 and Cycle 1/Day 2
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.5 hour from start of infusion, 1 hour (at end of infusion) and 2, 3 and 4 hours from start of infusion on Cycle 1/Day 1 and Cycle 1/Day 2
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
Secondary
AUCtau of Cytarabine and Ara-U in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Ara-U is the major metabolite of cytarabine. LDAC (low dose cytarabine) is rapidly degraded to the stable metabolite Ara-U, levels of both cytarabine and Ara-U were reported.
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 6 and 24 hours post start of cytarabine infusion on Induction Cycle 1/Day 3
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Cmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Cmax values of daunorubicin and daunorubicinol are reported.
PK concentration population: all treated participants who had at least 1 concentration of any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Tmax of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. Tmax values of daunorubicin and daunorubicinol are reported.
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Median
Full Range
Hours
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
AUCtau of Daunorubicin and Daunorubicinol in Participants Receiving Glasdegib and Cytarabine/Daunorubicin at Phase 1B on Induction Cycle 1/Day 3
Daunorubicinol is the major metabolite of daunorubicin, which has anti-neoplastic activity. AUCtau values of daunorubicin and daunorubicinol are reported.
PK parameter analysis set: all treated participants who had at least 1 of the PK parameters of interest for any of the study drugs.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 0.25, 0.5, 1, 4, 6, 24 hours post administration of daunorubicin on Induction Cycle 1/Day 3
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Units
Counts
Participants
OG000
Secondary
Cmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG000
Secondary
Tmax of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Posted
Median
Full Range
Hours
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG000
Secondary
AUCtau of Glasdegib in Participants Receiving Glasdegib and LDAC at Phase 2 Unfit on Cycle 1/Day 10
Dose compliant, non CYP3A4 group: dose compliant group participants who did not have administration of any strong or moderate CYP3A4 inhibitors.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*hr/mL
Pre-dose, 1, 2, 4, and 6 hour post-dose on Cycle 1/Day 10
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG000
Secondary
Number of Participants With Disease-related Gene Mutations at Phase 1B
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Number
Participants
Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC (Biomarker, Responder)
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Serum Levels of Circulating Protein Analytes at Phase 1B - Baseline
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Baseline (Induction Cycle 1/Day -3 pre-dose)
ID
Title
Description
OG000
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG000
Secondary
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here. Statistically significant, >=2-fold baseline difference was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Day 3.
Pharmacodynamic (PD) analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Induction Cycle 1/Day 3, 1 Hour Post dose
ID
Title
Description
OG000
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG000
Secondary
Serum Levels of Circulating Protein Analytes at Phase 1B - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Values showing statistically significant, ≥2-fold difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Induction Cycle 1/Day 10, 1 Hour Post dose
ID
Title
Description
OG000
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG000
Secondary
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response in Arm C are reported. Baseline levels statistically associated with best overall response was only seen in SDF-1 (stromal cell-derived factor 1) in glasdegib+cytarabine/daunorubicin arm.
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Baseline (Cycle 1/Day 1 pre-dose for Glasdegib + LDAC and Glasdegib + Decitabine Arms; Induction Cycle 1/Day -3 pre-dose for Glasdegib +Cytarabine/Daunorubicin Arm)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Lead-In
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for MMP-3 (Matrix metalloproteinase-3) at Induction Cycle 1/Lead-in.
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 1B - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported. Post-baseline levels statistically significant associated with best overall response was only seen for SDF-1 (Stromal cell-derived factor 1) at Induction Cycle 1/Day 3.
PD analysis set: all enrolled participants in the Phase 1B portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Secondary
Number of Participants With Disease-related Gene Mutations at Phase 2 Fit and Unfit
Peripheral blood and bone marrow aspirate were collected for baseline mutational analyses. Genetic abnormalities frequently associated with AML were analyzed. These genetic abnormalities included known mutations in the genes NPM1, CEBPA, FLT3, RUNX1, IDH1, IDH2, KIT, K Ras, N Ras and WT1. Additional genes with mutations known to be associated with AML and MDS such as TET2 and DNMT3A were also evaluated.
PD analysis set: all enrolled participants in the Phase 2 Fit and Unfit portion who received at least 1 dose of glasdegib; responders and non-responders in each arm with at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Number
Participants
Baseline (Induction Cycle 1/Day -3 pre-dose for Phase 2 Fit; Cycle 1/Day 1 pre-dose for Phase 2 Unfit)
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker,Non-Responder)
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 3
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Units
Counts
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Induction Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Units
Counts
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Units
Counts
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - Consolidation Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Units
Counts
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Fit - End of Treatment
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant difference compared with baseline are reported here.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Baseline (Induction Cycle 1/Day -3 pre-dose)
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 3
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Mean
Full Range
pg/mL
Induction Cycle 1/Day 3, 1 Hour Post dose
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - Induction Cycle 1/Day 10
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Mean
Full Range
pg/mL
Induction Cycle 1/Day 10, 1 Hour Post dose
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Fit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 1
Serum levels were determined for 38 circulating proteins. Selected value showing statistically significant difference compared with baseline is reported here.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Cycle 1/Day 1, 1 Hour Post dose
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG000
Secondary
Serum Levels of Circulating Protein Analytes at Phase 2 Unfit - Cycle 1/Day 10
Serum levels were determined for 38 circulating proteins. Selected values showing statistically significant differences compared with baseline are reported here. ITAC (Interferon-inducible T-cell α chemoattractant) level in LDAC alone arm at Cycle 1/Day 10 exhibited non-significant change from baseline but similar trends as in Glasdegib 100 mg+LDAC arm.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
Cycle 1/Day 10, Pre-dose
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG001
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Secondary
Baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. The data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - Cycle 1/Day 1
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analytes for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Post-baseline Levels of Serum Circulating Protein Analytes Associated With Best Overall Response at Phase 2 Unfit - End of Treatment
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. A total of 38 proteins were analyzed. Selected data of analyte for which the serum level showed statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
pg/mL
End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Ratios of mRNA Levels to Baseline at Phase 2 Fit - Induction Cycle 1/Day 3
Whole blood mRNA analyses were performed on 21 mRNA candidates. Values showing statistically significant, ≥2-fold differences compared with baseline are reported here. CDKN1A: cyclin-dependent kinase inhibitor 1A; SMO: mRNA encoding the glasdegib target Smoothened; PTCH2: Patched 2; MYCN: Neuroblastoma Myc oncogene.
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Ratios of mRNA Levels to Baseline at Phase 2 Fit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Selected values showing statistically significant differences compared with baseline are reported here. CCND2:G1/S-Specific Cyclin D2; MSI2: Musashi RNA Binding Protein 2; PTCH2: Patched 2.
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
ratio
Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Ratios of mRNA Levels to Baseline at Phase 2 Unfit - End of Treatment
Whole blood mRNA analyses were performed on 21 mRNA candidates. Only the analytes showing statistically significant change from baseline are reported here.
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
ratio
Baseline (Cycle 1/Day 1 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
ID
Title
Description
OG000
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG000
Secondary
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. Baseline mRNA levels statistically significant associated with best overall response was only seen for CCND2 (G1/S-Specific Cyclin D2).
PD analysis set: all enrolled participants in the Phase 2 Fit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
Normalized expression units
Baseline (Induction Cycle 1/Day -3 pre-dose)
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Baseline mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Baseline mRNA level showing statistically significant correlation with clinical response are reported. FOXM1: Forkhead box M1; PTCH1: Patched 1.
PD analysis set:all enrolled participants in Phase 2 Unfit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Ratios of mRNA Levels to Baseline Associated With Best Overall Response at Phase 2 Fit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported.
PD analysis set: all enrolled participants in Phase 2 Fit who received at least 1 dose of glasdegib, had at least 1 PD parameter with a baseline and an adequate post treatment assessment.
Posted
Median
Full Range
ratio
Baseline (Induction Cycle 1/Day -3 pre-dose); End of Treatment (maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first, an average of 1 year)
ID
Title
Description
OG000
Phase 2 Fit (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
OG001
Phase 2 Fit (Biomarker, Non-Responder)
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Ratios of mRNA Levels Associated With Best Overall Response at Phase 2 Unfit
Responders were AML participants who achieved CR, CRi, MLFS, PR or PRi based on investigator-reported best overall response and MDS participants who achieved CR, mCR, PR or SD based on investigator-reported best overall response. Whole blood mRNA analyses were performed on 21 mRNA candidates. Ratios of mRNA level to baseline showing statistically significant correlation with clinical response are reported. Ratios of mRNA levels to baseline statistically significant associated with best overall response was only seen for MYCN (Neuroblastoma Myc oncogene) at Cycle 1/Day 1.
PD analysis set: all enrolled participants in the Phase 2 Unfit portion who received at least 1 dose of glasdegib, and had at least 1 PD parameter from the corresponding assay sample with a baseline and an adequate post treatment assessment.
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Secondary
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 1B
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented: QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. Arms in the time frame description are defined as: Arm A, Glasdegib +LDAC; Arm B, Glasdegib + Decitabine; Arm C, Glasdegib + Cytarabine/Daunorubicin. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.
Posted
Number
Participants
1 year
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
OG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
Secondary
Number of Participants With Corrected QT Interval Using Fridericia's Formula (QTcF) Values Meeting Predefined Criteria at Phase 2 Fit and Unfit
Maximum absolute values and increases from baseline were summarized for QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole corrected for heart rate using Fridericia's formula). Number of participants with QTcF meeting the following criteria is presented:QTcF interval:<450 msec; QTcF interval: 450 to <480 msec; QTcF interval: 480 to <500 msec; QTcF interval >=500 msec; QTcF interval increase from baseline: <30 msec; QTcF interval increase from baseline: 30 to <60 msec; QTcF interval increase from baseline >=60 msec. End of treatment in the time frame were defined as: maximum of 12 cycles from start of therapy or until disease progression or relapse, participant refusal or unacceptable toxicity occurred, whichever came first.
QTc analysis set: all participants enrolled in the study having at least 1 ECG assessment after receiving at least 1 dose of glasdegib.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Number of Participants With Treatment-emergent Adverse Events (AEs) at Phase 1B (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Posted
Number
Participants
4 years
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
OG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
OG002
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Secondary
Number of Participants With Treatment-emergent AEs at Phase 1B (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Posted
Number
Participants
4 years
ID
Title
Description
OG000
Phase 1B: Glasdegib + LDAC
Included all participants who received oral glasdegib in combination with LDAC in phase 1B portion.
OG001
Phase 1B: Glasdegib + Decitabine
Included all participants who received oral glasdegib in combination with decitabine in phase 1B portion.
OG002
Secondary
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 1B
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Posted
Number
Participants
4 years
ID
Title
Description
OG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
OG001
Phase 1B: Glasdegib 200 mg + LDAC
Secondary
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (All Causality)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Number of Participants With Treatment-emergent AEs at Phase 2 Fit and Unfit (Treatment-related)
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. Treatment-related AEs were AEs related to glasdegib and/or backbone chemotherapy. AEs were graded by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 : Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated; Grade 5: death related to AE.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Secondary
Number of Participants With Treatment-emergent AEs Categorized by Seriousness at Phase 2 Fit and Unfit
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event did not necessarily had a causal relationship with the treatment or usage. Treatment Emergent AEs were those with initial onset or increasing in severity after the first dose of study medication and occurred within 28 days post last dose. An serious adverse event (SAE) was any untoward medical occurrence at any dose that: resulted in death; was life threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect.
Safety analysis set: all enrolled participants who received at least 1 dose of any of the study medications for each drug combination.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Time Frame
4 years
Description
The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. All-cause mortality reflects the number of deaths from start of treatment to and including 28 days after last dose. Safety analysis set was evaluated.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Phase 1B: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib (PF-04449913) tablets 100 milligram (mg) starting on Day 3 of Cycle 1 for pharmacokinetic (PK) assessment purposes and thereafter once daily (QD) and continuously for 28-day cycles (starting on Day 1 for all other cycles). Low dose Ara-C (LDAC) was given at a dose of 20 mg subcutaneously twice daily (BID) on Days 1-10 of the 28-day cycles.
6
17
13
17
16
17
EG001
Phase 1B: Glasdegib 200 mg + LDAC
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
1
6
5
6
6
6
EG002
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
1
4
4
4
4
4
EG003
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
5
69
35
69
69
69
EG007
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles.
26
84
68
84
82
84
EG008
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28-day cycles.
17
41
32
41
39
41
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0013 affected6 at risk
EG0020 affected4 at risk
EG0031 affected3 at risk
EG004
Acute myocardial infarction
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cardiac failure congestive
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Impaired gastric emptying
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Neutropenic colitis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Disease progression
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Fatigue
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Nodule
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Appendicitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Enterobacter sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Enterocolitis infectious
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lower respiratory tract infection bacterial
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Neutropenic sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0022 affected4 at risk
EG003
Sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lumbar puncture abnormal
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Tumour lysis syndrome
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Autonomic nervous system imbalance
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Neurotoxicity
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Polyneuropathy
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Subarachnoid haemorrhage
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Bipolar II disorder
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mental status changes
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Acute respiratory distress syndrome
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Rash generalised
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypotension
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pancytopenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Anaemia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Granulocytopenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lymphadenitis
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cardiogenic shock
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Myocardial infarction
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Tachyarrhythmia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Ventricular fibrillation
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Myocarditis
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mydriasis
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Upper gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Colitis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lower gastrointestinal haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pancreatitis acute
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Retroperitoneal haematoma
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Asthenia
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Death
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
General physical health deterioration
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Oedema
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sudden death
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cholecystitis
Hepatobiliary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Septic shock
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haemorrhage
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin toxicity
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pulmonary embolism
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Respiratory arrest
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Respiratory distress
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dyskinesia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Syncope
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Peripheral sensorimotor neuropathy
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Transient ischaemic attack
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Laboratory test abnormal
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Subdural haematoma
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Subarachnoid haemorrhage
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Splenic rupture
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Thoracic vertebral fracture
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Abscess
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Aspergillus infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cystitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Device related infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Escherichia urinary tract infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Infected dermal cyst
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Influenza
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lung infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Otitis media chronic
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pneumonia fungal
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pseudomembranous colitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Septic encephalopathy
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Urogenital infection bacterial
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Adenovirus infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Arthritis bacterial
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mycobacterium avium complex infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pneumocystis jirovecii pneumonia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pseudomonal sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypertension
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Abdominal infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Clostridial sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0011 affected6 at risk
EG0022 affected4 at risk
EG0031 affected3 at risk
EG0044 affected16 at risk
EG0051 affected6 at risk
EG00628 affected69 at risk
EG00737 affected84 at risk
EG00817 affected41 at risk
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Lymphadenitis
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0007 affected17 at risk
EG0010 affected6 at risk
EG0022 affected4 at risk
EG003
Spleen disorder
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Splenomegaly
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0006 affected17 at risk
EG0011 affected6 at risk
EG0022 affected4 at risk
EG003
Angina pectoris
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Diastolic dysfunction
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Ventricular tachycardia
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Adrenal insufficiency
Endocrine disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hypothyroidism
Endocrine disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Diplopia
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Eye haemorrhage
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Ocular hyperaemia
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Photophobia
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Scleral pigmentation
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Vision blurred
Eye disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0004 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Anal fissure
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Anal haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Angina bullosa haemorrhagica
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0007 affected17 at risk
EG0013 affected6 at risk
EG0022 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0008 affected17 at risk
EG0012 affected6 at risk
EG0022 affected4 at risk
EG003
Diverticulum
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0022 affected4 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gastritis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Haemorrhoidal haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hiatus hernia
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Megacolon
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mouth haemorrhage
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0006 affected17 at risk
EG0014 affected6 at risk
EG0024 affected4 at risk
EG003
Oral disorder
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Oral mucosal blistering
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Retching
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Tongue disorder
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Tooth loss
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Asthenia
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Catheter site pain
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Catheter site swelling
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Chest discomfort
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Chest pain
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Chills
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Fatigue
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0006 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Gait disturbance
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Generalised oedema
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hernia
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Influenza like illness
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Injection site pain
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Localised oedema
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mucosal inflammation
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Nodule
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Non-cardiac chest pain
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Oedema
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Oedema peripheral
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0005 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Pain
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Performance status decreased
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0005 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Thirst
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperbilirubinaemia
Hepatobiliary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Arthritis bacterial
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Bacteraemia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Bronchiolitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Candida infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Clostridium difficile infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Device related infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Enterobacter bacteraemia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Enterocolitis bacterial
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Enterocolitis infectious
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Fungal infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Genital infection viral
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Onychomycosis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Otitis media
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Pneumonia fungal
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pulmonary mycosis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sepsis
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Staphylococcal bacteraemia
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Staphylococcal infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Subcutaneous abscess
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Viral infection
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Infusion related reaction
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Post procedural haemorrhage
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Procedural headache
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Vascular access complication
Injury, poisoning and procedural complications
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Amylase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Blood fibrinogen decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Blood uric acid increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Chest X-ray abnormal
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Eastern Cooperative Oncology Group performance status worsened
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Karnofsky scale worsened
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lipase increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Liver function test increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Neutrophil count decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Platelet count decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Weight decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
White blood cell count decreased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hypermagnesaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hypernatraemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperphosphataemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypoalbuminaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Hypoglycaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0013 affected6 at risk
EG0021 affected4 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Hypophagia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Hypovolaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Metabolic acidosis
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Tumour lysis syndrome
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Vitamin D deficiency
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0011 affected6 at risk
EG0022 affected4 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Joint effusion
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0005 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Pain in jaw
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Periarthritis
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Plantar fasciitis
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Spinal pain
Musculoskeletal and connective tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Ageusia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Amnesia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Central nervous system lesion
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Cognitive disorder
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0021 affected4 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0004 affected17 at risk
EG0014 affected6 at risk
EG0021 affected4 at risk
EG003
Headache
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0003 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Lethargy
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Memory impairment
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Mental impairment
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Peroneal nerve palsy
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sedation
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Syncope
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Agitation
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Apathy
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Depressed mood
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Depression
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0022 affected4 at risk
EG003
Panic attack
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Proteinuria
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Renal cyst
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Vulvovaginal pruritus
Reproductive system and breast disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Atelectasis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0004 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Lung infiltration
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pleuritic pain
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Rhinitis allergic
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sinus congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Decubitus ulcer
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0021 affected4 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Ecchymosis
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Macule
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pain of skin
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Palmar erythema
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Panniculitis
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Plantar erythema
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pruritus allergic
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Purpura
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0002 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash macular
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash maculo-papular
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Rash papular
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0021 affected4 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Skin ulcer
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypertension
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0011 affected6 at risk
EG0020 affected4 at risk
EG003
Hypotension
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0012 affected6 at risk
EG0020 affected4 at risk
EG003
Ischaemia
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Phlebitis
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Thrombophlebitis
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Venous thrombosis
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0001 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Catheter site erythema
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Catheter site haemorrhage
General disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Weight increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Pallor
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Haematoma
Vascular disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Delirium
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hallucination
Psychiatric disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hiccups
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Sinus pain
Respiratory, thoracic and mediastinal disorders
MedDRA 21.1
Non-systematic Assessment
EG0000 affected17 at risk
EG0010 affected6 at risk
EG0020 affected4 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
2
OG0046
OG0056
0
OG0041
OG0050
Units
Counts
Participants
OG00069
Title
Denominators
Categories
Total participants
ParticipantsOG00069
Title
Measurements
OG00042.0(34.4 to 49.6)
Participants >= 55 years old
ParticipantsOG00060
Title
Measurements
OG00036.7(28.7 to 44.6)
Participants < 55 years old
ParticipantsOG0009
Title
Measurements
OG00077.8(60.0 to 95.5)
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00088
OG00144
Title
Denominators
Categories
Title
Measurements
OG0008.8(6.9 to 9.9)
OG0014.9(3.5 to 6.0)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Log Rank
0.0020
1-sided p-value from the log-rank test stratified by prognosis stratum according to Interactive Voice Response System (IVRS).
Hazard Ratio (HR)
0.569
2-Sided
80
0.441
0.734
Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.
Other
OG002
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG00023
OG0017
OG00222
Title
Denominators
Categories
Title
Measurements
OG0004.4(2.5 to 6.6)
OG00111.5(4.5 to 17.4)
OG00237.8(14.5 to NA)The upper bound of 80% CI was not estimable, as 10 (45.5%) participants were censored for no longer being followed for survival
Units
Counts
Participants
OG00069
Title
Denominators
Categories
Total participants
ParticipantsOG00069
Title
Measurements
OG00014.9(13.4 to 19.3)
Participants >= 55 years old
ParticipantsOG00060
Title
Measurements
OG00014.7(13.1 to 17.7)
Participants < 55 years old
ParticipantsOG0009
Title
Measurements
OG000NA(11.0 to NA)Number of deaths was 4 until the study completion, not enough for OS calculation.
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG00023
OG0017
OG00222
Title
Denominators
Categories
Title
Measurements
OG0008.7(2.3 to 21.5)
OG00128.6(7.9 to 59.6)
OG00254.5(38.9 to 69.5)
Participants
OG00088
OG00144
Title
Denominators
Categories
Title
Measurements
OG00018.2(12.9 to 23.5)
OG0012.3(0.0 to 5.2)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Cochran-Mantel-Haenszel
0.0112
Odds Ratio (OR)
4.2755
2-Sided
80
1.3057
13.9994
Based on the Cox proportional hazards model stratified by prognosis stratum according to IVRS.
Other
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00064
OG00178
OG00238
Title
Denominators
Categories
CRi
Title
Measurements
OG00010.9(6.2 to 17.7)
OG0015.1(2.3 to 10.0)
OG0022.6(0.3 to 9.9)
MLFS
Title
Measurements
OG0007.8(3.8 to 14.0)
OG0012.6(0.7 to 6.7)
OG0020.0(0.0 to 5.9)
PR
Title
Measurements
OG0001.6(0.2 to 5.9)
OG0016.4(3.2 to 11.6)
OG0022.6(0.3 to 9.9)
PRi
Title
Measurements
OG0001.6(0.2 to 5.9)
OG0011.3(0.1 to 4.9)
OG0020.0(0.0 to 5.9)
MR
Title
Measurements
OG00010.9(6.2 to 17.7)
OG0016.4(3.2 to 11.6)
OG00210.5(4.7 to 19.9)
SD
Title
Measurements
OG0006.3(2.8 to 12.1)
OG00116.7(11.3 to 23.4)
OG00221.1(12.7 to 31.9)
CRc
Title
Measurements
OG00035.9(27.9 to 44.7)
OG00111.5(7.1 to 17.6)
OG0020.0(0.0 to 5.9)
CRm
Title
Measurements
OG00037.5(29.4 to 46.2)
OG00116.7(11.3 to 23.4)
OG0022.6(0.3 to 9.9)
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG0005
OG00110
OG0026
Title
Denominators
Categories
mCR
Title
Measurements
OG0000.0(0.0 to 36.9)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
PR
Title
Measurements
OG0000.0(0.0 to 36.9)
OG0010.0(0.0 to 20.6)
OG0020.0(0.0 to 31.9)
SD
Title
Measurements
OG0000.0(0.0 to 36.9)
OG0010.0(0.0 to 20.6)
OG00233.3(9.3 to 66.7)
CRi
Title
Measurements
OG00020.0(2.1 to 58.4)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
Unconfirmed SD
Title
Measurements
OG0000.0(0.0 to 36.9)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
Unconfirmed CRi
Title
Measurements
OG0000.0(0.0 to 36.9)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
mCR (CRi not included)
Title
Measurements
OG0000.0(0.0 to 36.9)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
CRc
Title
Measurements
OG00060.0(24.7 to 88.8)
OG00110.0(1.0 to 33.7)
OG0020.0(0.0 to 31.9)
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG00013
ParticipantsOG0016
Title
Measurements
OG0001074± 63
OG0011942± 75
Cycle 1/Day 21
ParticipantsOG0008
ParticipantsOG0015
Title
Measurements
OG0001242± 56
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG00013
ParticipantsOG0016
Title
Measurements
OG0001.75(0.750 to 24.0)
OG0014.00(1.02 to 24.0)
Cycle 1/Day 21
ParticipantsOG0008
ParticipantsOG0015
Title
Measurements
OG0001.34(0.533 to 2.00)
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG00010
ParticipantsOG0014
Title
Measurements
OG00015020± 49
OG00128600± 17
Cycle 1/Day 21
ParticipantsOG0008
ParticipantsOG0014
Title
Measurements
OG00016660± 43
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG0001718± 28
OG0012381± 28
Cycle 2/Day 1
ParticipantsOG0003
ParticipantsOG0012
Title
Measurements
OG0001826± 44
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG0002.00(0.500 to 24.0)
OG0012.05(1.00 to 5.97)
Cycle 2/Day 1
ParticipantsOG0003
ParticipantsOG0012
Title
Measurements
OG0001.03(0.567 to 2.00)
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 10
ParticipantsOG0002
ParticipantsOG0013
Title
Measurements
OG000NA± NABased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 17700 and 26300 ng\*hr/mL.
OG00128380± 11
Cycle 2/Day 1
ParticipantsOG0003
ParticipantsOG0012
Title
Measurements
OG00017060± 29
OG001
Units
Counts
Participants
OG00016
OG0016
Title
Denominators
Categories
Induction Cycle 1/Day 3
ParticipantsOG00014
ParticipantsOG0016
Title
Measurements
OG000674.2± 45
OG0011622± 25
Induction Cycle 1/Day 10
ParticipantsOG00015
ParticipantsOG0016
Title
Measurements
OG0001135± 43
OG001
Units
Counts
Participants
OG00016
OG0016
Title
Denominators
Categories
Induction Cycle 1/Day 3
ParticipantsOG00014
ParticipantsOG0016
Title
Measurements
OG0005.99(0.467 to 25.2)
OG0016.00(1.00 to 6.07)
Induction Cycle 1/Day 10
ParticipantsOG00015
ParticipantsOG0016
Title
Measurements
OG0004.08(0.500 to 24.7)
OG001
Units
Counts
Participants
OG00016
OG0016
Title
Denominators
Categories
Induction Cycle 1/Day 3
ParticipantsOG00012
ParticipantsOG0015
Title
Measurements
OG0009332± 56
OG00122840± 43
Induction Cycle 1/Day 10
ParticipantsOG00013
ParticipantsOG0015
Title
Measurements
OG00016300± 46
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
LDAC Cycle 1/Day 2
ParticipantsOG00016
ParticipantsOG0016
Title
Measurements
OG00058.50± 58
OG001100.1± 29
LDAC Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG00063.01± 88
OG001
Ara-U Cycle 1/Day 2
ParticipantsOG00017
ParticipantsOG0016
Title
Measurements
OG000379.5± 34
OG001
Ara-U Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG000452.2± 36
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
LDAC Cycle 1/Day 2
ParticipantsOG00016
ParticipantsOG0016
Title
Measurements
OG0000.250(0.233 to 1.00)
OG0010.250(0.250 to 0.500)
LDAC Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG0000.325(0.233 to 1.00)
OG001
Ara-U Cycle 1/Day 2
ParticipantsOG00017
ParticipantsOG0016
Title
Measurements
OG0003.97(1.00 to 6.05)
OG001
Ara-U Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG0002.00(0.000 to 6.00)
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
LDAC Cycle 1/Day 2
ParticipantsOG00014
ParticipantsOG0016
Title
Measurements
OG00071.10± 28
OG00189.35± 28
LDAC Cycle 1/Day 10
ParticipantsOG0009
ParticipantsOG0015
Title
Measurements
OG00092.28± 25
OG001
Units
Counts
Participants
OG00017
OG0016
Title
Denominators
Categories
LDAC Cycle 1/Day 2
ParticipantsOG00016
ParticipantsOG0016
Title
Measurements
OG00062.55± 41
OG00187.49± 29
LDAC Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG00065.56± 76
OG001
Ara-U Cycle 1/Day 2
ParticipantsOG00017
ParticipantsOG0016
Title
Measurements
OG0002036± 36
OG001
Ara-U Cycle 1/Day 10
ParticipantsOG00012
ParticipantsOG0016
Title
Measurements
OG0002283± 43
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 1
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG000113.4± 59
OG001174.2± 113
Cycle 1/Day 2
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG000127.9± 43
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 1
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG0000.75(0.50 to 1.0)
OG0010.53(0.52 to 0.75)
Cycle 1/Day 2
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG0000.58(0.53 to 0.95)
OG001
Units
Counts
Participants
OG0004
OG0013
Title
Denominators
Categories
Cycle 1/Day 1
ParticipantsOG0003
ParticipantsOG0013
Title
Measurements
OG000133.4± 71
OG001251.5± 140
Cycle 1/Day 2
ParticipantsOG0002
ParticipantsOG0012
Title
Measurements
OG000NA± NABased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCinf values are 265 and 1040 ng\*hr/mL.
OG001
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Units
Counts
Participants
OG0009
OG0012
Title
Denominators
Categories
Cytarabine
Title
Measurements
OG0001070± 211
OG001NA± NABased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 276 and 879 ng\*hr/mL.
Ara-U
Title
Measurements
OG00028420± 32
OG001NA± NABased on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCtau values are 32430 and 45900 ng\*hr/mL.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Units
Counts
Participants
OG00015
OG0016
Title
Denominators
Categories
Daunorubicin
Title
Measurements
OG000275.3± 153
OG001341.0± 82
Daunorubicinol
Title
Measurements
OG000195.4± 139
OG001233.4± 46
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Units
Counts
Participants
OG00015
OG0016
Title
Denominators
Categories
Daunorubicin
Title
Measurements
OG0000.500(0.217 to 1.72)
OG0010.492(0.250 to 0.600)
Daunorubicinol
Title
Measurements
OG0001.00(0.217 to 5.90)
OG0010.642(0.283 to 4.00)
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
AML participants who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS participants who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response). Dauno is short for daunorubicin.
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
Units
Counts
Participants
OG0000
OG0019
OG0020
OG0031
OG00411
OG0051
Title
Denominators
Categories
CEBPA (CCAAT/enhancer-binding protein alpha)
Title
Measurements
OG0013
OG0030
OG0042
OG0050
DNMT3A (DNA [cytosine-5]-methyltransferase 3A)
Title
Measurements
OG0012
OG0030
OG0040
OG005
FLT3 (Fms-like tyrosine kinase 3)
Title
Measurements
OG0011
OG0030
OG0042
OG005
FLT3-ITD (FLT3 internal tandem duplications)
Title
Measurements
OG0010
OG0030
OG0041
OG005
IDH1 (Isocitrate dehydrogenase 1)
Title
Measurements
OG0011
OG0030
OG0040
OG005
IDH2 (Isocitrate dehydrogenase 2)
Title
Measurements
OG0010
OG0030
OG0042
OG005
KIT(Tyrosine-protein kinase Kit)
Title
Measurements
OG0010
OG0031
OG0040
OG005
KRAS(Kirsten rat sarcoma 2 viral oncogene homolog)
AML participants who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS participants who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response. Dauno is short for daunorubicin.
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
OG004
Phase 2 Unfit: LDAC Alone (Biomarker, Responder)
AML subjects who achieved CR, CRi, MLFS, PR, or PRi (AML investigator reported best overall response), and MDS subjects who achieved CR, mCR, PR, or SD (MDS investigator reported best overall response).
AML subjects who did not achieve CR, CRi, MLFS, PR, or PRi; and MDS subjects who did not achieve CR, mCR, PR or SD were defined as non-responders for best overall response.
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG00021
OG0017
OG00222
Title
Denominators
Categories
QTcF interval increase < 30 msec
Title
Measurements
OG00016
OG0012
OG00214
QTcF interval increase: 30 to < 60 msec
Title
Measurements
OG0005
OG0013
OG0026
QTcF interval increase >= 60 msec
Title
Measurements
OG0000
OG0012
OG0022
Maximum QTcF interval < 450 msec
Title
Measurements
OG00010
OG0014
OG00210
Maximum QTcF interval: 450 to < 480 msec
Title
Measurements
OG00011
OG0012
OG00210
Maximum QTcF interval: 480 to < 500 msec
Title
Measurements
OG0000
OG0010
OG0021
Maximum QTcF interval >= 500 msec
Title
Measurements
OG0000
OG0011
OG0021
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00068
OG00183
OG00217
Title
Denominators
Categories
QTcF interval increase < 30 msec
Title
Measurements
OG00041
OG00160
OG00212
QTcF interval increase: 30 to < 60 msec
Title
Measurements
OG00021
OG00119
OG0024
QTcF interval increase >= 60 msec
Title
Measurements
OG0006
OG0014
OG0021
Maximum QTcF interval < 450 msec
Title
Measurements
OG00046
OG00146
OG0028
Maximum QTcF interval: 450 to < 480 msec
Title
Measurements
OG00018
OG00129
OG0024
Maximum QTcF interval: 480 to < 500 msec
Title
Measurements
OG0003
OG0013
OG0023
Maximum QTcF interval >= 500 msec
Title
Measurements
OG0001
OG0015
OG0022
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG00023
OG0017
OG00222
Title
Denominators
Categories
Grade 1 AEs
Title
Measurements
OG0001
OG0011
OG0020
Grade 2 AEs
Title
Measurements
OG0002
OG0010
OG0023
Grade 3 AEs
Title
Measurements
OG0003
OG0011
OG0028
Grade 4 AEs
Title
Measurements
OG00010
OG0014
OG00210
Grade 5 AEs
Title
Measurements
OG0007
OG0011
OG0021
Missing or unknown AEs
Title
Measurements
OG0000
OG0010
OG0020
Phase 1B: Glasdegib + Cytarabine/Daunorubicin
Included all participants who received oral glasdegib in combination with cytarabine/daunorubicin in phase 1B portion.
Units
Counts
Participants
OG00023
OG0017
OG00222
Title
Denominators
Categories
Grade 1 AEs
Title
Measurements
OG0003
OG0012
OG0022
Grade 2 AEs
Title
Measurements
OG0002
OG0010
OG0027
Grade 3 AEs
Title
Measurements
OG0007
OG0010
OG0023
Grade 4 AEs
Title
Measurements
OG0006
OG0014
OG00210
Grade 5 AEs
Title
Measurements
OG0003
OG0010
OG0020
Missing or unknown AEs
Title
Measurements
OG0000
OG0010
OG0020
Participants received oral doses of glasdegib tablets 200 mg starting on Day 3 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28-day cycles. In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 2/Day 1 and Cycle 2/Day 16, respectively.
OG002
Phase 1B: Glasdegib 100 mg + Decitabine
Participants received oral doses of glasdegib tablets 100 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an intravenous (IV) infusion over 1 hour on Days 1-5 of the 28-day cycles.
OG003
Phase 1B: Glasdegib 200 mg + Decitabine
Participants received oral doses of glasdegib tablets 200 mg starting on Day 2 of Cycle 1 for PK assessment purposes and thereafter QD and continuously for 28-day cycles (starting on Day 1 for all other cycles). Decitabine was given at a dose of 20 mg/m^2 as an IV infusion over 1 hour on Days 1-5 of the 28-day cycles.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg. Participants who had glasdegib dose reduction were reported as the starting glasdegib dose level received. Two (2) participants in this cohort had dose reduction to 100 mg starting from Cycle 1/Day 24 and Cycle 5/Day 1, respectively.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 100 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.
Participants received 1-2 cycles of induction (glasdegib and daunorubicin/cytarabine), followed by 2-4 cycles of consolidation (glasdegib and high dose cytarabine) and a maximum of 6 cycles of maintenance (glasdegib alone). Daunorubicin was given on Days 1-3 QD at a dose of 60 mg/m^2/day by IV together with cytarabine on Days 1-7 at a dose of 100 mg/m^2/day by continuous IV infusion for each cycle of induction. Cytarabine was given on Days 1, 3, and 5 at a dose of 1 g/m^2 administered as a 3-hour IV infusion every 12 hours (2 g/m^2/day) for each cycle of consolidation. Glasdegib tablets 200 mg QD was started on induction Cycle 1/Day -3 and administered continuously QD thereafter for the duration of the study. A cycle was defined as 28 days.In March 2013, all active participants receiving glasdegib 200 mg were required to reduce dose to 100 mg.One (1) participant in this cohort had dose reduction to 100 mg starting from Consolidation Cycle 1/Day 21.
Units
Counts
Participants
OG00017
OG0016
OG0024
OG0033
OG00416
OG0056
Title
Denominators
Categories
AEs
Title
Measurements
OG00017
OG0016
OG0024
OG0033
OG00416
OG0056
SAEs
Title
Measurements
OG00013
OG0015
OG0024
OG003
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00069
OG00184
OG00241
Title
Denominators
Categories
Grade 1 AEs
Title
Measurements
OG0000
OG0012
OG0020
Grade 2 AEs
Title
Measurements
OG0001
OG0014
OG0021
Grade 3 AEs
Title
Measurements
OG00011
OG00115
OG0028
Grade 4 AEs
Title
Measurements
OG00052
OG00139
OG00215
Grade 5 AEs
Title
Measurements
OG0005
OG00124
OG00217
Missing or unknown AEs
Title
Measurements
OG0000
OG0010
OG0020
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00069
OG00184
OG00241
Title
Denominators
Categories
Grade 1 AEs
Title
Measurements
OG0000
OG0014
OG0024
Grade 2 AEs
Title
Measurements
OG0004
OG0019
OG0026
Grade 3 AEs
Title
Measurements
OG00015
OG00120
OG0023
Grade 4 AEs
Title
Measurements
OG00046
OG00134
OG00210
Grade 5 AEs
Title
Measurements
OG0001
OG0011
OG0021
Missing or unknown AEs
Title
Measurements
OG0000
OG0010
OG0020
OG001
Phase 2 Unfit: Glasdegib 100 mg + LDAC
Participants received oral doses of glasdegib tablets 100 mg QD in 28-day cycles on a continuous basis, starting on Day 1 of Cycle 1. LDAC was given at a dose of 20 mg subcutaneously BID on Days 1-10 of the 28 day cycles.
OG002
Phase 2 Unfit: LDAC Alone
Participants received LDAC subcutaneously at a dose of 20 mg BID on Days 1-10 of the 28 day cycles.
Units
Counts
Participants
OG00069
OG00184
OG00241
Title
Denominators
Categories
AEs
Title
Measurements
OG00069
OG00184
OG00241
SAEs
Title
Measurements
OG00035
OG00168
OG00232
1 affected
16 at risk
EG0051 affected6 at risk
EG00614 affected69 at risk
EG00724 affected84 at risk
EG0087 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0061 affected69 at risk
EG0070 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0072 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0071 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0071 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0062 affected69 at risk
EG00710 affected84 at risk
EG0085 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0073 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
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EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0073 affected84 at risk
EG0083 affected41 at risk
0 affected
3 at risk
EG0043 affected16 at risk
EG0051 affected6 at risk
EG00615 affected69 at risk
EG0073 affected84 at risk
EG0084 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0077 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0052 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0045 affected16 at risk
EG0050 affected6 at risk
EG00619 affected69 at risk
EG00710 affected84 at risk
EG0082 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0043 affected16 at risk
EG0052 affected6 at risk
EG0068 affected69 at risk
EG0077 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0042 affected16 at risk
EG0051 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0041 affected16 at risk
EG0052 affected6 at risk
EG00614 affected69 at risk
EG00718 affected84 at risk
EG0087 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0043 affected16 at risk
EG0052 affected6 at risk
EG00613 affected69 at risk
EG00721 affected84 at risk
EG00811 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0043 affected16 at risk
EG0051 affected6 at risk
EG00611 affected69 at risk
EG0077 affected84 at risk
EG0086 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0068 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0067 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0052 affected6 at risk
EG00612 affected69 at risk
EG0079 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0069 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0042 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0067 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
2 affected
3 at risk
EG0044 affected16 at risk
EG0052 affected6 at risk
EG00616 affected69 at risk
EG0079 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0042 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0042 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0077 affected84 at risk
EG0082 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0051 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0051 affected6 at risk
EG00611 affected69 at risk
EG0077 affected84 at risk
EG0084 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0044 affected16 at risk
EG0051 affected6 at risk
EG00610 affected69 at risk
EG0076 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0043 affected16 at risk
EG0051 affected6 at risk
EG00614 affected69 at risk
EG00711 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0043 affected16 at risk
EG0050 affected6 at risk
EG0069 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0051 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
1 affected
3 at risk
EG0043 affected16 at risk
EG0051 affected6 at risk
EG00612 affected69 at risk
EG0076 affected84 at risk
EG0081 affected41 at risk
0 affected
3 at risk
EG0044 affected16 at risk
EG0050 affected6 at risk
EG00614 affected69 at risk
EG00712 affected84 at risk
EG0084 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0083 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0066 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0073 affected84 at risk
EG0083 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0076 affected84 at risk
EG0086 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG00613 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0077 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0071 affected84 at risk
EG0083 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0075 affected84 at risk
EG0082 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0064 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0065 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0040 affected16 at risk
EG0050 affected6 at risk
EG0069 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
0 affected
3 at risk
EG0041 affected16 at risk
EG0050 affected6 at risk
EG0060 affected69 at risk
EG0070 affected84 at risk
EG0080 affected41 at risk
2577
± 104
4.00
(1.00 to 6.00)
31400
± 119
NA
± NA
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
NA
(NA to NA)
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
NA
± NA
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values.
2371
± 43
1.04
(0.583 to 4.12)
26370
± 39
132.5
± 39
569.7
± 29
652.0
± 27
0.250
(0.233 to 0.500)
4.00
(1.00 to 6.00)
1.99
(1.02 to 4.08)
143.9
± 24
134.8
± 26
3050
± 29
3528
± 29
121.7
± 37
0.53
(0.52 to 1.3)
NA
± NA
Based on pre-specified criteria, statistical analysis was not performed if fewer than 3 participants have reportable parameter values. Individual AUCinf values are 154 and 216 ng\*hr/mL.