A Dose-finding Study of the Bromodomain (Brd) Inhibitor O... | NCT01713582 | Trialant
NCT01713582
Sponsor
Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Status
Completed
Last Update Posted
Jan 26, 2021Actual
Enrollment
141Actual
Phase
Phase 1
Conditions
Acute Myeloid Leukemia
Diffuse Large B-cell Lymphoma
Acute Lymphoblastic Leukemia
Multiple Myeloma
Interventions
OTX015/Birabresib
Countries
Not provided
Protocol Section
Identification Module
NCT ID
NCT01713582
Obsolete or Duplicate NCT IDs
NCT02542358
Organization Study
8628-001
Secondary IDs
ID
Type
Description
Link
OTX015_104
Other Identifier
OncoEthix Protocol Number
2012-003380-22
EudraCT Number
MK-8628-001
Other Identifier
Merck Protocol Number
Brief Title
A Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/ Birabresib (MK-8628) in Hematologic Malignancies (MK-8628-001)
Official Title
A Phase I, Dose-finding Study of the Bromodomain (Brd) Inhibitor OTX015/MK-8628 in Haematological Malignancies
Acronym
Not provided
Organization
Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)INDUSTRY
Status Module
Record Verification Date
Jan 2021
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
Dec 14, 2012Actual
Primary Completion Date
Jan 20, 2017Actual
Completion Date
Jan 20, 2017Actual
First Submitted Date
Oct 22, 2012
First Submission Date that Met QC Criteria
Oct 22, 2012
First Posted Date
Oct 24, 2012Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 11, 2018
Results First Submitted that Met QC Criteria
Feb 7, 2018
Results First Posted Date
Oct 1, 2018Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Jan 7, 2021
Last Update Posted Date
Jan 26, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Oncoethix GmbH, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
No
Is FDA Regulated Device
No
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
The primary purpose of this study was to determine the recommended dose (RD) of birabresib (MK-8628) /OTX015 for further phase II studies, in participants with acute leukemia (AL) including acute myeloid leukemia (AML; de novo and secondary to a myelodysplastic syndrome) and acute lymphoblastic leukemia (ALL) or other hematologic malignancies (OHM) including diffuse large B cell lymphoma (DLBCL) and multiple myeloma (MM). The first phase of the study will be a dose escalation phase to determine the Phase II RD using dose-limiting toxicities (DLTs). Once the RD is determined, participants will be enrolled in an expansion phase at the RD to determine preliminary efficacy in AL and OHM cohorts. Participants received therapy in 21-day cycles until disease progression, intolerable toxicity, or treatment interruption for >2 weeks due to toxicity.
Detailed Description
Not provided
Conditions Module
Conditions
Acute Myeloid Leukemia
Diffuse Large B-cell Lymphoma
Acute Lymphoblastic Leukemia
Multiple Myeloma
Keywords
Not provided
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 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
141Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
AL 10 mg QD 14-21
Experimental
Participants received 10 mg birabresib/OTX015 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 20 mg QD 14-21
Experimental
Participants received 20 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 40 mg QD 14-21
Experimental
Participants received 40 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 20 mg BID 21-21
Experimental
Participants received 20 mg birabresib/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 80 mg QD 14-21
Experimental
Participants received 80 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.02 and defined as any of the following: grade 3 or 4 non-hematologic adverse events unless they were not optimally treated with supportive care; grade 3 or 4 asymptomatic laboratory abnormal values lasting >7 days; prolonged grade 2 toxicity (lasting more than 2 weeks) leading to treatment interruption and/or dose reduction; pancytopenia with a hypocellular bone marrow and no marrow blasts lasting ≥6 weeks (AL participants); grade 3 neutropenia with fever or infection (OHM participants); grade 3 thrombocytopenia with bleeding (OHM participants); or grade 4 neutropenia or thrombocytopenia, regardless of symptoms and lasting ≥3 days (OHM participants).
Cycle 1 (Up to 21 days)
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants Who Experienced at Least One Adverse Event (AE)
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. AEs were collected during the entire time frame of treatment plus up to 40 days of follow-up.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Histologically or cytologically proven acute leukemias (AML or ALL) or hematologic malignancies (DLBCL or MM) using standard diagnosis criteria. Acute leukemia includes de novo and secondary to a pre-existing myelodysplastic syndrome, according to the World Health Organization 2008 classification. For DLBCL, an archived formaldehyde-fixed paraffin-embedded block must be available.
Has failed all standard therapies or for whom standard treatments are contra-indicated:
Acute leukemia participants: <60 years old in second relapse or relapsing after allogeneic stem cell transplantation (aSCT) regardless of number of relapses; >60 years old in first relapse with a disease-free interval (DFI) <12 months or further relapse; irrespective of age, in participants relapsing after aSCT, the time elapsed since aSCT should be >90 days; participants with B-cell ALL: Philadelphia chromosome positive (Ph+) must have received ≥2 lines of therapy, including 2 bcr-abl tyrosine-kinase (TK) inhibitors (among imatinib, nilotinib and dasatinib), or only 1 line including 1 TK inhibitor, if the relapse/refractoriness is associated with the detection of a resistance mutation to these inhibitors
DLBCL participants: Failed 2 standard lines of therapy (≥1 containing an anti-CD20 monoclonal antibody), or for whom such treatment is contra-indicated
MM participants: Adequately exposed to at least one alkylating agent, one corticosteroid, one immunomodulatory drug (IMiD) and bortezomib, or for whom such treatments are contra-indicated.
For participants with evaluable disease:
Advanced leukemia participants must have >5% bone marrow blasts at study entry, without alternative causality (e.g. bone marrow regeneration)
DLBCL participants must have ≥1 non-irradiated tumor mass ≥15 mm (long axis of lymph node) or ≥10 mm (short axis of lymph node or extranodal lesions) on spiral computed tomography (CT)-scan.
MM participants must have ≥1 of the following: serum monoclonal component >1 g/dL (IgG), or >0.5 g/dL (IgA), or Bence-Jones (BJ) proteinuria >200 mg/24h, or measurable plasmacytoma (not previously irradiated).
Life expectancy ≥3 months.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Off previous therapy ≥3 weeks prior to first study drug administration with full recovery from any previous toxicities, except 1) hydroxyurea single agent of in combination (e.g. + 6-Mercaptopurine [6MP]) to control hyperleukocytosis, which should be stopped for ≥48 hours, and 2) rituximab, which should be stopped for ≥3 weeks.
Recovery from the non-hematologic toxic effects of prior treatment to grade ≤1, according to National Cancer Institute Common Toxicity Criteria (NCI-CTC) classification, except alopecia.
Adequate bone marrow function.
Adequate calculated creatinine clearance.
Adequate liver function tests.
Complete baseline disease assessment workup prior to first study drug administration.
Exclusion Criteria:
History of prior malignancy other than those previously treated with a curative intent >3 years ago and without relapse (any tumor) or basal cell skin cancer, in situ cervical cancer, superficial bladder cancer, or high grade intestinal polyps treated adequately, regardless of the DFI.
Pregnant or lactating women or women of childbearing potential not using adequate contraception. Male participants not using adequate contraception.
Peripheral cytopenias (i.e. auto-immune hemolytic anemia or thrombocytopenia).
Acute promyelocytic leukemia or with clinically uncontrolled (i.e. with bleeding) disseminated intravascular coagulation (DIC).
Chronic graft versus host disease (GVHD) or on immunosuppressive therapy for the control of GVHD.
Uncontrolled leptomeningeal disease.
Other tumor location necessitating an urgent therapeutic intervention (palliative care, surgery or radiation therapy), such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.
Unable to swallow oral medications, or has gastrointestinal condition (e.g. malabsorption, resection) deemed to jeopardize intestinal absorption.
Other serious illness or medical conditions, which, in the investigator's opinion could hamper understanding of the study by the participants, participant's compliance to study treatment, participant's safety or interpretation of study results. These conditions include (but are not restricted to):
Congestive heart failure or angina pectoris except if medically controlled. Previous history of myocardial infarction within 1 year of study entry, uncontrolled hypertension or arrhythmias.
Existence of significant neurologic or psychiatric disorders impairing the ability to obtain consent.
Uncontrolled infection.
Known human immunodeficiency virus (HIV) positivity
Concurrent treatment with other experimental therapies or participation in another clinical trial within 30 days prior to first study drug administration.
Concurrent treatment or treatment within 30 days prior to first study drug administration with any other anticancer therapy, except hydroxyurea (+/- 6MP) to control hyperleukocytosis.
Concomitant treatment with corticosteroids except if chronic treatment with ≤30 mg of methylprednisolone daily or equivalent dose of other corticosteroids.
Odore E, Lokiec F, Cvitkovic E, Bekradda M, Herait P, Bourdel F, Kahatt C, Raffoux E, Stathis A, Thieblemont C, Quesnel B, Cunningham D, Riveiro ME, Rezai K. Phase I Population Pharmacokinetic Assessment of the Oral Bromodomain Inhibitor OTX015 in Patients with Haematologic Malignancies. Clin Pharmacokinet. 2016 Mar;55(3):397-405. doi: 10.1007/s40262-015-0327-6.
The study consisted of a dose escalation phase in participants with AL and OHM followed by and expansion phase in 3 cohorts: de novo acute myelocytic leukemia (AML), myelodysplastic syndrome (MDS) AML, and diffuse large B-cell lymphoma (DLBCL).
Recruitment Details
80 participants were enrolled in the acute leukemia (AL) cohort and 78 were treated. 61 participants were enrolled in the other hematological malignancies (OHM) cohort and 60 were treated.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 14 of a 21-day cycle.
FG001
AL 20 mg QD 14-21
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
0
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
SAP
No
Yes
No
Statistical Analysis Plan
Mar 10, 2017
Feb 7, 2018
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Canada
France
Italy
Switzerland
United Kingdom
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Non-Randomized
Intervention Model
Parallel 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
AL 40 mg BID 14-21
Experimental
Participants received 40 mg birabresib/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 120 mg QD 14-21
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 120 mg QD 21-21
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 160 mg QD 14-21
Experimental
Participants received 160 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AML de novo 80 mg QD 14-21
Experimental
Participants received 80 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AML/MDS 80 mg QD 14-21
Experimental
Participants received 80 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 10 mg QD 21-21
Experimental
Participants received 10 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 20 mg QD 21-21
Experimental
Participants received 20 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 40 mg QD 21-21
Experimental
Participants received 40 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 80 mg QD 21-21
Experimental
Participants received 80 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 40 mg BID 21-21
Experimental
Participants received 40 mg birabresib/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 120 mg QD 21-21
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 120 mg QD 14-21
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
OHM 120 mg QD 5-7
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 5 of a 7-day cycle.
Drug: OTX015/Birabresib
OHM 120 mg QD 7-21
Experimental
Participants received 120 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 7 of a 21-day cycle
Drug: OTX015/Birabresib
OHM/DLBCL 80 mg QD 14-21
Experimental
Participants received 80 mg birabresib/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
Drug: OTX015/Birabresib
AL 160 mg QD 14-21
AL 20 mg BID 21-21
AL 20 mg QD 14-21
AL 40 mg BID 14-21
AL 40 mg QD 14-21
AL 80 mg QD 14-21
AML de novo 80 mg QD 14-21
AML/MDS 80 mg QD 14-21
OHM 10 mg QD 21-21
OHM 120 mg QD 14-21
OHM 120 mg QD 21-21
OHM 120 mg QD 5-7
OHM 120 mg QD 7-21
OHM 20 mg QD 21-21
OHM 40 mg BID 21-21
OHM 40 mg QD 21-21
OHM 80 mg QD 21-21
OHM/DLBCL 80 mg QD 14-21
MK-8628
Up to 40 days after last dose of study therapy (Up to 28 months)
Number of Participants Who Discontinued Study Therapy Due to AEs
All participants who discontinued study therapy due to an AE at any time during treatment.
From time of first dose of study therapy until the end of treatment (up to 26 months)
Number of Participants Whose Best Response Was Partial Response (PR) or Complete Response (CR)
Best response was determined from the start of treatment until disease progression, recurrence, or completion of 26 months of treatment. Partial and complete response was assessed by bone marrow aspiration (AL participants); or computed tomography scan, magnetic resonance imaging, positron emission tomography, or X-ray (OHM participants) using standard criteria. Acute leukemia participants were assessed based on the recommendations from the European LeukemiaNet Döhner 2010); lymphoma participants according to Cheson 2007; and MM participants according to Durie 2006.
From time of first dose of study therapy until the end of treatment (up to 26 months)
Maximum Concentration (Cmax) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24 hours (h) + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Cmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Time to Maximum Concentration (Tmax) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Tmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Apparent Terminal Half-Life (t1/2) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for t1/2 were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Area Under the Concentration Time Curve of MK-8628/OTX015 From Time 0 to Infinity (AUC 0-inf)
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for AUC 0-first were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Apparent Total Body Clearance (CL/F) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for CL/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Volume of Distribution at Steady State (Vz/F) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Vz/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
Derived
Amorim S, Stathis A, Gleeson M, Iyengar S, Magarotto V, Leleu X, Morschhauser F, Karlin L, Broussais F, Rezai K, Herait P, Kahatt C, Lokiec F, Salles G, Facon T, Palumbo A, Cunningham D, Zucca E, Thieblemont C. Bromodomain inhibitor OTX015 in patients with lymphoma or multiple myeloma: a dose-escalation, open-label, pharmacokinetic, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e196-204. doi: 10.1016/S2352-3026(16)00021-1. Epub 2016 Mar 18.
Berthon C, Raffoux E, Thomas X, Vey N, Gomez-Roca C, Yee K, Taussig DC, Rezai K, Roumier C, Herait P, Kahatt C, Quesnel B, Michallet M, Recher C, Lokiec F, Preudhomme C, Dombret H. Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. Lancet Haematol. 2016 Apr;3(4):e186-95. doi: 10.1016/S2352-3026(15)00247-1. Epub 2016 Mar 18.
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG002
AL 40 mg QD 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG003
AL 20 mg BID 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
FG004
AL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG005
AL 40 mg BID 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 14 of a 21-day cycle.
FG006
AL 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG007
AL 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG008
AL 160 mg QD 14-21
Participants received 160 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG009
AML de Novo 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG010
AML/MDS 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG011
OHM 10 mg QD 21-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG012
OHM 20 mg QD 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG013
OHM 40 mg QD 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG014
OHM 80 mg QD 21-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG015
OHM 40 mg BID 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
FG016
OHM 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
FG017
OHM 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG018
OHM 120 mg QD 5-7
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 5 of a 7-day cycle.
FG019
OHM 120 mg QD 7-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 7 of a 21-day cycle.
FG020
OHM/DLBCL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
FG0003 subjectsNumber treated
FG0013 subjectsNumber treated
FG0024 subjectsNumber treated
FG0033 subjectsNumber treated
FG0044 subjectsNumber treated
FG0058 subjectsNumber treated
FG0067 subjectsNumber treated
FG0076 subjectsNumber treated
FG0086 subjectsNumber treated
FG00918 subjectsNumber treated
FG01016 subjectsNumber treated
FG0115 subjectsNumber treated
FG0123 subjectsNumber treated
FG0134 subjectsNumber treated
FG0147 subjectsNumber treated
FG0156 subjectsNumber treated
FG0167 subjectsNumber treated
FG0173 subjectsNumber treated
FG0185 subjectsNumber treated
FG0195 subjectsNumber treated
FG02015 subjectsNumber treated
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
FG0130 subjects
FG0140 subjects
FG0150 subjects
FG0160 subjects
FG0170 subjects
FG0180 subjects
FG0190 subjects
FG0200 subjects
NOT COMPLETED
FG0003 subjects
FG0013 subjects
FG0024 subjects
FG0033 subjects
FG0044 subjects
FG0058 subjects
FG0067 subjects
FG0076 subjects
FG0086 subjects
FG00918 subjects
FG01016 subjects
FG0115 subjects
FG0123 subjects
FG0134 subjects
FG0147 subjects
FG0156 subjects
FG0167 subjects
FG0173 subjects
FG0185 subjects
FG0195 subjects
FG02015 subjects
Type
Comment
Reasons
Disease progression
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG0032 subjects
FG0043 subjects
FG0053 subjects
FG0063 subjects
FG0073 subjects
FG0083 subjects
FG00911 subjects
FG01010 subjects
FG0115 subjects
FG0123 subjects
FG0133 subjects
FG0146 subjects
FG0156 subjects
FG0165 subjects
FG0172 subjects
FG0183 subjects
FG0195 subjects
FG02015 subjects
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Adverse event-related
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse event-unrelated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal of consent
FG0000 subjects
FG0010 subjects
FG0021 subjects
FG0030 subjects
FG004
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Stopped to receive bone marrow graft
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Disease progression and adverse event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 14 of a 21-day cycle.
BG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG002
AL 40 mg QD 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG003
AL 20 mg BID 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
BG004
AL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG005
AL 40 mg BID 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 14 of a 21-day cycle.
BG006
AL 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG007
AL 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG008
AL 160 mg QD 14-21
Participants received 160 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG009
AML de Novo 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG010
AML/MDS 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG011
OHM 10 mg QD 21-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG012
OHM 20 mg QD 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG013
OHM 40 mg QD 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG014
OHM 80 mg QD 21-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG015
OHM 40 mg BID 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
BG016
OHM 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
BG017
OHM 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG018
OHM 120 mg QD 5-7
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 5 of a 7-day cycle.
BG019
OHM 120 mg QD 7-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 7 of a 21-day cycle.
BG020
OHM/DLBCL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
BG021
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0013
BG0024
BG0033
BG0044
BG0058
BG0067
BG0076
BG0086
BG00918
BG01016
BG0115
BG0123
BG0134
BG0147
BG0156
BG0167
BG0173
BG0185
BG0195
BG02015
BG021138
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
ParticipantsBG0003
ParticipantsBG0013
ParticipantsBG0024
ParticipantsBG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0003
ParticipantsBG0013
ParticipantsBG002
Race and Ethnicity Not Collected
Race and Ethnicity were not collected from any participant.
Count of Participants
Participants
Title
Denominators
Categories
ParticipantsBG0000
ParticipantsBG0010
ParticipantsBG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
A DLT was graded using the National Cancer Institute-Common Toxicity Criteria for Adverse Events (NCI-CTCAE) version 4.02 and defined as any of the following: grade 3 or 4 non-hematologic adverse events unless they were not optimally treated with supportive care; grade 3 or 4 asymptomatic laboratory abnormal values lasting >7 days; prolonged grade 2 toxicity (lasting more than 2 weeks) leading to treatment interruption and/or dose reduction; pancytopenia with a hypocellular bone marrow and no marrow blasts lasting ≥6 weeks (AL participants); grade 3 neutropenia with fever or infection (OHM participants); grade 3 thrombocytopenia with bleeding (OHM participants); or grade 4 neutropenia or thrombocytopenia, regardless of symptoms and lasting ≥3 days (OHM participants).
All participants who received at least 85% of the intended dose of study therapy during the first cycle (i.e. >12 days at full dose for AL and >18 days at full dose for other hematological malignancies) or discontinued from the study due to a DLT attributable to study therapy.
Posted
Count of Participants
Participants
Cycle 1 (Up to 21 days)
ID
Title
Description
OG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 14 of a 21-day cycle.
OG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG002
AL 40 mg QD 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG003
AL 20 mg BID 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
OG004
AL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG005
AL 40 mg BID 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 14 of a 21-day cycle.
OG006
AL 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG007
AL 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
Units
Counts
Participants
OG0003
OG0013
OG0024
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Secondary
Number of Participants Who Experienced at Least One Adverse Event (AE)
AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have to have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product/protocol specified procedure, whether or not considered related to the medicinal product/protocol specified procedure. Any worsening of a preexisting condition temporally associated with the use of the product was also an AE. AEs were collected during the entire time frame of treatment plus up to 40 days of follow-up.
All participants who received at least one dose of study therapy.
Posted
Count of Participants
Participants
Up to 40 days after last dose of study therapy (Up to 28 months)
ID
Title
Description
OG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG002
AL 40 mg QD 14-21
Secondary
Number of Participants Who Discontinued Study Therapy Due to AEs
All participants who discontinued study therapy due to an AE at any time during treatment.
All participants who received at least one dose of study therapy.
Posted
Count of Participants
Participants
From time of first dose of study therapy until the end of treatment (up to 26 months)
ID
Title
Description
OG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG002
AL 40 mg QD 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG003
AL 20 mg BID 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
Secondary
Number of Participants Whose Best Response Was Partial Response (PR) or Complete Response (CR)
Best response was determined from the start of treatment until disease progression, recurrence, or completion of 26 months of treatment. Partial and complete response was assessed by bone marrow aspiration (AL participants); or computed tomography scan, magnetic resonance imaging, positron emission tomography, or X-ray (OHM participants) using standard criteria. Acute leukemia participants were assessed based on the recommendations from the European LeukemiaNet Döhner 2010); lymphoma participants according to Cheson 2007; and MM participants according to Durie 2006.
All participants who received one dose of study therapy and had at least one available tumor assessment by the end of Cycle 2 or later or with earlier evidence of response or progression.
Posted
Number
Participants
From time of first dose of study therapy until the end of treatment (up to 26 months)
ID
Title
Description
OG000
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
OG002
AL 40 mg QD 14-21
Secondary
Maximum Concentration (Cmax) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24 hours (h) + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Cmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
ug/L
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
Secondary
Time to Maximum Concentration (Tmax) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Tmax were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
Hours
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
Secondary
Apparent Terminal Half-Life (t1/2) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for t1/2 were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
Hours
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD in a fasted state.
Secondary
Area Under the Concentration Time Curve of MK-8628/OTX015 From Time 0 to Infinity (AUC 0-inf)
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for AUC 0-first were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
hr*ng/mL
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
Secondary
Apparent Total Body Clearance (CL/F) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for CL/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
L/hour
cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
Secondary
Volume of Distribution at Steady State (Vz/F) of MK-8628/OTX015
Data were collected in Cycle 1 according to dosing regimen and enrollment position at the following sampling schedules: 1) Complete QD for the first 3 participants per dose level: Pre-infusion and 1, 4, 8, 12, and 24h + 1 sampling at either 10h or 16h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 2) Limited QD for participants 4 and higher: Pre-infusion and 1, 4, 6, and 8h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level; 3) BID: Pre-infusion and at 20 minutes and 1, 2.25, 3.25. 9, 12, and 24h post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion per dose level.
Blood samples for Vz/F were measured using liquid chromatography-tandem mass spectrometry and analyzed using a nonlinear mixed-effects modelling software program Monolix version 4.3.2. Results for each dose level and method of administration included participants from both AL and OHM cohorts and different regimen frequencies.
All participants that received at least 1 dose of study therapy and had evaluable data for endpoint. Results were pooled by dose taken and not by disease or regimen.
Posted
Mean
Standard Deviation
Liters
Cycle 1: Pre-infusion and 20 minutes; 1, 2.25, 3.25, 4, 6, 8, 9, 12, and 24 hours plus one sampling at either 10 hour or 16 hour post-infusion on Days 1 and 2 and on Days 8, 15, and 22 pre-infusion dependent on dose regimen and enrollment position
ID
Title
Description
OG000
10 mg QD Dose Escalation Cohort
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state.
Time Frame
Adverse events were monitored up to 40 days after last dose of study therapy (Up to 28 months).
Description
The safety population consisted of all participants who received at least one dose of study therapy.
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
AL 10 mg QD 14-21
Participants received 10 mg MK-8628/OTX015 administered orally (PO), once daily (QD), in a fasted state on Days 1 to 14 of a 21-day cycle.
3
3
1
3
3
3
EG001
AL 20 mg QD 14-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
3
3
2
3
3
3
EG002
AL 40 mg QD 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
4
4
3
4
4
4
EG003
AL 20 mg BID 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
3
3
1
3
3
3
EG004
AL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
4
4
3
4
4
4
EG005
AL 40 mg BID 14-21
Participants received 40 mg MK-8628/OTX015 administered PO, twice a day (BID), with the first daily dose in a fasted state, on Days 1 to 14 of a 21-day cycle.
7
8
7
8
8
8
EG006
AL 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
7
7
6
7
7
7
EG007
AL 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
6
6
5
6
6
6
EG008
AL 160 mg QD 14-21
Participants received 160 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
6
6
4
6
6
6
EG009
AML de Novo 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
15
18
14
18
18
18
EG010
AML/MDS 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
15
16
14
16
16
16
EG011
OHM 10 mg QD 21-21
Participants received 10 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
3
5
3
5
5
5
EG012
OHM 20 mg QD 21-21
Participants received 20 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
2
3
1
3
3
3
EG013
OHM 40 mg QD 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
2
4
0
4
4
4
EG014
OHM 40 mg BID 21-21
Participants received 40 mg MK-8628/OTX015 administered PO, BID, with the first daily dose in a fasted state, on Days 1 to 21 of a 21-day cycle.
4
6
5
6
6
6
EG015
OHM 120 mg QD 21-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
5
7
6
7
7
7
EG016
OHM 120 mg QD 14-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
1
3
2
3
3
3
EG017
OHM 120 mg QD 5-7
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 5 of a 7-day cycle.
2
5
2
5
5
5
EG018
OHM 120 mg QD 7-21
Participants received 120 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 7 of a 21-day cycle.
5
5
2
5
5
5
EG019
OHM/DLBCL 80 mg QD 14-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 14 of a 21-day cycle.
9
15
5
15
15
15
EG020
OHM 80 mg QD 21-21
Participants received 80 mg MK-8628/OTX015 administered PO, QD, in a fasted state on Days 1 to 21 of a 21-day cycle.
4
7
4
7
7
7
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG0030 affected3 at risk
EG0040 affected4 at risk
EG0050 affected8 at risk
EG0060 affected7 at risk
EG0070 affected6 at risk
EG0080 affected6 at risk
EG0090 affected18 at risk
EG0102 affected16 at risk
EG0110 affected5 at risk
EG0120 affected3 at risk
EG0130 affected4 at risk
EG0141 affected6 at risk
EG0150 affected7 at risk
EG0160 affected3 at risk
EG0170 affected5 at risk
EG0180 affected5 at risk
EG0190 affected15 at risk
EG0201 affected7 at risk
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Febrile bone marrow aplasia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0023 affected4 at risk
EG003
Haemorrhagic disorder
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Atrial flutter
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cardiac failure
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pericardial effusion
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sinus bradycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Anorectal disorder
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Faecal incontinence
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastric haemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastric ulcer haemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Intestinal obstruction
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Disease progression
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
General physical health deterioration
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Puncture site haemorrhage
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Aspergillosis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bronchopulmonary aspergillosis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Cerebral aspergillosis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Device related infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Enterobacter infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eye infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastrointestinal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Infectious peritonitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Lung infection pseudomonal
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neutropenic sepsis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pseudomonas infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Septic shock
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Viral skin infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood calcium increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Enterococcus test positive
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Factor VII deficiency
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperbilirubinaemia
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Transaminases increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tumour lysis syndrome
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Malignant melanoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Depressed level of consciousness
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemorrhage intracranial
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Syncope
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oliguria
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pelvic pain
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bronchial haemorrhage
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Chest pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pneumomediastinum
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pulmonary haemorrhage
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Air embolism
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypotension
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombosis
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anaemia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 affected3 at risk
EG0012 affected3 at risk
EG0023 affected4 at risk
EG0031 affected3 at risk
EG0044 affected4 at risk
EG0057 affected8 at risk
EG0065 affected7 at risk
EG0075 affected6 at risk
EG0083 affected6 at risk
EG0099 affected18 at risk
EG0107 affected16 at risk
EG0111 affected5 at risk
EG0120 affected3 at risk
EG0131 affected4 at risk
EG0143 affected6 at risk
EG0151 affected7 at risk
EG0161 affected3 at risk
EG0173 affected5 at risk
EG0180 affected5 at risk
EG0191 affected15 at risk
EG0204 affected7 at risk
Disseminated intravascular coagulation
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Febrile neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Haemorrhagic disorder
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Leukocytosis
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Lymph node pain
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Splenomegaly
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombocytopenia
Blood and lymphatic system disorders
MedDRA 20.0
Non-systematic Assessment
EG0002 affected3 at risk
EG0012 affected3 at risk
EG0022 affected4 at risk
EG003
Arrhythmia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cardiac arrest
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Conduction disorder
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Palpitations
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Supraventricular extrasystoles
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tachycardia
Cardiac disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Factor V deficiency
Congenital, familial and genetic disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Deafness
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Ear pain
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Conjunctival haemorrhage
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Conjunctivitis
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dry eye
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Exophthalmos
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eye disorder
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eye haemorrhage
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eye pain
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Periorbital oedema
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Photophobia
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Ulcerative keratitis
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vision blurred
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Visual acuity reduced
Eye disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal discomfort
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal distension
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Anorectal discomfort
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Breath odour
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cheilitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Constipation
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dry mouth
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Duodenogastric reflux
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dysphagia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Faecal incontinence
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Faeces discoloured
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Flatulence
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastrointestinal pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastrooesophageal reflux disease
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Gingival bleeding
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gingival disorder
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gingival hypertrophy
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gingival pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematochezia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemorrhoids
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Mouth haemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Odynophagia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oesophagitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oral pain
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Proctalgia
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rectal haemorrhage
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tongue coated
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Asthenia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0013 affected3 at risk
EG0023 affected4 at risk
EG003
Cancer pain
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Catheter site related reaction
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Chills
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Facial pain
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Feeling cold
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
General physical health deterioration
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Influenza like illness
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Irritability
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Localised Oedema
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Malaise
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oedema
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oedema peripheral
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pain
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Puncture site haemorrhage
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Puncture site pain
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Puncture site reaction
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pyrexia
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sense of oppression
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Swelling
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Weight decreased
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0022 affected4 at risk
EG003
Weight increased
General disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cholestasis
Hepatobiliary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cytolytic hepatitis
Hepatobiliary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Jaundice
Hepatobiliary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Seasonal allergy
Immune system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Anal abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Aspergillosis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bacterial infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Bronchopneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bronchopulmonary aspergillosis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Candidiasis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cellulitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Clostridial infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Clostridium difficile colitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Cystitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Device related infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eye infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Folliculitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fungal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gastroenteritis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Gingival infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Herpes virus infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Human herpesvirus 6 infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Infection reactivation
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Influenza
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Localized infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lower respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lyme disease
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lymphangitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oral candidiasis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Oral fungal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Paronychia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Periodontal infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Pneumonia
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Prostate infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Prostatitis escherichia coli
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pyelonephritis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Respiratory syncytial virus infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rhinitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rhinotracheitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sepsis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sinusitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tinea Cruris
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tooth abscess
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tooth infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tracheitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Viral skin infection
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vulvitis
Infections and infestations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Contusion
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Excoriation
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Eyelid injury
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Limb injury
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Post procedural haemorrhage
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin injury
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thermal burn
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Transfusion related complication
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Wound
Injury, poisoning and procedural complications
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Aspergillus test positive
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bilirubin conjugated increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood creatinine increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Blood magnesium decreased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
C-reactive protein increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Electrocardiogram QT prolonged
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Factor VII deficiency
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hyperbilirubinaemia
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
International normalised ratio
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
International normalised ratio decreased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
International normalised ratio increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Prothrombin time prolonged
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Prothrombin time shortened
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Transaminases increased
Investigations
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Acidosis
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Decreased appetite
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0021 affected4 at risk
EG003
Dehydration
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fluid overload
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Fluid retention
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypercalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperglycaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperkalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperuricaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypocalcaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypokalaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hypomagnesaemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyponatraemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypophosphataemia
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Obesity
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Type 2 diabetes mellitus
Metabolism and nutrition disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Back disorder
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bone disorder
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Flank pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Muscle contracture
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Muscle spasms
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Muscular weakness
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Musculoskeletal chest pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rhabdomyolysis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tendonitis
Musculoskeletal and connective tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Leukoerythroblastosis
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tumour haemorrhage
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Anaesthesia
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Convulsion
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dizziness
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Facial nerve disorder
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Headache
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Intracranial aneurysm
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Migraine
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neuralgia
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Neuropathy peripheral
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Peripheral motor neuropathy
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Peripheral sensory neuropathy
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Presyncope
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sciatica
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Sinus headache
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Somnolence
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Tremor
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Viith nerve paralysis
Nervous system disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Agitation
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Depression
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hallucination, visual
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dysuria
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematuria
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Micturition urgency
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nocturia
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pollakiuria
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Renal failure
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary hesitation
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary incontinence
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary retention
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary tract disorder
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urinary tract pain
Renal and urinary disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Breast pain
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Erectile dysfunction
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nipple disorder
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Prostatitis
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vaginal haemorrhage
Reproductive system and breast disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Chest pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0022 affected4 at risk
EG003
Dysphonia
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected4 at risk
EG003
Dyspnoea exertional
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haemoptysis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Interstitial lung disease
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Laryngeal haemorrhage
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung consolidation
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Lung disorder
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected4 at risk
EG003
Nasal congestion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Nasal inflammation
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pleural effusion
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Productive cough
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pulmonary fibrosis
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pulmonary haemorrhage
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rhinorrhoea
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Wheezing
Respiratory, thoracic and mediastinal disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Alopecia
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Decubitus ulcer
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermal cyst
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermatitis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermatitis acneiform
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermatitis allergic
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dermatitis exfoliative
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Dry skin
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eccymosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Eczema
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Erythrosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Intertrigo
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Night sweats
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Petechiae
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pruritus
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Purpura
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Rash pruritic
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Scab
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin disorder
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin exfoliation
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Skin lesion
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Flushing
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Haematoma
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hot flush
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypertension
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Hypotension
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Pallor
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Phlebitis
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombophlebitis superficial
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Thrombosis
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Vasculitis
Vascular disorders
MedDRA 20.0
Non-systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected4 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
The Sponsor has the opportunity to review all proposed publications regarding this trial 60 days prior to submission for publication. In addition, if requested, the investigator will withhold publication an additional 90 days to allow for filing a patent application or taking such other measures to establish and preserve its proprietary rights. Publication of the results of the study shall be made only as part of a publication of the results obtained by all sites performing the protocol.
Point of Contact
Title
Organization
Phone
Extension
Email
Senior Vice President, Global Clinical Development