Pharmacokinetic Guided Dose Escalation and Dose Confirmation With Oral Decitabine and Oral Cytidine Deaminase Inhibitor (CDAi) in Patients With Myelodysplastic Syndromes (MDS)
Official Title
A Phase1-2 Pharmacokinetic Guided Dose-Escalation and Dose-Confirmation Study of ASTX727, a Combination of the Oral Cytidine Deaminase Inhibitor (CDAi) E7727 With Oral Decitabine in Subjects With Myelodysplastic Syndromes (MDS)
Acronym
Not provided
Organization
Astex Pharmaceuticals, Inc.INDUSTRY
Status Module
Record Verification Date
Jul 2024
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
Oct 28, 2014Actual
Primary Completion Date
Jun 5, 2018Actual
Completion Date
Dec 4, 2019Actual
First Submitted Date
Mar 20, 2014
First Submission Date that Met QC Criteria
Apr 1, 2014
First Posted Date
Apr 4, 2014Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 4, 2020
Results First Submitted that Met QC Criteria
Oct 11, 2020
Results First Posted Date
Oct 19, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Oct 16, 2019
Certification/Extension First Submitted that Passed QC Review
Oct 16, 2019
Certification/Extension First Posted Date
Oct 23, 2019Actual
Last Update Submitted Date
Jul 31, 2024
Last Update Posted Date
Aug 27, 2024Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Astex Pharmaceuticals, Inc.INDUSTRY
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 first-in-human, 3-stage, open-label study evaluated the safety and pharmacokinetics of ASTX727, as well as determined the dose for later stages.
Detailed Description
The trial was designed to define daily doses of the individual components (cedazuridine [E7727] or decitabine) so that decitabine exposure after oral administration would be comparable to exposure after IV decitabine at the approved daily dose of 20 mg/m^2. The main objective of Phases 1 and 2 was to establish and confirm the doses of the 2 components to be used in the final fixed-dose combination (FDC) product (ASTX727) using mainly pharmacokinetics and pharmacodynamics as endpoints.
Conditions Module
Conditions
Myelodysplastic Syndrome
MDS
Keywords
Myelodysplastic Syndrome
MDS
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 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
130Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Phase 1 Dose Escalation
Experimental
Starting cohort was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Drug: ASTX727 Dose Escalation
Phase 2 Dose Confirmation
Experimental
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (E7727) (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Drug: ASTX727 Dose Confirmation
Phase 2 Fixed-Dose Combination
Experimental
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine (E7727)/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Drug: ASTX727 Fixed-Dose Combination
Interventions
Name
Type
Description
Arm Group Labels
Other Names
ASTX727 Dose Escalation
Drug
Oral investigational product and approved IV decitabine
Phase 1 Dose Escalation
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1
Mean AUC0-t of oral decitabine given with cedazuridine (E7727) following IV decitabine 20 mg/m^2 infusion on Day 5. AUCs were calculated by the linear up/log down method using the measured concentration-time values above the BQL (below the limit of quantification).
Day 5
Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2
Decitabine 5-day AUC ratio following IV decitabine 20 mg/m^2 infusion versus concomitant oral administration of decitabine + cedazuridine (E7727) or ASTX727 in the dose combination and fixed-dose combination stages, respectively. AUC0-t (the area under the concentration-time curve from time zero to the time of the last (tlast) quantifiable concentration (Ct)) by dose/cohort and course/days was used for estimating decitabine cumulative 5-day AUC0-t exposures.
Pre-dose to Day 5
Number of Participants With Dose-limiting Toxicity in Phase 1
Number of participants with protocol-specified dose-limiting toxicities (DLTs) in the dose escalation stage. DLTs were defined using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4.0), specifically ≥ Grade 3 non-hematologic toxicity (except Grade 3 nausea, vomiting, or diarrhea that is controllable by anti-emetics or optimal therapy or related to underlying disease or disease progression), specific Grade 3 laboratory tests, related prolonged Grade 4 thrombocytopenia or neutropenia that was not present prior to dosing, does not resolve within 14 days, and is not related to underlying disease, or any toxicity related to study treatment that results in treatment delays of >4 weeks after Day 28.
Up to Day 28 in Course 1 (28 days per course)
Mean Maximum %LINE Demethylation in Phase 2
Mean maximum % long interspread nuclear element-1 (LINE-1) demethylation after oral decitabine + cedazuridine (E7727) or ASTX727 (Course 1 or Course 2 - Treatment) compared with IV decitabine 20 mg/m^2 (Course 1 or Course 2 - IV Decitabine) in the dose confirmation and fixed-dose combination stages, respectively. Least squares mean of maximum %LINE-1 methylation change from baseline.
Secondary Outcomes
Measure
Description
Time Frame
Area Under the Concentration Versus Time Curve of Cedazuridine (E7727) and Cedazuridine-epimer
AUC is a measure of the plasma concentration of the drug over time (AUC0-8). PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
At specified timepoints from 0 to 24 hours post-dose
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
International Prognostic Scoring System (IPSS) low, intermediate -1, intermediate-2, or high risk MDS (including chronic myelomonocytic leukemia; CMML) in Dose Escalation and Dose Confirmation-Randomization; only intermediate-2, or high risk MDS in Dose Confirmation-Open Label
Eastern Cooperative Oncology Group (ECOG) 0 to 2
No major surgery within 2 weeks of starting study treatment
No cytotoxic chemotherapy within 2 weeks of starting study treatment
Able to swallow pills
Exclusion Criteria:
Previous treatment with 2 or more courses of decitabine (all stages) or azacitidine (Dose Confirmation stage only)
Treatment with investigational therapy within 2 weeks of study treatment
Uncontrolled medical disease(s) or active, uncontrolled infection
Response data for Phase 1 per June 2017 data cut and for Phase 2 per June 2018 data cut. Median follow up in Phase 1 was 1915.5 days (range: 1771-2213) and 1563.0 days in Phase 2 (range: 1199-1710).
Recruitment Details
In Phase 1, 127 participants were screened and 44 were randomized and received at least one treatment. In Phase 2, a total of 138 were screened, 86 were randomized, and 80 received at least one treatment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
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
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 6, 2017
Aug 4, 2020
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
Sequential Assignment
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
cedazuridine (E7727)
oral decitabine
IV decitabine
ASTX727 Dose Confirmation
Drug
Randomization cross over design for courses 1 and 2
Phase 2 Dose Confirmation
ASTX727 oral (combination of oral E7727 and oral decitabine)
IV decitabine
ASTX727 Fixed-Dose Combination
Drug
Fixed-dose investigational product
Phase 2 Fixed-Dose Combination
ASTX727 oral (combination of oral E7727 and oral decitabine)
Pre-dose to Day 28 in Course 2 (28 days per course)
Number of Participants With Overall Response in Phase 2
The evaluation of response was based on International Working Group (IWG) 2006 MDS Response Criteria, with overall response calculated as number of participants with complete response+partial response+marrow complete response+hematological improvement (CR+PR+mCR+HI).
Up to approximately 29 months
Maximum Observed Plasma Concentration (Cmax) of Cedazuridine (E7727) and Cedazuridine-epimer
Cmax is the maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
At specific timepoints from 0 to 24 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax) of Cedazuridine (E7727) and Cedazuridine-epimer
Tmax is the time to maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and the dose confirmation and fixed-dose combination stages in Phase 2.
At specific timepoints from 0 to 24 hours post-dose
Maximum Observed Plasma Concentration (Cmax) of Decitabine
Cmax is the maximum observed plasma concentration. PK parameters for plasma decitabine are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
At specific timepoints from 0 to 24 hours post-dose
Time to Maximum Observed Plasma Concentration (Tmax) of Decitabine in Phase 2
Tmax is the time to reach maximum plasma concentration for decitabine. PK parameters for plasma decitabine are reported for the dose confirmation and fixed-dose combination stages.
At specific timepoints from 0 to 24 hours post-dose
Duration of Complete Response in Phase 1
Duration of response (in number of days) was calculated from the first time the response was observed to time of relapse or last time point in the study.
Up to 32 Months
Duration of Complete Response in Phase 2 - Kaplan-Meier Estimate
Duration of response (in number of days) was calculated from the first time the response was observed to time of relapse or last time point in the study. Kaplan-Meier estimate for complete response is shown.
Up to approximately 29 months
Mean Maximum %LINE Demethylation in Phase 1
Mean maximum % long interspread nuclear element-1 (LINE-1) demethylation decrease from baseline after oral decitabine + cedazuridine (E7727) or ASTX727 compared with IV decitabine 20 mg/m^2 in the dose escalation stage.
Pre-dose to Day 28 in Course 2 (28 days per course)
Number of Participants With Overall Response in Phase 1
The evaluation of response was based on International Working Group 2006 MDS Response Criteria, with overall response calculated as number of participants with complete response+partial response+marrow complete response+hematological improvement (CR+PR+mCR+HI).
Up to 32 months
Number of Participants With Adverse Events
Number of participants with any treatment-emergent adverse event (AE) and any AE graded ≥3 using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Up to 5 years
Number of Participants With Hematological Improvement
Hematological improvement was calculated as defined by the IWG 2006 MDS Response Criteria.
Up to 32 months
Number of Participants With Transfusion Independence
Transfusion independence was calculated based on the number of transfusion-dependent participants at baseline who had no red blood cell or platelet transfusions for 56 consecutive days or more after treatment.
Up to 32 months
Number of Participants to Reach Acute Myeloid Leukemia (AML) or Death
Number of participants to reach the event (AML or death), where time to reach AML was calculated as the number of days from the day the participant received the first dose of IV decitabine, oral decitabine + E7727, or the FDC tablet to the date of death or the date of MDS progression to AML as defined by ≥20% blasts in bone marrow or peripheral blood using the World Health Organization classification. Time to AML or death was censored on the last date of contact if a participant was lost to follow up prior to reaching a time-to-event endpoint.
Up to 32 months
Number of Participants With Overall Survival
Overall survival was defined as the number of days from the day the participant received the first dose of IV decitabine, oral decitabine + E7727, or the FDC tablet to the date of death, regardless of cause.
Up to 32 months
Los Angeles
California
90024
United States
University of Chicago
Chicago
Illinois
60637
United States
Horizon Oncology
Lafayette
Indiana
47905
United States
Johns Hopkins
Baltimore
Maryland
21231
United States
Massachusetts General Hospital
Boston
Massachusetts
02114
United States
Dana Farber Cancer Institute
Boston
Massachusetts
02215
United States
John Theurer Cancer Center/ Hackensack University Medical Center
Hackensack
New Jersey
07601
United States
Roswell Park Cancer Institute
Buffalo
New York
14263
United States
Weill Cornell Medical College - New York Presbyterian Hospital
New York
New York
10021
United States
Vanderbilt Ingram Cancer Center
Nashville
Tennessee
37232
United States
M. D. Anderson
Houston
Texas
77030
United States
Medical College of Wisconsin
Milwaukee
Wisconsin
53226
United States
University of Alberta Hospital
Edmonton
Alberta
T6G 2G3
Canada
Sunnybrook Health Sciences Centre, Odette Cancer Centre
Toronto
Ontario
M4N 3M5
Canada
Princess Margaret Cancer Center
Toronto
Ontario
M5G 2M9
Canada
Hôpital Maisonneuve-Rosemont
Montreal
Quebec
H1T 2M4
Canada
Derived
Savona MR, Odenike O, Amrein PC, Steensma DP, DeZern AE, Michaelis LC, Faderl S, Harb W, Kantarjian H, Lowder J, Oganesian A, Azab M, Garcia-Manero G. An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: a multicentre, open-label, dose-escalation, phase 1 study. Lancet Haematol. 2019 Apr;6(4):e194-e203. doi: 10.1016/S2352-3026(19)30030-4.
FG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
FG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
FG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
FG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
FG005
Phase 2 Dose Confirmation Sequence A
Participants were randomized in a 1:1 ratio to receive oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) in Sequence A. In Courses ≥ 3, all participants received cedazuridine and decitabine Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
FG006
Phase 2 Dose Confirmation Sequence B
Participants were randomized in a 1:1 ratio to receive IV decibatine (20 mg/m^2) Dailyx5 in Course 1 followed by oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 2 (28 days per course) in Sequence B. In Courses ≥ 3, all participants received cedazuridine and decitabine Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
FG007
Phase 2 Fixed-Dose Combination Sequence A
Participants were randomized in a 1:1 ratio to receive oral cedazuridine (100 mg) + decitabine (35 mg) tablets Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) in Sequence A. In Courses ≥ 3, all participants received cedazuridine and decitabine Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
FG008
Phase 2 Fixed-Dose Combination Sequence B
Participants were randomized in a 1:1 ratio to receive IV decibatine (20 mg/m^2) Dailyx5 in Course 1 followed by oral cedazuridine (100 mg) + decitabine (35 mg) tablets Dailyx5 in Course 2 (28 days per course) in Sequence B. In Courses ≥ 3, all participants received cedazuridine and decitabine Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
FG0007 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG00419 subjects
FG00525 subjects
FG00625 subjects
FG00716 subjects
FG00814 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
NOT COMPLETED
FG0007 subjects
FG0016 subjects
FG0026 subjects
FG0036 subjects
FG00419 subjects
FG00525 subjects
FG00625 subjects
FG00716 subjects
FG00814 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0031 subjects
FG0042 subjects
FG0051 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
Death
FG0002 subjects
FG0012 subjects
FG0021 subjects
FG0031 subjects
FG004
Progressive Disease
FG0002 subjects
FG0011 subjects
FG0022 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0002 subjects
FG0010 subjects
FG0020 subjects
FG0034 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Other
FG0001 subjects
FG0013 subjects
FG0022 subjects
FG0030 subjects
FG004
Demographic and baseline characteristics are shown for participants who received at least one dose of study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
BG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
BG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
BG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
BG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
BG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
BG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
BG007
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0007
BG0016
BG0026
BG0036
BG00419
BG00550
BG00630
BG007124
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
BG00069.6± 8.1
BG00172± 6.2
BG00274± 4.8
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0004
BG0011
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Number
participants
Title
Denominators
Categories
Canada
Title
Measurements
BG0000
BG0010
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
Mean Decitabine Area Under the Concentration Versus Time Curve (AUC0-t) on Day 5 by Cohort in Phase 1
Mean AUC0-t of oral decitabine given with cedazuridine (E7727) following IV decitabine 20 mg/m^2 infusion on Day 5. AUCs were calculated by the linear up/log down method using the measured concentration-time values above the BQL (below the limit of quantification).
Participants who were successfully dosed according to criteria for both ASTX727 and IV decitabine dosing and with evaluable pharmacokinetic (PK) measurements are included.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
Day 5
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Units
Counts
Participants
OG0005
OG0016
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG00053.6± 40
OG00168.9± 44
OG00294.8± 46
OG003
Primary
Mean Decitabine Area Under the Plasma Concentration Versus Time Curve Ratio (5-day AUC0-t) in Phase 2
Decitabine 5-day AUC ratio following IV decitabine 20 mg/m^2 infusion versus concomitant oral administration of decitabine + cedazuridine (E7727) or ASTX727 in the dose combination and fixed-dose combination stages, respectively. AUC0-t (the area under the concentration-time curve from time zero to the time of the last (tlast) quantifiable concentration (Ct)) by dose/cohort and course/days was used for estimating decitabine cumulative 5-day AUC0-t exposures.
Participants with evaluable PK measurements are included. Phase 2 crossover design was used to compare AUC ratio for oral and IV administration.
Posted
Geometric Least Squares Mean
80% Confidence Interval
Ratio of Geometric LSM
Pre-dose to Day 5
ID
Title
Description
OG000
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either Sequence A: Oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2; or Sequence B: IV decitabine (20 mg/m^2) Dailyx5 in Course 1 followed by cedazuridine + decitabine capsules Dailyx5 in Course 2 (28 days per course). In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG001
Phase 2 Fixed-Dose Combination
Primary
Number of Participants With Dose-limiting Toxicity in Phase 1
Number of participants with protocol-specified dose-limiting toxicities (DLTs) in the dose escalation stage. DLTs were defined using the Common Terminology Criteria for Adverse Events Version 4.0 (CTCAEv4.0), specifically ≥ Grade 3 non-hematologic toxicity (except Grade 3 nausea, vomiting, or diarrhea that is controllable by anti-emetics or optimal therapy or related to underlying disease or disease progression), specific Grade 3 laboratory tests, related prolonged Grade 4 thrombocytopenia or neutropenia that was not present prior to dosing, does not resolve within 14 days, and is not related to underlying disease, or any toxicity related to study treatment that results in treatment delays of >4 weeks after Day 28.
The safety population includes participants in Phase 1 who received at least one dose of study drug.
Posted
Count of Participants
Participants
Up to Day 28 in Course 1 (28 days per course)
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Primary
Mean Maximum %LINE Demethylation in Phase 2
Mean maximum % long interspread nuclear element-1 (LINE-1) demethylation after oral decitabine + cedazuridine (E7727) or ASTX727 (Course 1 or Course 2 - Treatment) compared with IV decitabine 20 mg/m^2 (Course 1 or Course 2 - IV Decitabine) in the dose confirmation and fixed-dose combination stages, respectively. Least squares mean of maximum %LINE-1 methylation change from baseline.
The pharmacodynamic population includes all participants with evaluable data who received at least one dose of investigational product.
Posted
Least Squares Mean
95% Confidence Interval
Percent
Pre-dose to Day 28 in Course 2 (28 days per course)
ID
Title
Description
OG000
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG001
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Primary
Number of Participants With Overall Response in Phase 2
The evaluation of response was based on International Working Group (IWG) 2006 MDS Response Criteria, with overall response calculated as number of participants with complete response+partial response+marrow complete response+hematological improvement (CR+PR+mCR+HI).
The efficacy population includes all participants in Phase 2 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to approximately 29 months
ID
Title
Description
OG000
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG001
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Secondary
Area Under the Concentration Versus Time Curve of Cedazuridine (E7727) and Cedazuridine-epimer
AUC is a measure of the plasma concentration of the drug over time (AUC0-8). PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
Participants with evaluable PK measurements are included.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng*h/mL
At specified timepoints from 0 to 24 hours post-dose
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Secondary
Maximum Observed Plasma Concentration (Cmax) of Cedazuridine (E7727) and Cedazuridine-epimer
Cmax is the maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
Participants with evaluable PK measurements are included.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
At specific timepoints from 0 to 24 hours post-dose
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Cedazuridine (E7727) and Cedazuridine-epimer
Tmax is the time to maximum observed plasma concentration. PK parameters are reported for the dose escalation stage by cohort in Phase 1 and the dose confirmation and fixed-dose combination stages in Phase 2.
Participants with evaluable PK measurements are included.
Posted
Median
Full Range
hours
At specific timepoints from 0 to 24 hours post-dose
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Secondary
Maximum Observed Plasma Concentration (Cmax) of Decitabine
Cmax is the maximum observed plasma concentration. PK parameters for plasma decitabine are reported for the dose escalation stage by cohort in Phase 1 and dose confirmation and fixed-dose combination stages in Phase 2.
Participants with evaluable PK measurements are included.
Posted
Geometric Mean
Geometric Coefficient of Variation
ng/mL
At specific timepoints from 0 to 24 hours post-dose
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Secondary
Time to Maximum Observed Plasma Concentration (Tmax) of Decitabine in Phase 2
Tmax is the time to reach maximum plasma concentration for decitabine. PK parameters for plasma decitabine are reported for the dose confirmation and fixed-dose combination stages.
Participants with evaluable PK measurements are included.
Posted
Median
Full Range
hours
At specific timepoints from 0 to 24 hours post-dose
ID
Title
Description
OG000
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG001
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Secondary
Duration of Complete Response in Phase 1
Duration of response (in number of days) was calculated from the first time the response was observed to time of relapse or last time point in the study.
The efficacy population includes all participants in Phase 1 who received at least one dose of investigational product.
Posted
Median
Full Range
days
Up to 32 Months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Phase 1 Dose Escalation Cohort 3
Secondary
Duration of Complete Response in Phase 2 - Kaplan-Meier Estimate
Duration of response (in number of days) was calculated from the first time the response was observed to time of relapse or last time point in the study. Kaplan-Meier estimate for complete response is shown.
The efficacy population includes all participants in Phase 2 who received at least one dose of investigational product.
Posted
Median
95% Confidence Interval
days
Up to approximately 29 months
ID
Title
Description
OG000
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG001
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Secondary
Mean Maximum %LINE Demethylation in Phase 1
Mean maximum % long interspread nuclear element-1 (LINE-1) demethylation decrease from baseline after oral decitabine + cedazuridine (E7727) or ASTX727 compared with IV decitabine 20 mg/m^2 in the dose escalation stage.
The pharmacodynamic population includes all participants in Phase 1 with evaluable data who received at least one dose of investigational product.
Posted
Mean
Standard Deviation
Percent change
Pre-dose to Day 28 in Course 2 (28 days per course)
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Secondary
Number of Participants With Overall Response in Phase 1
The evaluation of response was based on International Working Group 2006 MDS Response Criteria, with overall response calculated as number of participants with complete response+partial response+marrow complete response+hematological improvement (CR+PR+mCR+HI).
The efficacy population includes all participants in Phase 1 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to 32 months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Secondary
Number of Participants With Adverse Events
Number of participants with any treatment-emergent adverse event (AE) and any AE graded ≥3 using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
The safety population includes all participants in Phase 1 and Phase 2 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to 5 years
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Phase 1 Dose Escalation Cohort 3
Secondary
Number of Participants With Hematological Improvement
Hematological improvement was calculated as defined by the IWG 2006 MDS Response Criteria.
The efficacy population includes all participants in Phase 1 and Phase 2 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to 32 months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation: Oral investigational product and approved IV decitabine
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation: Oral investigational product and approved IV decitabine
Secondary
Number of Participants With Transfusion Independence
Transfusion independence was calculated based on the number of transfusion-dependent participants at baseline who had no red blood cell or platelet transfusions for 56 consecutive days or more after treatment.
The efficacy population includes all participants in Phase 1 and Phase 2 who received at least one dose of investigational product and were transfusion-dependent at baseline. Number analyzed is the number of participants who were transfusion-dependent at baseline.
Posted
Count of Participants
Participants
Up to 32 months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Secondary
Number of Participants to Reach Acute Myeloid Leukemia (AML) or Death
Number of participants to reach the event (AML or death), where time to reach AML was calculated as the number of days from the day the participant received the first dose of IV decitabine, oral decitabine + E7727, or the FDC tablet to the date of death or the date of MDS progression to AML as defined by ≥20% blasts in bone marrow or peripheral blood using the World Health Organization classification. Time to AML or death was censored on the last date of contact if a participant was lost to follow up prior to reaching a time-to-event endpoint.
The efficacy population includes all participants in Phase 1 and Phase 2 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to 32 months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Starting cohort was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Starting cohort was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Secondary
Number of Participants With Overall Survival
Overall survival was defined as the number of days from the day the participant received the first dose of IV decitabine, oral decitabine + E7727, or the FDC tablet to the date of death, regardless of cause.
The efficacy population includes all participants in Phase 1 and Phase 2 who received at least one dose of investigational product.
Posted
Count of Participants
Participants
Up to 32 months
ID
Title
Description
OG000
Phase 1 Dose Escalation Cohort 1
Starting cohort was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG001
Phase 1 Dose Escalation Cohort 2
Starting cohort was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Time Frame
Up to 5 years
Description
Treatment-emergent adverse events were recorded from the start of study treatment until 30 days after the last dose of study treatment.
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 1 Dose Escalation Cohort 1
Cohort 1 was administered 40 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
2
7
2
7
6
7
EG001
Phase 1 Dose Escalation Cohort 2
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
2
6
4
6
6
6
EG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
1
6
2
6
6
6
EG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
1
6
6
6
6
6
EG004
Phase 1 Dose Escalation Cohort 5
Cohort 1 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
5
19
14
19
18
19
EG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
29
50
39
50
48
50
EG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
21
30
25
30
30
30
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0005 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG0038 events2 affected6 at risk
EG004
Anemia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cardiogenic shock
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Myocarditis
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastrointestinal hemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Large intestinal obstruction
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Malena
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pancreatitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Edema peripheral
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Multiple organ dysfunction syndrome
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sudden death
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bacteremia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Atypical mycobacterial infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Respiratory syncytial virus infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cervical vertebral fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Facial bones fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Upper limb fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Liver function test increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Failure to thrive
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vertebral artery dissection
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Acute kidney injury
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Septic shock
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bacterial infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Endocarditis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Escherichia infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Subcutaneous abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gout
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bursitis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Joint stiffness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Musculoskeletal stiffness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Small cell lung cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Syncope
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cerebrovascular accident
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Seizure
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Mental status change
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tachypnea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dyspnea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Acute febrile neutrophilic dermatosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Peripheral ischemia
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypertension
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Anal fissure
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Atypical pneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Anal abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pyomyositis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Soft tissue infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Subdural hemorrhage
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Large intestine perforation
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oral infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Squamous cell carcinoma of the tongue
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alpha hemolytic streptococcal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Perirectal abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG00016 events4 affected7 at risk
EG0014 events3 affected6 at risk
EG00211 events4 affected6 at risk
EG0037 events3 affected6 at risk
EG00434 events10 affected19 at risk
EG00567 events27 affected50 at risk
EG00659 events15 affected30 at risk
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG00013 events3 affected7 at risk
EG00112 events2 affected6 at risk
EG0024 events4 affected6 at risk
EG003
Anemia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0008 events4 affected7 at risk
EG0011 events1 affected6 at risk
EG0022 events2 affected6 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0006 events1 affected7 at risk
EG0016 events2 affected6 at risk
EG0022 events1 affected6 at risk
EG003
Lymphadenopathy
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Thrombocytosis
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bradycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cerumen impaction
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diplopia
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Dry eye
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Eye irritation
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Eye pruritus
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vision blurred
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vitreous floaters
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Conjunctival hemorrhage
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events2 affected7 at risk
EG0015 events5 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0014 events4 affected6 at risk
EG0023 events3 affected6 at risk
EG003
Diarrhea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0003 events2 affected7 at risk
EG0012 events1 affected6 at risk
EG0023 events2 affected6 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Hemorrhoids
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Mouth ulceration
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0022 events1 affected6 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0022 events1 affected6 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Rectal hemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ascites
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Duodenitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastroesophageal reflux disease
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Inguinal hernia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Lip dry
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Lower gastrointestinal hemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pancreatic cyst
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Periodontal disease
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tongue ulceration
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fatigue
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0004 events2 affected7 at risk
EG0017 events5 affected6 at risk
EG0024 events3 affected6 at risk
EG003
Edema peripheral
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0014 events3 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events2 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Edema
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0022 events2 affected6 at risk
EG003
Pain
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chills
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Catheter site erythema
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Chest discomfort
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Generalized edema
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Peripheral swelling
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Atypical mycobacterial infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bronchitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Device related infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Diverticulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Eye infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Furuncle
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Heliobacter infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Laryngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Oral herpes
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Otitis externa
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rash pustular
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Subcutaneous abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Vaginal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Laceration
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthropod bite
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Iliotibial band syndrome
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Ligament sprain
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Skin abrasion
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Subdural hematoma
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Transfusion reaction
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0003 events1 affected7 at risk
EG0012 events1 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Weight decreased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0004 events1 affected7 at risk
EG0013 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0004 events2 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood alkaline phosphatase increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Alanine aminotransferase decreased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Blood urea increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Electrocardiogram repolarization abnormality
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Weight increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypomagnesemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0003 events2 affected7 at risk
EG0011 events1 affected6 at risk
EG0025 events1 affected6 at risk
EG003
Hypoalbuminemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0003 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypokalemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0003 events2 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyponatremia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0012 events2 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypernatremia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperphosphatemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0022 events1 affected6 at risk
EG003
Hypocalcemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperglycemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hyperuricemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Hypophosphatemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events2 affected7 at risk
EG0010 events0 affected6 at risk
EG0021 events1 affected6 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0011 events1 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Arthritis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Joint swelling
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 events1 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Muscle tightness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Basal cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 events0 affected7 at risk
EG0010 events0 affected6 at risk
EG0020 events0 affected6 at risk
EG003
Squamous cell carcinoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG00040
OG00124
Title
Denominators
Categories
Title
Measurements
OG00093.52(82.10 to 106.50)
OG00197.59(80.48 to 118.30)
Cohort 2 was administered 60 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0041
Units
Counts
Participants
OG00048
OG00130
Title
Denominators
Categories
Course 1 - Treatment
ParticipantsOG00024
ParticipantsOG00116
Title
Measurements
OG00011.159(9.023 to 13.294)
OG00110.077(7.696 to 12.459)
Course 1 - IV Decitabine
ParticipantsOG00024
ParticipantsOG00114
Title
Measurements
OG00011.303(9.167 to 13.439)
OG001
Course 2 - Treatment
ParticipantsOG00022
ParticipantsOG0019
Title
Measurements
OG0009.833(7.446 to 12.219)
OG001
Course 2 - IV Decitabine
ParticipantsOG00022
ParticipantsOG00111
Title
Measurements
OG0009.920(7.534 to 12.307)
OG001
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
Mean Difference (Final Values)
-0.144
2-Sided
95
-3.165
2.876
Course 1
Equivalence
The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
OG000
Mean Difference (Final Values)
-0.087
2-Sided
95
-3.463
3.288
Course 2
Equivalence
The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
OG001
Mean Difference (Final Values)
-2.588
2-Sided
95
-6.074
0.899
Course 1
Equivalence
The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
OG001
Mean Difference (Final Values)
-0.096
2-Sided
95
-5.080
4.888
Course 2
Equivalence
The 95% confidence intervals for the difference (oral - IV) were generated using an ANOVA model separately for Course 1 and Course 2.
Units
Counts
Participants
OG00050
OG00130
Title
Denominators
Categories
Title
Measurements
OG00029
OG00119
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG00419
OG00537
OG00619
Title
Denominators
Categories
Cedazuridine
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG00419
ParticipantsOG00532
ParticipantsOG00614
Title
Measurements
OG0001650± 43
OG0011990± 64
OG0023190± 53
OG003
Cedazuridine-epimer
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0025
ParticipantsOG0033
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG00419
OG00547
OG00629
Title
Denominators
Categories
Cedazuridine
Title
Measurements
OG000309± 50
OG001376± 67
OG002636± 50
OG003697± 75
OG004570± 51
OG005451± 51.4
OG006293± 43.1
Cedazuridine-epimer
Title
Measurements
OG00096± 22
OG001184± 70
OG002343± 44
OG003
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG00419
OG00547
OG00630
Title
Denominators
Categories
Cedazuridine
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
ParticipantsOG00419
ParticipantsOG00547
ParticipantsOG00629
Title
Measurements
OG0003(2 to 4)
OG0013(2 to 4)
OG0023(3 to 4)
OG003
Cedazuridine-epimer
ParticipantsOG0006
ParticipantsOG0016
ParticipantsOG0026
ParticipantsOG0036
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG00419
OG00547
OG00629
Title
Denominators
Categories
Title
Measurements
OG00054.0± 36
OG00176.5± 42
OG00280.9± 41
OG003161± 51
OG004138± 55
OG005126± 70.9
OG006126± 76.2
Units
Counts
Participants
OG00049
OG00129
Title
Denominators
Categories
Title
Measurements
OG0001.00(0.47 to 3.00)
OG0010.95(0.47 to 2.12)
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
Title
Denominators
Categories
Title
Measurements
OG000546.00(546.0 to 546.0)
OG001364.00(56.0 to 672.0)
OG002470.00(470.0 to 470.0)
OG00329.00(29.0 to 29.0)
OG004399.0(202.0 to 420.0)
Units
Counts
Participants
OG00050
OG00130
Title
Denominators
Categories
Title
Measurements
OG000413.0(180.0 to 553.0)
OG001155.0(35.0 to 285.0)
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Units
Counts
Participants
OG0006
OG0016
OG0026
OG0036
OG00418
Title
Denominators
Categories
Course 1
Title
Measurements
OG000-8.3± 5.28
OG001-9.2± 5.84
OG002-10.5± 7.55
OG003-12.1± 7.82
OG004-11.7± 5.67
Course 2
Title
Measurements
OG000-8.0± 3.56
OG001-7.1± 2.92
OG002-8.9± 5.42
OG003
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
Title
Denominators
Categories
Title
Measurements
OG0004
OG0013
OG0022
OG0031
OG0043
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
OG00550
OG00630
Title
Denominators
Categories
Any Adverse Event
Title
Measurements
OG0006
OG0016
OG0026
OG0036
OG00419
OG00550
OG00630
Any Grade ≥3 Adverse Event
Title
Measurements
OG0005
OG0016
OG0025
OG003
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation: Oral investigational product and approved IV decitabine
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation: Oral investigational product and approved IV decitabine
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 5 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
ASTX727 Dose Escalation: Oral investigational product and approved IV decitabine
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
OG00550
OG00630
Title
Denominators
Categories
Title
Measurements
OG0004
OG0013
OG0022
OG0030
OG0043
OG0058
OG0067
OG002
Phase 1 Dose Escalation Cohort 3
Cohort 3 was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Cohort 4 was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Cohort 1 was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0004
OG0012
OG0026
OG0035
OG00412
OG00529
OG00621
Title
Denominators
Categories
Red Blood Cell
ParticipantsOG0004
ParticipantsOG0012
ParticipantsOG0025
ParticipantsOG0034
ParticipantsOG0048
ParticipantsOG00522
ParticipantsOG00616
Title
Measurements
OG0002
OG0010
OG0023
OG003
Platelet
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0021
ParticipantsOG0031
OG002
Phase 1 Dose Escalation Cohort 3
Starting cohort was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Starting cohort was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Starting cohort was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
Units
Counts
Participants
OG0007
OG0016
OG0026
OG0036
OG00419
OG00550
OG00630
Title
Denominators
Categories
Title
Measurements
Censored
OG0004
OG0015
OG0026
OG0035
OG00411
OG00522
OG00611
Event
OG0003
OG0011
OG0020
OG0031
OG004
Phase 1 Dose Escalation Cohort 3
Starting cohort was administered 100 mg oral cedazuridine and 20 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG003
Phase 1 Dose Escalation Cohort 4
Starting cohort was administered 100 mg oral cedazuridine and 40 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG004
Phase 1 Dose Escalation Cohort 5
Starting cohort was administered 100 mg oral cedazuridine and 30 mg oral decitabine. Participants were enrolled into successive cohorts in which either the cedazuridine or decitabine oral dose was varied in Course 1 Day 2 through Course 1 Day 5 for comparison with a single dose of IV decitabine at 20 mg/m^2 administered on Day 1 by continuous IV infusion over 1 hour (28 days per course).
OG005
Phase 2 Dose Confirmation
Participants were randomized in a 1:1 ratio to receive either oral cedazuridine (100 mg) + decitabine (35 mg) capsules Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received cedazuridine and decitabine capsules Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.
OG006
Phase 2 Fixed-Dose Combination
Participants were randomized in a 1:1 ratio to receive either the fixed-dose combination (FDC) tablet (100 mg cedazuridine/35 mg decitabine) Dailyx5 in Course 1 followed by IV decitabine (20 mg/m^2) Dailyx5 in Course 2 (28 days per course) or the converse. In Courses ≥ 3, all participants received the FDC tablet Dailyx5 in 28-day courses until disease progression, unacceptable toxicity, withdrawal of consent or withdrawal from the study.