The classic website will no longer be available as of June 25, 2024. Please use the modernized ClinicalTrials.gov.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Assess the Safety and Efficacy of Two Combinations of Isocitrate Dehydrogenase (IDH) Mutant Targeted Therapies Plus Azacitidine in Participants With Newly Diagnosed Acute Myeloid Leukemia (AML) Harboring IDH Mutations Who Are Not Candidates to Receive Intensive Induction Chemotherapy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02677922
Recruitment Status : Active, not recruiting
First Posted : February 9, 2016
Results First Posted : November 22, 2022
Last Update Posted : January 25, 2024
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Leukemia, Myeloid, Acute
Interventions Drug: AG-120
Drug: Azacitidine
Drug: AG-221
Enrollment 130
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Period Title: Pre-Treatment Period
Started 3 3 7 16 68 33
Completed 3 3 7 16 68 32
Not Completed 0 0 0 0 0 1
Reason Not Completed
Withdrawal by Subject             0             0             0             0             0             1
Period Title: Treatment Period
Started 3 3 7 16 68 32
Completed [1] 1 1 4 3 21 1
Not Completed 2 2 3 13 47 31
Reason Not Completed
Adverse Event             0             0             1             3             5             2
Progressive Disease             1             1             0             0             8             7
Lack of Efficacy             0             0             0             1             1             6
Withdrawal by Subject             0             0             1             3             5             5
Transition to Commercially Available Treatment             0             1             1             1             1             2
Disease Relapse             0             0             0             3             6             1
Allogeneic HSCT             1             0             0             1             4             1
Other Reasons             0             0             0             1             3             5
Death             0             0             0             0             12             1
Non-compliance with Study Drug             0             0             0             0             1             0
Physician Decision             0             0             0             0             0             1
Symptomatic Deterioration             0             0             0             0             1             0
[1]
Ongoing
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy Total
Hide Arm/Group Description Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle Total of all reporting groups
Overall Number of Baseline Participants 3 3 7 16 68 33 130
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 16 participants 68 participants 33 participants 130 participants
< 65
0
   0.0%
1
  33.3%
0
   0.0%
3
  18.8%
7
  10.3%
1
   3.0%
12
   9.2%
>= 65-< 75
1
  33.3%
2
  66.7%
2
  28.6%
6
  37.5%
22
  32.4%
14
  42.4%
47
  36.2%
>= 75
2
  66.7%
0
   0.0%
5
  71.4%
7
  43.8%
39
  57.4%
18
  54.5%
71
  54.6%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 16 participants 68 participants 33 participants 130 participants
Female
2
  66.7%
2
  66.7%
3
  42.9%
9
  56.3%
36
  52.9%
11
  33.3%
63
  48.5%
Male
1
  33.3%
1
  33.3%
4
  57.1%
7
  43.8%
32
  47.1%
22
  66.7%
67
  51.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 16 participants 68 participants 33 participants 130 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
1
  14.3%
0
   0.0%
1
   1.5%
1
   3.0%
3
   2.3%
Not Hispanic or Latino
3
 100.0%
3
 100.0%
6
  85.7%
14
  87.5%
51
  75.0%
26
  78.8%
103
  79.2%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
2
  12.5%
16
  23.5%
6
  18.2%
24
  18.5%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 3 participants 3 participants 7 participants 16 participants 68 participants 33 participants 130 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.3%
1
   1.5%
1
   3.0%
3
   2.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
1
  33.3%
1
  33.3%
0
   0.0%
0
   0.0%
5
   7.4%
1
   3.0%
8
   6.2%
White
2
  66.7%
2
  66.7%
7
 100.0%
13
  81.3%
49
  72.1%
24
  72.7%
97
  74.6%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
2
  12.5%
13
  19.1%
7
  21.2%
22
  16.9%
1.Primary Outcome
Title The Number of Participants Experiencing Dose-limiting Toxicities (DLTs): Phase 1B (Dose Finding Stage)
Hide Description Dose-limiting toxicities (DLTs) are defined as an event that constitute a change from baseline irrespective of outcome and determined by the investigator to be related to treatment. The DLT-evaluable participants were defined as participants who took at least 1 dose of study drug in the Phase 1b Dose-Finding Stage and either had a DLT during Cycle 1 (regardless of amount of study drug exposure), or had no DLT and completed at least 75% of AG-120 or AG-221 doses (21 out of 28 days) and a minimum of 5 doses of AZA, at least 50% of the planned combination doses for AG-120 or AG-221 and AZA administered together (in the same day for 4 out of 7 days) in the first 28 days from C1D1, and were also considered by the Clinical Study Team to have sufficient safety data available to conclude that a DLT did not occur during Cycle 1.
Time Frame From first dose to 28 days after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
All DLT evaluable participants in the Phase 1b (Dose-finding Stage)
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 3 3 7
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
2.Primary Outcome
Title The Number of Participants Experiencing Adverse Events: Phase 1B (Dose Finding and Expansion Stage)
Hide Description The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or constitutes an important medical event. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). Treatment-emergent adverse events (TEAE) was defined as events that began on or after the start of study drug through 28 days after the last study treatment. The severity/intensity of AEs were graded based upon the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
Time Frame From first dose to 28 days after last dose (up to approximately 13 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Phase 1B (Dose Finding and Expansion Stage)
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 3 3 7 16
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at Least One TEAE
3
 100.0%
3
 100.0%
7
 100.0%
16
 100.0%
Participants with at Least One TEAE Related to Study Drug(s)
3
 100.0%
3
 100.0%
7
 100.0%
16
 100.0%
Participants with at Least One Grade 3-4 TEAE
3
 100.0%
3
 100.0%
7
 100.0%
15
  93.8%
Participants with at least One Grade 3-4 TEAE Related to Study Drug(s)
2
  66.7%
2
  66.7%
4
  57.1%
10
  62.5%
Participants with at Least One Grade 5 TEAE
0
   0.0%
1
  33.3%
1
  14.3%
2
  12.5%
Participants with at Least One Grade 5 TEAE Related to Study Drug(s)
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Participants with at Least One Serious TEAE
3
 100.0%
2
  66.7%
4
  57.1%
11
  68.8%
Participants with at Least One Serious TEAE Related to Study Drug(s)
0
   0.0%
1
  33.3%
1
  14.3%
5
  31.3%
Participants with at Least One TEAE Leading to Discontinuation of Study Drug(s)
1
  33.3%
0
   0.0%
1
  14.3%
4
  25.0%
Participants with at Least One Study Drug Related TEAE Leading to Discontinuation of Study Drug
0
   0.0%
0
   0.0%
0
   0.0%
1
   6.3%
Participants with at Least One TEAE Leading to Dose Reduction of Study Drug(s)
1
  33.3%
1
  33.3%
2
  28.6%
5
  31.3%
Participants with at Least One TEAE Leading to Dose Interruption of Study Drug(s)
3
 100.0%
3
 100.0%
2
  28.6%
11
  68.8%
Participants with at Least One Study Drug(s) Related TEAE Leading to Study Drug Dose Reduction
0
   0.0%
1
  33.3%
1
  14.3%
5
  31.3%
Participants with at Least One Study Drug(s) Related TEAE Leading to Study Drug Dose Interruption
1
  33.3%
2
  66.7%
2
  28.6%
8
  50.0%
3.Primary Outcome
Title Overall Response Rate: Phase 2 (Randomized Stage)
Hide Description The percent of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria as assessed by investigator. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
Time Frame From first dose up to approximately 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
73.5
(61.4 to 83.5)
36.4
(20.4 to 54.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0003
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 4.86
Confidence Interval (2-Sided) 95%
1.99 to 11.85
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Overall Response Rate: Phase 1B (Dose Finding and Expansion Stage)
Hide Description Percent of participants with MLFS + CR + CRi + CRp + PR according to modified International Working Group Acute Myeloid Leukemia (IWG AML) response criteria as assessed by investigator. Complete response (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. Partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
Time Frame From first dose up to approximately 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Phase 1B (Dose Finding and Expansion Stage)
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 3 3 7 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
66.7
(9.4 to 99.2)
66.7
(9.4 to 99.2)
100
(59.0 to 100)
68.8
(41.3 to 89.0)
5.Secondary Outcome
Title Sponsor Derived CR and CRh: Phase 1B (Dose Finding and Expansion Stage)
Hide Description The percent of participants with morphologic complete remission (CR) and morphologic complete remission with partial hematologic recovery (CRh) based on laboratory data. CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. CRh is defined as less than 5% blasts in a BM aspirate sample with marrow spicules plus ANC > 500 x 109/L (1,000/μL) & Platelet count > 50 x 109/L (100,000/μL). CRh is defined as Response of bone marrow blast <5% with absolute neutrophil count (ANC) > 0.5 × 10^9/L and platelet > 50 × 10^9/L.
Time Frame From first dose up to approximately 13 months
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Phase 1B (Dose Finding and Expansion Stage)
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 3 3 7 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
66.7
(9.4 to 99.2)
66.7
(9.4 to 99.2)
71.4
(29.0 to 96.3)
62.5
(35.4 to 84.8)
6.Secondary Outcome
Title Event-free Survival (EFS): Phase 2 (Randomized Stage)
Hide Description Event-Free Survival is the time from date of randomization to the date of documented morphologic relapse, progression, or death from any cause, whichever occurs first. Morphologic Relapse is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. Progression is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.
Time Frame From randomization to the date of documented relapse, progression, or death due to any cause, whichever occurs first (up to approximately 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Median (95% Confidence Interval)
Unit of Measure: Months
15.9 [1] 
(13.0 to NA)
11.9
(8.2 to 15.5)
[1]
Insufficient number of participants with events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1083
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.30 to 1.13
Estimation Comments [Not Specified]
7.Secondary Outcome
Title The Number of Participants Experiencing Adverse Events: Phase 2 (Randomized Stage)
Hide Description The number of participants experiencing different types of adverse events (AE). An AE is any noxious, unintended, or untoward medical occurrence that may appear or worsen in a participant during the course of a study. A Serious Adverse Event (SAE) is any AE occurring at any dose that: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or constitutes an important medical event. Adverse events were analyzed in terms of treatment-emergent AEs (TEAEs). Treatment-emergent adverse events (TEAE) was defined as events that began on or after the start of study drug through 28 days after the last study treatment. The severity/intensity of AEs were graded based upon the Common Terminology Criteria for Adverse Events (CTCAE, Version 4.03) where Grade 3 = Severe, Grade 4 = Life-threatening, and Grade 5 = Death.
Time Frame From first dose to 28 days after last dose (up to approximately 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All treated participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 32
Measure Type: Count of Participants
Unit of Measure: Participants
Participants with at Least One TEAE
68
 100.0%
32
 100.0%
Participants with at Least One TEAE Related to Study Drug(s)
62
  91.2%
26
  81.3%
Participants with at Least One Grade 3-4 TEAE
68
 100.0%
31
  96.9%
Participants with at least One Grade 3-4 TEAE Related to Study Drug(s)
50
  73.5%
20
  62.5%
Participants with at Least One Grade 5 TEAE
15
  22.1%
2
   6.3%
Participants with at Least One Grade 5 TEAE Related to Study Drug(s)
0
   0.0%
0
   0.0%
Participants with at Least One Serious TEAE
64
  94.1%
25
  78.1%
Participants with at Least One Serious TEAE Related to Study Drug(s)
29
  42.6%
14
  43.8%
8.Secondary Outcome
Title Complete Remission Rate: Phase 2 (Randomized Stage)
Hide Description The percent of participants with morphologic complete remission (CR) according to modified International Working Group Acute Myeloid Leukemia Response Criteria (IWG AML). CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease; plus the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment.
Time Frame From first dose up to approximately 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
54.4
(41.9 to 66.5)
12.1
(3.4 to 28.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 8.65
Confidence Interval (2-Sided) 95%
2.74 to 27.31
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Hematologic Improvement (HI) Rate: Phase 2 (Randomized Stage)
Hide Description The percent of participants with hematologic improvement neutrophil response (HI-N) + hematologic improvement platelet response (HI-P) + hematologic improvement erythroid response (HI-E) according to the International Working Group for Myelodysplastic Syndromes for Hematologic Improvement (IWG MDS HI) criteria. HI-E is defined as a hemoglobin increase by ≥ 1.5 g/dL and a relevant reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 week compared with the pretreatment transfusion number in the previous 8 week. HI-P is defined as an absolute increase of ≥ 30 X 10^9/L for participants starting with > 20 X and an increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-N is defined as At least 100% increase and an absolute increase > 0.5 X 10^9/L.
Time Frame From first dose up to approximately 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
70.6
(58.3 to 81.0)
57.6
(39.2 to 74.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1943
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.77
Confidence Interval (2-Sided) 95%
0.74 to 4.20
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Duration of Response: Phase 2 (Randomized Stage)
Hide Description The time from first documented CR/CRi/CRp/PR/MLFS to documented morphologic relapse, progression, or death due to any cause, whichever occurred first. CR and MLFS are defined as <5% blasts in a BM aspirate sample with marrow spicules + a count of ≥200 nucleated cells with no blasts with Auer rods + no extramedullary disease. CR must also include: ANC ≥ 1,000/μL, Platelet count ≥100,000/μL, + independent of red cell transfusions for ≥1 week before assessment. CRi is all criteria of CR except ANC. CRp is all criteria of CR except platelet count. PR is defined as all hematologic criteria of CR with >50% decrease in BM blasts to 5%-25%. Relapse is defined as reappearance of ≥ 5% blasts in the BM not attributable to other cause or development of extramedullary disease. Progression is defined as > 50% increase of BM blast count from baseline to ≥ 20% or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10,000/μL or development of new extramedullary disease.
Time Frame From first dose up to approximately 26 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage) who achieved CR/CRi/CRp/PR/MLFS
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 50 12
Median (95% Confidence Interval)
Unit of Measure: Months
24.1 [1] 
(10.0 to NA)
9.9
(5.5 to 13.6)
[1]
Insufficient number of participants with events
11.Secondary Outcome
Title Time to Response: Phase 2 (Randomized Stage)
Hide Description Time from first dose of study drug to first documented MLFS/CR/CRi/CRp/PR according to modified IWG AML response criteria. Complete remission (CR) and morphologic leukemia-free state (MLFS) are defined as <5% blasts in a BM aspirate sample with marrow spicules and a count of ≥200 nucleated cells. There should be no blasts with Auer rods and no extramedullary disease. CR must also include the following conditions: absolute neutrophil count (ANC) ≥1,000/μL, Platelet count ≥100,000/μL, and independent of red cell transfusions for ≥1 week before each response assessment. Complete remission with incomplete neutrophil recovery (CRi) is all criteria of CR except ANC. Complete remission with incomplete platelet recovery (CRp) is all criteria of CR except platelet count. partial remission (PR) is defined as all hematologic criteria of CR with a >50% decrease in the percentage of BM blasts to 5% to 25%. (<5% considered if Auer rods are present).
Time Frame From first dose to to first documented MLFS/CR/CRi/CRp/PR (up to approximately 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage) who achieved CR/CRi/CRp/PR/MLFS
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 50 12
Mean (Standard Deviation)
Unit of Measure: Months
3.05  (2.551) 3.42  (1.720)
12.Secondary Outcome
Title Overall Survival: Phase 2 (Randomized Stage)
Hide Description Overall survival (OS) is defined as time from randomization to death due to any cause.
Time Frame From randomization to date of death (up to approximately 26 months)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Median (95% Confidence Interval)
Unit of Measure: Months
22.0 [1] 
(14.6 to NA)
22.3 [1] 
(11.9 to NA)
[1]
Insufficient number of participants with events
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9720
Comments [Not Specified]
Method Log Rank
Comments Unstratified log-rank test
Method of Estimation Estimation Parameter Cox Proportional Hazard
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.52 to 1.87
Estimation Comments Cox proportional hazards regression model
13.Secondary Outcome
Title One Year Survival Rate: Phase 2 (Randomized Stage)
Hide Description The percent of participants alive at 1 year from randomization
Time Frame From randomization to 1 year after randomization
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 68 33
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
72.2
(59.6 to 81.5)
69.6
(49.6 to 82.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Phase 2 Randomized Stage: AG-221 (100mg) + AZA, Phase 2 Randomized Stage: AZA Monotherapy
Comments [Not Specified]
Type of Statistical Test Other
Comments Confidence interval of difference
Method of Estimation Estimation Parameter Difference
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-17.3 to 22.5
Estimation Comments The CI for the difference was derived using Greenwood's variance estimate.
14.Secondary Outcome
Title AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 1B (Expansion Stage)
Hide Description Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.
Time Frame Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-120 treated participants with available pharmacokinetic measurements in Phase 1B (Expansion Stage)
Arm/Group Title Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: (h*ng/mL)
CYCLE 1 DAY 1 31952.4465  (16008.00412)
CYCLE 2 DAY 1 44291.5504  (18806.17037)
15.Secondary Outcome
Title Cmax- Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)
Hide Description Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data
Time Frame Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-120 treated participants with available pharmacokinetic measurements in Phase 1B (Expansion Stage)
Arm/Group Title Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 15
Mean (Standard Deviation)
Unit of Measure: (ng/mL)
CYCLE 1 DAY 1 Number Analyzed 15 participants
6058.0  (2750.97)
CYCLE 2 DAY 1 Number Analyzed 14 participants
6340.7  (3191.00)
16.Secondary Outcome
Title Tmax- Time of Maximum Observed Plasma Concentration: Phase 1B (Expansion Stage)
Hide Description Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
Time Frame Pre-dose, 0.5, 2, 3, 4, 6, 8 hours post dose (± 10 minutes) on day 1 of cycle 1 and 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-120 treated participants with available pharmacokinetic measurements in Phase 1B (Expansion Stage)
Arm/Group Title Phase 1b Expansion Stage: AG-120 (500mg) + AZA
Hide Arm/Group Description:
Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 15
Median (Full Range)
Unit of Measure: (h)
CYCLE 1 DAY 1 Number Analyzed 15 participants
3.0000
(0.500 to 8.067)
CYCLE 2 DAY 1 Number Analyzed 14 participants
2.5000
(0.500 to 7.850)
17.Secondary Outcome
Title AUC (0-8)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)
Hide Description Area under the plasma concentration-time curve from time zero to 8 hours, calculated using the linear trapezoid rule.
Time Frame Pre-dose, 2, 3, 4, 6, and 8 hours post dose (± 10 minutes) on day 1 of cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-221 treated participants with available pharmacokinetic measurements in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: (h*ng/mL)
100302.8231  (61286.98611)
18.Secondary Outcome
Title AUC (0-24)- Area Under the Plasma Concentration-Time Curve: Phase 2 (Randomized Stage)
Hide Description AUC0-24: Area under the plasma concentration-time curve from time zero to 24 hours, calculated using the linear trapezoid rule.
Time Frame Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-221 treated participants with available pharmacokinetic measurements in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 13
Mean (Standard Deviation)
Unit of Measure: (h*ng/mL)
285864.2637  (190300.31922)
19.Secondary Outcome
Title Cmax- Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)
Hide Description Cmax: Maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
Time Frame Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-221 treated participants with available pharmacokinetic measurements in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 16
Mean (Standard Deviation)
Unit of Measure: (ng/mL)
15965.0  (9663.47)
20.Secondary Outcome
Title Tmax- Time of Maximum Observed Plasma Concentration: Phase 2 (Randomized Stage)
Hide Description Tmax: Time of maximum observed plasma concentration, obtained directly from the observed concentration versus time data.
Time Frame Pre-dose, 2, 3, 4, 6, 8, and 24 hours post dose (± 10 minutes) on day 1 of cycle 2
Hide Outcome Measure Data
Hide Analysis Population Description
All AG-221 treated participants with available pharmacokinetic measurements in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Overall Number of Participants Analyzed 16
Median (Full Range)
Unit of Measure: (h)
2.5333
(0.000 to 23.917)
21.Secondary Outcome
Title Change From Baseline in Health-related Quality-of-Life Domain Scores of the EORTC QLQ-C30: Phase 2 (Randomized Stage)
Hide Description The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) is composed of 30 items that address general physical symptoms, physical functioning, fatigue and malaise, and social and emotional functioning. Subscale scores are transformed to a 0 to 100 scale, with higher scores on functional scales indicating better function and higher scores on symptom scales indicating worse symptoms. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values. EORTC QLQ-C30 is assessed prior to dosing and prior to interaction with study personnel.
Time Frame Baseline and Day 1 Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline assessment in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 28 17
Mean (Standard Deviation)
Unit of Measure: Score on a scale
Global QoL 12.2  (27.36) 4.9  (27.33)
Physical functioning 1.9  (20.6) 6.7  (23.57)
Role functioning -0.6  (29.57) 1.0  (30.88)
Cognitive functioning -4.8  (26.00) 4.9  (25.53)
Emotional functioning 7.7  (24.42) 8.8  (18.51)
Social functioning -6.5  (29.52) 6.9  (34.89)
Fatigue -17.5  (33.05) -8.5  (31.06)
Nausea and vomiting -6.0  (29.47) 1.0  (16.11)
Pain -13.1  (33.13) -4.9  (30.48)
Dyspnea -27.4  (35.20) -9.8  (28.30)
Insomnia -6.0  (25.75) -13.7  (26.51)
Appetite loss -7.1  (42.90) -5.9  (35.81)
Constipation 6.0  (32.78) -9.8  (22.87)
Diarrhea -7.1  (31.89) -5.9  (29.43)
Financial difficulties 8.3  (19.51) -2.0  (34.30)
22.Secondary Outcome
Title Change From Baseline in Health Utility Indices of the EQ-5D-5L: Phase 2 (Randomized Stage)
Hide Description The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. These health states are converted to a single index value using the crosswalk method to the EQ-5D-3L value set from the United Kingdom (UK). The EQ-5D-3L health utility index based on the UK population weights range from -0.594 to 1.0 with higher scores indicating higher health utility. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
Time Frame Baseline and Day 1 Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline assessment in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 28 14
Mean (Standard Deviation)
Unit of Measure: Score on a scale
0.04  (0.216) 0.02  (0.211)
23.Secondary Outcome
Title Change From Baseline in Visual Analogue Scale (VAS) Scores of the EQ-5D-5L: Phase 2 (Randomized Stage)
Hide Description The European Quality of Life 5D-5L (EQ-5D-5L) instrument has a respondent's self-rated today's health scale which is recorded on a VAS with endpoints labeled "the best health you can imagine" and "the worst health you can imagine." The scale is numbered from 0 to 100 with 0 corresponding to the worst imaginable health state and 100 corresponding to the best imaginable health state. A high score represents a better level of QoL. Baseline results are obtained just prior to the start of study treatment on Day 1 of Cycle 1 and will serve as the baseline values.
Time Frame Baseline and Day 1 Cycle 5
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants with baseline and at least one post-baseline assessment in Phase 2 (Randomized Stage)
Arm/Group Title Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description:
Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle.
Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
Overall Number of Participants Analyzed 28 17
Mean (Standard Deviation)
Unit of Measure: Score on a scale
13.00  (26.166) 1.65  (27.897)
24.Secondary Outcome
Title Sponsor Derived CR: Phase 2 (Randomized Stage)
Hide Description The number of participants with Morphologic Complete Remission (CR) based on laboratory data. CR is defined as as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment.
Time Frame From first dose to end of study
Outcome Measure Data Not Reported
25.Secondary Outcome
Title Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)
Hide Description The number of participants with morphologic complete remission (CR) and morphologic complete remission with partial hematologic recovery (CRh) based on laboratory data. CR is defined as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. CRh is defined as Response of bone marrow blast <5% with absolute neutrophil count (ANC) > 0.5 × 10^9/L and platelet > 50 × 10^9/L.
Time Frame From first dose to end of study
Outcome Measure Data Not Reported
26.Secondary Outcome
Title Time to Sponsor Derived CR and CRh: Phase 2 (Randomized Phase)
Hide Description Time from first dose of study drug to first documented CR/CRh. Morphologic Complete Remission (CR) is defined as as less than 5% blasts in a BM aspirate sample with marrow spicules and with a count of at least 200 nucleated cells. There should be no blasts with Auer rods and absence of extramedullary disease. Plus, all the following conditions should be met: ANC ≥ 1 x 109/L (1,000/μL), platelet count ≥ 100 x 109/L (100,000/μL), independent of red cell transfusions for ≥ 1 week immediately before each response assessment. Morphologic complete remission with partial hematologic recovery (CRh) is defined as less than 5% blasts in a BM aspirate sample with marrow spicules plus ANC > 500 x 109/L (1,000/μL) & Platelet count > 50 x 109/L (100,000/μL).
Time Frame From first dose to end of study
Outcome Measure Data Not Reported
27.Secondary Outcome
Title Duration of Sponsor Derived CR/CRh: Phase 2 (Randomized Stage)
Hide Description Time from first documented CR/CRh to documented morphologic relapse, PD, or death due to any cause, whichever occurred first. Participants without morphologic relapse, PD, or death due to any cause were censored at the date of the last response assessment. Morphologic Relapse is defined as either reappearance of ≥ 5% blasts in the BM not attributable to any other cause or the development of extramedullary disease. Progression (PD) is defined as a > 50% increase of BM blast count percentage from baseline to ≥ 20% for participants with 5 to 70% BM blasts at baseline or a doubling of absolute blast count in peripheral blood from baseline to ≥ 10 x 109/L (10,000/μL) for participants with > 70% BM blasts at baseline or the development of new extramedullary disease.
Time Frame From first dose to end of study
Outcome Measure Data Not Reported
Time Frame From first dose up to approximately 26 Months
Adverse Event Reporting Description The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication.
 
Arm/Group Title Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Hide Arm/Group Description Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100 mg orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH2 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 200 mg, orally QD on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Participants with an IDH1 mutation receive Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-120 tablets was given at 500 mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine SC 75 mg/m2/day for 7 days of every 28-day treatment cycle was co-administered with AG-221 tablets given at 100mg orally once a day (QD) on Days 1 to 28 of each 28-day cycle. Azacitidine monotherapy was administered SC at 75 mg/m2/day for 7 days of every 28-day treatment cycle
All-Cause Mortality
Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/3 (33.33%)   1/3 (33.33%)   1/7 (14.29%)   6/16 (37.50%)   29/68 (42.65%)   14/33 (42.42%) 
Hide Serious Adverse Events
Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   2/3 (66.67%)   4/7 (57.14%)   11/16 (68.75%)   64/68 (94.12%)   25/32 (78.13%) 
Blood and lymphatic system disorders             
Anaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Febrile bone marrow aplasia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  3/68 (4.41%)  0/32 (0.00%) 
Febrile neutropenia † 1  1/3 (33.33%)  1/3 (33.33%)  1/7 (14.29%)  7/16 (43.75%)  26/68 (38.24%)  8/32 (25.00%) 
Hyperfibrinolysis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Hyperleukocytosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Leukocytosis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Pancytopenia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Thrombocytopenia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Thrombocytopenic purpura † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cardiac disorders             
Acute myocardial infarction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Atrial fibrillation † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Atrioventricular block complete † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Bundle branch block left † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cardiac arrest † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Coronary artery disease † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Myocardial ischaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Pericardial haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Supraventricular tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Endocrine disorders             
Hypopituitarism † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Gastrointestinal disorders             
Abdominal pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Colitis † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Diarrhoea † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  5/68 (7.35%)  0/32 (0.00%) 
Dysphagia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Gastrointestinal haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Haemorrhoidal haemorrhage † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Large intestine perforation † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Neutropenic colitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Salivary gland enlargement † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Stomatitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Upper gastrointestinal haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Volvulus of small bowel † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Vomiting † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  0/32 (0.00%) 
General disorders             
Catheter site thrombosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Death † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Fatigue † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
General physical health deterioration † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Influenza like illness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Medical device site pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Non-cardiac chest pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Pyrexia † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  3/16 (18.75%)  4/68 (5.88%)  2/32 (6.25%) 
Hepatobiliary disorders             
Bile duct stone † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cholecystitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Hyperbilirubinaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Immune system disorders             
Hypersensitivity † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Infections and infestations             
Anorectal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Bacteraemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Bacterial sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Bronchopulmonary aspergillosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cellulitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  2/68 (2.94%)  1/32 (3.13%) 
Chest wall abscess † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Clostridium difficile colitis † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Colonic abscess † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Coxsackie viral infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cystitis bacterial † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Device related infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Device related sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Diverticulitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Endocarditis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Enterobacter bacteraemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Enterococcal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Gastroenteritis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Gastrointestinal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Haemophilus sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Injection site cellulitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Lower respiratory tract infection fungal † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Lung infection † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  2/16 (12.50%)  7/68 (10.29%)  3/32 (9.38%) 
Neutropenic infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Neutropenic sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Oral infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Osteomyelitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Parainfluenzae virus infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Paronychia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Pneumonia † 1  1/3 (33.33%)  1/3 (33.33%)  2/7 (28.57%)  0/16 (0.00%)  7/68 (10.29%)  5/32 (15.63%) 
Pneumonia bacterial † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Pneumonia fungal † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Pneumonia influenzal † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Rectal abscess † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Respiratory syncytial virus infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Respiratory tract infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Scrotal abscess † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  8/68 (11.76%)  1/32 (3.13%) 
Septic shock † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Serratia bacteraemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Skin infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Soft tissue infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Staphylococcal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Streptococcal bacteraemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Superinfection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Tooth abscess † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Upper respiratory tract infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  2/32 (6.25%) 
Urinary tract infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  1/32 (3.13%) 
Urinary tract infection bacterial † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Urinary tract infection fungal † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Urosepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Vascular device infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Injury, poisoning and procedural complications             
Ankle fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Fall † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Femur fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Hip fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Hyphaema † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Spinal fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Subdural haematoma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Wrist fracture † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Investigations             
Blood alkaline phosphatase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Blood bilirubin increased † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  3/68 (4.41%)  0/32 (0.00%) 
Metabolism and nutrition disorders             
Dehydration † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Failure to thrive † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Hyperglycaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Hypokalaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Hyponatraemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Hypophosphataemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Muscular weakness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Rheumatoid arthritis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Synovial cyst † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Brain neoplasm † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Bronchioloalveolar carcinoma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Differentiation syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  3/16 (18.75%)  7/68 (10.29%)  0/32 (0.00%) 
Lung carcinoma cell type unspecified recurrent † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Metastases to meninges † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Nervous system disorders             
Altered state of consciousness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Cerebrovascular accident † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Depressed level of consciousness † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Nervous system disorder † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Presyncope † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Seizure † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Syncope † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Transient ischaemic attack † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Psychiatric disorders             
Mental status changes † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Renal and urinary disorders             
Acute kidney injury † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  0/32 (0.00%) 
Azotaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Nephrolithiasis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Urinary retention † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Reproductive system and breast disorders             
Vaginal haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Acute respiratory failure † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Dyspnoea † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Epistaxis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Interstitial lung disease † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Pleural effusion † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  0/32 (0.00%) 
Pneumonitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Pulmonary oedema † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Respiratory failure † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  1/32 (3.13%) 
Skin and subcutaneous tissue disorders             
Angioedema † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Rash maculo-papular † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Vascular disorders             
Circulatory collapse † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Deep vein thrombosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Embolism † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Hypertension † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Hypertensive crisis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Hypotension † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  1/32 (3.13%) 
1
Term from vocabulary, 22.0
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Phase 1b Dose-finding Stage: AG-221 (100mg) + AZA Phase 1b Dose-finding Stage: AG-221 (200mg) + AZA Phase 1b Dose-finding Stage: AG-120 (500mg) + AZA Phase 1b Expansion Stage: AG-120 (500mg) + AZA Phase 2 Randomized Stage: AG-221 (100mg) + AZA Phase 2 Randomized Stage: AZA Monotherapy
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/3 (100.00%)   3/3 (100.00%)   7/7 (100.00%)   16/16 (100.00%)   67/68 (98.53%)   32/32 (100.00%) 
Blood and lymphatic system disorders             
Anaemia † 1  1/3 (33.33%)  3/3 (100.00%)  3/7 (42.86%)  7/16 (43.75%)  35/68 (51.47%)  15/32 (46.88%) 
Bone marrow failure † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  3/68 (4.41%)  0/32 (0.00%) 
Coagulopathy † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Febrile bone marrow aplasia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Febrile neutropenia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  6/68 (8.82%)  1/32 (3.13%) 
Haemolysis † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Hyperleukocytosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Leukocytosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  6/68 (8.82%)  1/32 (3.13%) 
Leukopenia † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  1/16 (6.25%)  5/68 (7.35%)  1/32 (3.13%) 
Neutropenia † 1  0/3 (0.00%)  2/3 (66.67%)  2/7 (28.57%)  3/16 (18.75%)  31/68 (45.59%)  9/32 (28.13%) 
Pancytopenia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Splenomegaly † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Thrombocytopenia † 1  2/3 (66.67%)  2/3 (66.67%)  5/7 (71.43%)  7/16 (43.75%)  40/68 (58.82%)  14/32 (43.75%) 
Cardiac disorders             
Atrial fibrillation † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  2/68 (2.94%)  2/32 (6.25%) 
Atrial flutter † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Atrioventricular block complete † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Bradycardia † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Cardiac failure † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  1/32 (3.13%) 
Cardiomegaly † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Left ventricular hypertrophy † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Palpitations † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  0/68 (0.00%)  1/32 (3.13%) 
Pericarditis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Sinus arrhythmia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Sinus tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  1/68 (1.47%)  0/32 (0.00%) 
Supraventricular tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  2/32 (6.25%) 
Tachycardia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  4/68 (5.88%)  1/32 (3.13%) 
Ear and labyrinth disorders             
Ear pain † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Hypoacusis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  1/68 (1.47%)  0/32 (0.00%) 
Vertigo † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  4/68 (5.88%)  0/32 (0.00%) 
Endocrine disorders             
Hypothyroidism † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Eye disorders             
Conjunctival haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Lacrimation decreased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Periorbital swelling † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Vision blurred † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  1/32 (3.13%) 
Visual impairment † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  3/16 (18.75%)  0/68 (0.00%)  1/32 (3.13%) 
Gastrointestinal disorders             
Abdominal discomfort † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Abdominal distension † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Abdominal pain † 1  3/3 (100.00%)  1/3 (33.33%)  0/7 (0.00%)  4/16 (25.00%)  12/68 (17.65%)  5/32 (15.63%) 
Abdominal pain lower † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Abdominal pain upper † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  4/68 (5.88%)  0/32 (0.00%) 
Anal fistula † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Anal incontinence † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Colitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Constipation † 1  2/3 (66.67%)  1/3 (33.33%)  4/7 (57.14%)  7/16 (43.75%)  31/68 (45.59%)  15/32 (46.88%) 
Defaecation urgency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Diarrhoea † 1  1/3 (33.33%)  2/3 (66.67%)  5/7 (71.43%)  9/16 (56.25%)  29/68 (42.65%)  9/32 (28.13%) 
Dry mouth † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Dyspepsia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  2/32 (6.25%) 
Dysphagia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Flatulence † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Gastritis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Gastrooesophageal reflux disease † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Haematochezia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Haemorrhoids † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  4/68 (5.88%)  1/32 (3.13%) 
Ileus † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Lip swelling † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Melaena † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  1/68 (1.47%)  0/32 (0.00%) 
Mouth haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Mouth ulceration † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Nausea † 1  2/3 (66.67%)  2/3 (66.67%)  6/7 (85.71%)  8/16 (50.00%)  47/68 (69.12%)  12/32 (37.50%) 
Oral disorder † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Proctalgia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Rectal haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Small intestinal obstruction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Stomatitis † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  10/68 (14.71%)  1/32 (3.13%) 
Toothache † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  1/32 (3.13%) 
Vomiting † 1  1/3 (33.33%)  3/3 (100.00%)  1/7 (14.29%)  9/16 (56.25%)  33/68 (48.53%)  11/32 (34.38%) 
General disorders             
Asthenia † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  3/16 (18.75%)  16/68 (23.53%)  4/32 (12.50%) 
Catheter site pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Chest discomfort † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Chest pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  3/68 (4.41%)  2/32 (6.25%) 
Chills † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  4/68 (5.88%)  0/32 (0.00%) 
Facial pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Fatigue † 1  1/3 (33.33%)  1/3 (33.33%)  5/7 (71.43%)  4/16 (25.00%)  19/68 (27.94%)  8/32 (25.00%) 
Gait disturbance † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Granuloma † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Infusion site discomfort † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Infusion site reaction † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Injection site bruising † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Injection site erythema † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  3/16 (18.75%)  11/68 (16.18%)  7/32 (21.88%) 
Injection site haemorrhage † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Injection site irritation † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  2/32 (6.25%) 
Injection site pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  2/68 (2.94%)  3/32 (9.38%) 
Injection site pruritus † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Injection site reaction † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Injection site swelling † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Malaise † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  3/32 (9.38%) 
Mucosal inflammation † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Non-cardiac chest pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  6/68 (8.82%)  1/32 (3.13%) 
Oedema peripheral † 1  1/3 (33.33%)  1/3 (33.33%)  1/7 (14.29%)  4/16 (25.00%)  20/68 (29.41%)  10/32 (31.25%) 
Pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  4/68 (5.88%)  2/32 (6.25%) 
Peripheral swelling † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Pyrexia † 1  1/3 (33.33%)  2/3 (66.67%)  2/7 (28.57%)  5/16 (31.25%)  19/68 (27.94%)  6/32 (18.75%) 
Vessel puncture site haematoma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hepatobiliary disorders             
Cholelithiasis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Granulomatous liver disease † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hyperbilirubinaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  6/68 (8.82%)  0/32 (0.00%) 
Immune system disorders             
Drug hypersensitivity † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Immunodeficiency † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Infections and infestations             
Bacteraemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Bacterial infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Clostridium difficile infection † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Conjunctivitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Device related sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Enterococcal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Folliculitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  3/32 (9.38%) 
Fungal skin infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Influenza † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  2/68 (2.94%)  0/32 (0.00%) 
Lung infection † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  1/32 (3.13%) 
Mastoiditis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Mycobacterium avium complex infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Nasopharyngitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Oral candidiasis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Oral herpes † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  6/68 (8.82%)  0/32 (0.00%) 
Paronychia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Periodontitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Pneumonia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  2/32 (6.25%) 
Post procedural infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Sepsis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  0/68 (0.00%)  0/32 (0.00%) 
Sinusitis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Skin infection † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Staphylococcal infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  0/32 (0.00%) 
Upper respiratory tract infection † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  5/16 (31.25%)  2/68 (2.94%)  2/32 (6.25%) 
Urinary tract infection † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  11/68 (16.18%)  2/32 (6.25%) 
Viral upper respiratory tract infection † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Injury, poisoning and procedural complications             
Contusion † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  1/16 (6.25%)  1/68 (1.47%)  4/32 (12.50%) 
Fall † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Ligament sprain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Road traffic accident † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Skin abrasion † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Skin laceration † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  0/68 (0.00%)  0/32 (0.00%) 
Transfusion reaction † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Wound † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Investigations             
Alanine aminotransferase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  2/32 (6.25%) 
Amylase increased † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  0/16 (0.00%)  2/68 (2.94%)  1/32 (3.13%) 
Antithrombin III decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Blood alkaline phosphatase increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  5/68 (7.35%)  3/32 (9.38%) 
Blood bilirubin increased † 1  1/3 (33.33%)  3/3 (100.00%)  1/7 (14.29%)  1/16 (6.25%)  19/68 (27.94%)  1/32 (3.13%) 
Blood chloride decreased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Blood cholesterol increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Blood creatine phosphokinase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Blood creatinine increased † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  4/68 (5.88%)  3/32 (9.38%) 
Blood glucose increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Blood phosphorus increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Blood urea increased † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
C-reactive protein increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Carbon dioxide decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Carbon dioxide increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Electrocardiogram QT prolonged † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  7/16 (43.75%)  6/68 (8.82%)  1/32 (3.13%) 
Gamma-glutamyltransferase increased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  5/68 (7.35%)  1/32 (3.13%) 
International normalised ratio increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Lipase increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  1/32 (3.13%) 
Lymphocyte count decreased † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Neutrophil count decreased † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  2/68 (2.94%)  0/32 (0.00%) 
Platelet count decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  3/68 (4.41%)  0/32 (0.00%) 
Transaminases increased † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Weight decreased † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  6/68 (8.82%)  2/32 (6.25%) 
White blood cell count decreased † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
White blood cell count increased † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Metabolism and nutrition disorders             
Decreased appetite † 1  2/3 (66.67%)  0/3 (0.00%)  1/7 (14.29%)  5/16 (31.25%)  25/68 (36.76%)  1/32 (3.13%) 
Dyslipidaemia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Electrolyte imbalance † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Fluid overload † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Folate deficiency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Gout † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hypercalcaemia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Hyperglycaemia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  5/68 (7.35%)  0/32 (0.00%) 
Hyperkalaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  2/32 (6.25%) 
Hyperlipasaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hypernatraemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Hyperuricaemia † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/16 (0.00%)  7/68 (10.29%)  1/32 (3.13%) 
Hypervolaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hypoalbuminaemia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  5/68 (7.35%)  0/32 (0.00%) 
Hypocalcaemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  6/68 (8.82%)  0/32 (0.00%) 
Hypoglycaemia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Hypokalaemia † 1  1/3 (33.33%)  1/3 (33.33%)  3/7 (42.86%)  5/16 (31.25%)  25/68 (36.76%)  5/32 (15.63%) 
Hypomagnesaemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  3/16 (18.75%)  6/68 (8.82%)  1/32 (3.13%) 
Hyponatraemia † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  3/16 (18.75%)  1/68 (1.47%)  2/32 (6.25%) 
Hypophosphataemia † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  5/68 (7.35%)  2/32 (6.25%) 
Tumour lysis syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Vitamin B1 deficiency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Vitamin B12 deficiency † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Zinc deficiency † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Musculoskeletal and connective tissue disorders             
Arthralgia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  10/68 (14.71%)  3/32 (9.38%) 
Arthritis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Back pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  6/16 (37.50%)  12/68 (17.65%)  5/32 (15.63%) 
Bone pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  5/68 (7.35%)  1/32 (3.13%) 
Exostosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Flank pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Limb discomfort † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Muscle spasms † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Muscular weakness † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  1/68 (1.47%)  0/32 (0.00%) 
Musculoskeletal pain † 1  1/3 (33.33%)  1/3 (33.33%)  1/7 (14.29%)  0/16 (0.00%)  7/68 (10.29%)  1/32 (3.13%) 
Myalgia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  2/68 (2.94%)  1/32 (3.13%) 
Neck pain † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Pain in extremity † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  1/16 (6.25%)  8/68 (11.76%)  3/32 (9.38%) 
Rotator cuff syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Synovial cyst † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Tendonitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  0/68 (0.00%)  0/32 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Basal cell carcinoma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Benign lung neoplasm † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Benign neoplasm of skin † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Breast cancer recurrent † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Differentiation syndrome † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  1/16 (6.25%)  6/68 (8.82%)  0/32 (0.00%) 
Skin cancer † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Squamous cell carcinoma of skin † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Nervous system disorders             
Cognitive disorder † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  3/16 (18.75%)  0/68 (0.00%)  0/32 (0.00%) 
Dizziness † 1  0/3 (0.00%)  1/3 (33.33%)  3/7 (42.86%)  3/16 (18.75%)  17/68 (25.00%)  3/32 (9.38%) 
Dysgeusia † 1  2/3 (66.67%)  1/3 (33.33%)  0/7 (0.00%)  2/16 (12.50%)  5/68 (7.35%)  0/32 (0.00%) 
Headache † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  4/16 (25.00%)  14/68 (20.59%)  5/32 (15.63%) 
Hyperaesthesia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Hypersomnia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Lethargy † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Memory impairment † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Migraine with aura † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Neuropathy peripheral † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Paraesthesia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  0/32 (0.00%) 
Peripheral sensory neuropathy † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  4/68 (5.88%)  2/32 (6.25%) 
Restless legs syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Tremor † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  4/68 (5.88%)  0/32 (0.00%) 
Pregnancy, puerperium and perinatal conditions             
Cephalhaematoma † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Psychiatric disorders             
Anxiety † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  8/68 (11.76%)  3/32 (9.38%) 
Claustrophobia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Confusional state † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  3/68 (4.41%)  1/32 (3.13%) 
Delirium † 1  1/3 (33.33%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  1/68 (1.47%)  1/32 (3.13%) 
Depression † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  3/16 (18.75%)  4/68 (5.88%)  3/32 (9.38%) 
Hallucination † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Insomnia † 1  0/3 (0.00%)  0/3 (0.00%)  2/7 (28.57%)  4/16 (25.00%)  13/68 (19.12%)  3/32 (9.38%) 
Panic attack † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Renal and urinary disorders             
Acute kidney injury † 1  0/3 (0.00%)  1/3 (33.33%)  2/7 (28.57%)  1/16 (6.25%)  11/68 (16.18%)  0/32 (0.00%) 
Chronic kidney disease † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Dysuria † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  3/68 (4.41%)  0/32 (0.00%) 
Haematuria † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  2/32 (6.25%) 
Nephrolithiasis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Renal failure † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  0/32 (0.00%) 
Urinary retention † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Reproductive system and breast disorders             
Erectile dysfunction † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  0/68 (0.00%)  1/32 (3.13%) 
Prostatism † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Pruritus genital † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Cough † 1  0/3 (0.00%)  2/3 (66.67%)  2/7 (28.57%)  4/16 (25.00%)  13/68 (19.12%)  7/32 (21.88%) 
Dysphonia † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Dyspnoea † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  13/68 (19.12%)  4/32 (12.50%) 
Epistaxis † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  12/68 (17.65%)  3/32 (9.38%) 
Hypoxia † 1  0/3 (0.00%)  2/3 (66.67%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Nasal congestion † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  2/32 (6.25%) 
Oropharyngeal pain † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  2/16 (12.50%)  4/68 (5.88%)  2/32 (6.25%) 
Painful respiration † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Pleural effusion † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Pleurisy † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Productive cough † 1  0/3 (0.00%)  1/3 (33.33%)  0/7 (0.00%)  0/16 (0.00%)  2/68 (2.94%)  2/32 (6.25%) 
Rhinorrhoea † 1  0/3 (0.00%)  2/3 (66.67%)  1/7 (14.29%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Tachypnoea † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Upper-airway cough syndrome † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  2/32 (6.25%) 
Skin and subcutaneous tissue disorders             
Actinic keratosis † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Alopecia † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  1/32 (3.13%) 
Blister † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Dermal cyst † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Dermatitis acneiform † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Dermatitis bullous † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Dry skin † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Ecchymosis † 1  1/3 (33.33%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Erythema † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  3/68 (4.41%)  1/32 (3.13%) 
Erythema nodosum † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Hypersensitivity vasculitis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Night sweats † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  3/68 (4.41%)  1/32 (3.13%) 
Pain of skin † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  1/68 (1.47%)  0/32 (0.00%) 
Petechiae † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  4/68 (5.88%)  2/32 (6.25%) 
Pruritus † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  6/68 (8.82%)  3/32 (9.38%) 
Rash † 1  0/3 (0.00%)  1/3 (33.33%)  1/7 (14.29%)  0/16 (0.00%)  3/68 (4.41%)  1/32 (3.13%) 
Rash erythematous † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  1/16 (6.25%)  1/68 (1.47%)  0/32 (0.00%) 
Rash macular † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Rash maculo-papular † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  8/68 (11.76%)  1/32 (3.13%) 
Rash papular † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Rash pruritic † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Skin discomfort † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Urticaria † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  2/16 (12.50%)  1/68 (1.47%)  1/32 (3.13%) 
Vascular disorders             
Aortic thrombosis † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Flushing † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  0/68 (0.00%)  0/32 (0.00%) 
Haematoma † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  4/68 (5.88%)  1/32 (3.13%) 
Hypertension † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  5/68 (7.35%)  3/32 (9.38%) 
Hypotension † 1  2/3 (66.67%)  1/3 (33.33%)  1/7 (14.29%)  2/16 (12.50%)  13/68 (19.12%)  3/32 (9.38%) 
Orthostatic hypotension † 1  0/3 (0.00%)  0/3 (0.00%)  0/7 (0.00%)  1/16 (6.25%)  2/68 (2.94%)  0/32 (0.00%) 
Pallor † 1  1/3 (33.33%)  0/3 (0.00%)  0/7 (0.00%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
Thrombophlebitis superficial † 1  0/3 (0.00%)  0/3 (0.00%)  1/7 (14.29%)  0/16 (0.00%)  0/68 (0.00%)  0/32 (0.00%) 
1
Term from vocabulary, 22.0
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Bristol-Myers Squibb Study Director
Organization: Bristol-Myers Squibb
Phone: Please email:
EMail: Clinical.Trials@bms.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Celgene
ClinicalTrials.gov Identifier: NCT02677922    
Other Study ID Numbers: AG-221-AML-005
2015-003951-23 ( EudraCT Number )
First Submitted: February 5, 2016
First Posted: February 9, 2016
Results First Submitted: September 2, 2022
Results First Posted: November 22, 2022
Last Update Posted: January 25, 2024