Trial Outcomes & Findings for Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS) (NCT NCT01201811)

NCT ID: NCT01201811

Last Updated: 2019-12-05

Results Overview

Hematologic Response according to the 2000 International Working Group (IWG) response criteria for MDS was based on the Investigators determination and defined as: * Complete Response (CR): repeat bone marrow (BM) shows \<5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (\>110 g/L), neutrophils (≥1.5x10\^9/L), platelets (≥100x10\^9/L), blasts (0%) and no dysplasia * Partial Response (PR): same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment * Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months. * Failure: death during treatment or disease progression * Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence * Disease Progression: change in blast levels * Disease Transformation to AML

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 44 participants
• Primary outcome timeframe: Response assessed at end of cycle 6; through week 24; End of study
• Results posted on: 2019-12-05

Participant Flow

The study was conducted at nine investigational sites within Taiwan. The purpose of the current study was to evaluate the efficacy, safety, and steady-state Pharmacokinetic (PK) profile of subcutaneous (SC) azacitidine given at a dose of 75 mg/m^2/day for 7 days in Taiwanese participants with higher-risk Myelodysplastic Syndrome (MDS).

Participant milestones

Measure	Azacitidine Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Overall Study STARTED	44
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Measure	Azacitidine Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Overall Study Adverse Event	6
Overall Study Disease progression	3
Overall Study Withdrawal by Subject	3
Overall Study Death	4
Overall Study Treatment Failure	2
Overall Study Physician Decision	1

Baseline Characteristics

Study of Azacitidine in Adult Taiwanese Subjects With Higher-Risk Myelodysplastic Syndromes (MDS)

Baseline characteristics by cohort

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Age, Continuous	62.3 years STANDARD_DEVIATION 11.76 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants
Sex: Female, Male Male	27 Participants n=5 Participants
Race/Ethnicity, Customized Asian	44 Participants n=5 Participants
Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification Refractory anemia with excess blasts (RAEB)	35 Participants n=5 Participants
Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification RAEB in transformation	7 Participants n=5 Participants
Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification Chronic myelomonocytic leukemia (Modified CMML)	2 Participants n=5 Participants
Myelodysplastic Syndrome (MDS) French-American-British (FAB) Classification Acute myelogenous leukemia (AML)	0 Participants n=5 Participants
World Health Organization (WHO) Classification Refractory anemia with excess blasts (RAEB-1)	15 Participants n=5 Participants
World Health Organization (WHO) Classification Refractory anemia with excess blasts (RAEB-2)	23 Participants n=5 Participants
World Health Organization (WHO) Classification Acute myelogenous leukemia (AML)	5 Participants n=5 Participants
World Health Organization (WHO) Classification Chronic myelomonocytic leukemia (CMML -1)	1 Participants n=5 Participants
World Health Organization (WHO) Classification Chronic myelomonocytic leukemia (CMML-2)	0 Participants n=5 Participants
World Health Organization (WHO) Classification Refractory anemia (RA)	0 Participants n=5 Participants
World Health Organization (WHO) Classification RA with ringed sideroblasts (RARS)	0 Participants n=5 Participants
World Health Organization (WHO) Classification Refractory Cytopenia Multilineage Dysplasia (RCMD)	0 Participants n=5 Participants
World Health Organization (WHO) Classification Myelodysplastic Syndrome - Unclassified (MDS-U)	0 Participants n=5 Participants
International Prognostic Scoring System (IPSS) Low risk (0)	0 Participants n=5 Participants
International Prognostic Scoring System (IPSS) Intermediate-1 (0.5 - 1.0)	2 Participants n=5 Participants
International Prognostic Scoring System (IPSS) Intermediate-2 (1.5 - 2.0)	16 Participants n=5 Participants
International Prognostic Scoring System (IPSS) High Risk (≥ 2.5)	26 Participants n=5 Participants

PRIMARY outcome

Timeframe: Response assessed at end of cycle 6; through week 24; End of study

Population: The intention-to-treat (ITT) population was defined as all enrolled participants

Hematologic Response according to the 2000 International Working Group (IWG) response criteria for MDS was based on the Investigators determination and defined as:

• Complete Response (CR): repeat bone marrow (BM) shows <5% myeloblasts, and peripheral blood values lasting ≥ 2 months of hemoglobin (hgb) (>110 g/L), neutrophils (≥1.5x10^9/L), platelets (≥100x10^9/L), blasts (0%) and no dysplasia
• Partial Response (PR): same as CR for peripheral blood: BM shows blasts decrease by ≥ 50% or a less advanced FAB classification from pretreatment
• Stable disease (SD): failure to achieve a PR, no evidence of progression for at least 2 months.
• Failure: death during treatment or disease progression
• Relapse After CR or PR: return to pretreatment BM blast percent or decrement of ≥ 50% from remission/response levels in granulocytes or platelets; or reduction in hgb by ≥20 g/L or transfusion dependence
• Disease Progression: change in blast levels
• Disease Transformation to AML

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Overall (CR+PR+SD)	63.6 percentage of participants Interval 47.8 to 77.6
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Complete Remission (CR)	0.0 percentage of participants Interval 0.0 to 8.0
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Partial Remission (PR)	0.0 percentage of participants Interval 0.0 to 8.0
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Stable Disease (SD)	63.6 percentage of participants Interval 47.8 to 77.6
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Disease Progression (DP)	2.3 percentage of participants Interval 0.1 to 12.0
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Transformation to AML	4.5 percentage of participants Interval 0.6 to 15.5
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Failure	4.5 percentage of participants Interval 0.6 to 15.5
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator No Response Assessed	25.0 percentage of participants Interval 13.2 to 40.3
Percentage of Participants With a Hematologic Response Using International Working Group (IWG) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Investigator Overall (CR+PR)	0 percentage of participants Interval 0.0 to 8.0

PRIMARY outcome

Timeframe: Response assessed at end of cycle 6; through week 24; End of study

Population: The intention-to-treat (ITT) population was defined as all enrolled participants

Hematologic improvements (HI) have 4 categories:

1. Erythroid response (HI-E): Major >20g/L increase or transfusion independent. Minor- 10-20g/L increase or ≥50% decrease in transfusion requirements.

2. Platelet response (HI-P): Major absolute increase of ≥30x10^9/L or platelet transfusion independence. Minor-≥50% increase.

3. Neutrophil response (HI-N): Major 100% increase or an absolute increase of >0.5x10^9/L. Minor-≥100% increase and absolute increase of <0.5x10^9/L

4. Progression or relapse after HI

Overall hematological improvement (HI) was defined as any type (major or minor) of improvement of HI-E, HI-P, or HI-N. Criteria: Pretreatment=hemoglobin <100g/L or RBC transfusion-dependent, platelet count <100x10^9/L or platelet transfusion dependent, absolute neutrophil count <1.5x10^9/L. Sponsor's determination was derived using clinically relevant data.

Denominator for progression/relapse after HI included participants who had achieved HI.

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Any improvement	50.0 percentage of participants Interval 34.6 to 65.4
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-E (major)	31.8 percentage of participants Interval 18.6 to 47.6
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-E (minor)	9.1 percentage of participants Interval 2.5 to 21.7
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-P (major)	37.8 percentage of participants Interval 22.5 to 55.2
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-P (minor)	0 percentage of participants Interval 0.0 to 9.5
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-N (major)	7.1 percentage of participants Interval 0.9 to 23.5
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Hematologic Improvement-N (minor)	0 percentage of participants Interval 0.0 to 12.3
Percentage of Participants Showing Hematologic Improvement Using International Working Group (IWG Criteria for Hematologic Improvement Cheson 2000) Criteria for Myelodysplastic Syndrome (MDS) and Assessed by Sponsor Progression/relapse after HI	27.3 percentage of participants Interval 10.7 to 50.2

SECONDARY outcome

Timeframe: Up to week 24;The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: ITT Population- The intent-to-treat (ITT) population was defined as all enrolled participants.

The number of transfusions received 56 days prior to treatment and during study were standardized per 28 days and summarized by cycle for RBCs. The formula for standardizing per 28 days was: [(# of transfusions in the measurement period / length of the measurement period (days)) x 28], where the measurement period was either baseline or the relevant cycle length. For each participant the overall post-baseline average was calculated as the average of # of RBC transfusions per cycle.

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Number of Red Blood Cell (RBC) Transfusions by Cycle Baseline (N = 44)	1.3 Transfusions Standard Deviation 1.97
Number of Red Blood Cell (RBC) Transfusions by Cycle Overall Post-Baseline Average (N = 44)	2.4 Transfusions Standard Deviation 2.47
Number of Red Blood Cell (RBC) Transfusions by Cycle overall Change from Baseline ( N = 44)	1.0 Transfusions Standard Deviation 2.59
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 1 ( N = 44)	2.5 Transfusions Standard Deviation 2.27
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 2	2.3 Transfusions Standard Deviation 2.03
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 3	2.2 Transfusions Standard Deviation 2.90
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 4	1.5 Transfusions Standard Deviation 2.11
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 5	1.4 Transfusions Standard Deviation 2.59
Number of Red Blood Cell (RBC) Transfusions by Cycle Cycle 6	1.9 Transfusions Standard Deviation 3.96

SECONDARY outcome

Timeframe: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: The intent-to-treat (ITT) population was defined as all enrolled participants.

The number of transfusions received 56 days prior to treatment and during study was standardized per 28 days and summarized by cycle for platelets. The formula for standardizing per 28 days was: [(# of transfusions in the measurement period / length of the measurement period (days)) x 28], where the measurement period was either baseline or the relevant cycle length. For each participant the overall post-baseline average was calculated as the average of # of platelet transfusions per cycle.

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Number of Platelet Transfusions by Cycle Baseline ( N = 44)	0.9 Transfusions Standard Deviation 2.40
Number of Platelet Transfusions by Cycle Overall Post-Baseline Average ( N= 44)	2.7 Transfusions Standard Deviation 3.56
Number of Platelet Transfusions by Cycle OverallChange from Baseline ( N = 44)	1.8 Transfusions Standard Deviation 3.53
Number of Platelet Transfusions by Cycle Cycle 1 ( N = 44)	2.6 Transfusions Standard Deviation 3.38
Number of Platelet Transfusions by Cycle Cycle 2	2.3 Transfusions Standard Deviation 3.28
Number of Platelet Transfusions by Cycle Cycle 3	3.0 Transfusions Standard Deviation 4.85
Number of Platelet Transfusions by Cycle Cycle 4	1.6 Transfusions Standard Deviation 2.89
Number of Platelet Transfusions by Cycle Cycle 5	1.9 Transfusions Standard Deviation 3.61
Number of Platelet Transfusions by Cycle Cycle 6	2.7 Transfusions Standard Deviation 6.01

SECONDARY outcome

Timeframe: Up to week 24; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: The intent-to-treat (ITT) population was defined as all enrolled participants.

The on-treatment adverse event of infection requiring IV antibiotics, antifungals, or antivirals per 28 days/cycle. The overall post-baseline average is the average of number of infections requiring IV antibiotics or IV antiviral per 28 days/cycle. For each participant the overall post-baseline average was calculated as the average of # of infections requiring IV antibiotics or IV antiviral per 28 days per cycle.

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Baseline	0.1 Infections per cycle Standard Deviation 0.51
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Overall Post Baseline	0.5 Infections per cycle Standard Deviation 0.79
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Overall Change from Baseline	0.4 Infections per cycle Standard Deviation 0.98
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 1	0.5 Infections per cycle Standard Deviation 0.85
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 2	0.4 Infections per cycle Standard Deviation 0.61
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 3	0.4 Infections per cycle Standard Deviation 0.82
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 4	0.1 Infections per cycle Standard Deviation 0.39
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 5	0.1 Infections per cycle Standard Deviation 0.38
Number of Infections (Post-baseline Average) Requiring Intravenous Antibiotics, Anti-fungals, or Antivirals Per 28 Days Cycle 6	0.2 Infections per cycle Standard Deviation 0.66

SECONDARY outcome

Timeframe: From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)

Population: Safety Population included enrolled participants who received at least one dose of investigational product and had at least one postdose assessment

An AE that resulted in any of the following outcomes was defined as a serious adverse event (SAE):

• Death;
• Life-threatening event;
• Any inpatient hospitalization or prolongation of existing hospitalization;
• Persistent or significant disability or incapacity;
• Congenital anomaly or birth defect;
• Any other important medical event.

The severity of an AE was evaluated by the investigator according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) (Version 4.0) where Grade 1 = Mild, Grade 2 = Moderate, Grade 3 = Severe, Grade 4 = Life-threatening and Grade 5 = Death. Treatment Emergent AEs (TEAE) were defined as AEs with an onset date on or after the first dose of study drug and within 28 days after the date of the last dose. In addition, any AE that occurred beyond this timeframe and that was assessed by the investigator as possibly related to study drug was considered a TEAE.

Outcome measures

Measure	Azacitidine n=44 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Number of Participants With Adverse Events (AE) ≥ 1 TEAE	44 participants
Number of Participants With Adverse Events (AE) ≥ 1 NCI Grade 3 or 4 TEAE	37 participants
Number of Participants With Adverse Events (AE) ≥ TEAE related to study drug	34 participants
Number of Participants With Adverse Events (AE) ≥ 1 NCI Grade 3 or 4 TEAE related to study drug	22 participants
Number of Participants With Adverse Events (AE) ≥ 1 serious TEAE	28 participants
Number of Participants With Adverse Events (AE) ≥ 1 NCI CTC Grade 3 or 4 serious TEAE	24 participants
Number of Participants With Adverse Events (AE) ≥ 1 serious TEAE related to study drug	14 participants
Number of Participants With Adverse Events (AE) TEAE leading to discontinuation of study drug	8 participants
Number of Participants With Adverse Events (AE) TEAE leading to study drug dose reduction	7 participants
Number of Participants With Adverse Events (AE) TEAE leading to study drug dose interruption	16 participants
Number of Participants With Adverse Events (AE) TEAE leading to dose reduction or interruption	20 participants
Number of Participants With Adverse Events (AE) TEAE leading to death	7 participants

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

Area under the plasma concentration-time curve from time zero to infinity (AUC∞) following multiple doses of Azacitidine on Day 7; if possible, the area under the concentration-time curve from time zero to infinity, calculated by the linear trapezoidal rule and extrapolated to infinity was calculated according to the following equation: AUC∞ = AUCt + (Ct/ λz ), where Ct is the last quantifiable concentration. No AUC extrapolation was performed with unreliable λz. If % AUC extrapolated is ≥ 25%, AUC∞ was not reported.

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Area Under the Plasma Concentration-time Curve From Time Zero to Infinity (AUC∞) of Azacitidine	859.1 ng*h/mL Geometric Coefficient of Variation 23.4

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

Area under the plasma concentration-time curve from time zero to the last quantifiable time point, calculated by the linear trapezoidal rule when concentrations are increasing and the logarithmic trapezoidal method when concentrations are decreasing.

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Area Under the Plasma Concentration-time Curve From Time Zero to the Last Measurable Concentration (AUCt) of Azacitidine	852.8 ng*h/mL Geometric Coefficient of Variation 23.3

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

The observed maximum plasma concentration obtained directly from the observed concentration versus time data.

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Maximum Observed Plasma Concentration (Cmax) of Azacitidine	972.3 ng/mL Geometric Coefficient of Variation 44.0

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

Time to maximum observed plasma concentration obtained directly from the observed concentration versus time data.

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Time to Maximum Plasma Concentration (Tmax) of Azacitidine	0.29 hours Geometric Coefficient of Variation 27.65

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

The apparent terminal half-life was calculated according to the following equation t½ = 0.693/λz.

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Terminal Phase of Half-life (T1/2) of Azacitidine	1.0 hours Geometric Coefficient of Variation 38.7

SECONDARY outcome

Timeframe: Timeframe: Days 5 and 6 at predose and Day 7 (pre-dose) at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

Apparent total plasma clearance (CL/F) of Azacitidine was calculated as Dose/AUC∞

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Apparent Total Plasma Clearance (CL/F) of Azacitidine	149.6 L/hr Geometric Coefficient of Variation 29.6

SECONDARY outcome

Timeframe: Timeframe: Day 7 pre-dose and at 0.25, 0.5, 1, 2, 3, 4, 6, 8 hours post-dose

Population: The PK population includes all participants with evaluable azacitidine plasma PK profile.

Apparent volume of distribution, was calculated according to the equation: Vd/F = (CL/F)/λz

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Apparent Volume of Distribution (Vd/F) of Azacitidine	205.3 Liters Geometric Coefficient of Variation 32.4

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit

Population: The intent-to-treat (ITT) participants who were transfusion dependent

A participant was considered transfusion dependent at baseline if the participant had one or more Red Blood Cell transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no transfusions during any 56 consecutive days or more (e.g., Day 1 through 56, Day 2 through 57, etc). Otherwise, they were considered transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)

Outcome measures

Measure	Azacitidine n=32 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline Baseline Dependent: On-Treatment Independent	37.5 percentage of participants 95% Confidence Interval 1.97 • Interval 21.1 to 56.3
Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Dependent at Baseline Baseline Dependent; On-Treatment Dependent	62.5 percentage of participants 95% Confidence Interval 2.47 • Interval 43.7 to 78.9

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: The Intent to Treat (ITT) participants who were transfusion independent

A participant was considered RBC transfusion-independent at baseline if the participant had no RBC transfusions during the 56 days prior to first dose. During the study, a participant was considered transfusion independent during the on-treatment period if the participant had no RBC transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: RBC dependent at BL=32, RBC independent at BL=12)

Outcome measures

Measure	Azacitidine n=12 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline Baseline Independent; On-Treatment Independent	75.0 percentage of participants Interval 42.8 to 94.5
Participants' Red Blood Cell (RBC) Transfusion Status for Participants Who Were Transfusion Independent at Baseline Baseline Independent; On-Treatment Dependent	25.0 percentage of participants Interval 5.5 to 57.2

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: The intent-to-treat (ITT) population who were transfusion dependent

A participant was considered platelet transfusion dependent at baseline if the participant had one or more platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)

Outcome measures

Measure	Azacitidine n=18 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline Baseline Dependent; On-Treatment Independent	38.9 percentage of participants Interval 17.3 to 64.3
Participants' Platelet Transfusion Status for Participants Who Were Transfusion Dependent at Baseline Baseline Dependent; On-Treatment Dependent	61.1 percentage of participants Interval 35.7 to 82.7

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Cycle 6; The on-treatment period was considered the period from the date of the first dose to the last treatment study visit.

Population: The intent-to-treat (ITT) participants who were transfusion independent

A participant was considered platelet transfusion independent at baseline if the participant had no platelet transfusions during the 56 days prior to first dose. During the study, a participant was considered platelet transfusion independent during the on-treatment period if the participant had no platelet transfusions during any 56 consecutive days or more (eg, Days 1 through 56, Days 2 through 57, etc.). Otherwise, they were considered platelet transfusion dependent.

The total N=44, but 1 participant can only be dependent or independent at baseline for each type of transfusion (ie, total = 44: platelet dependent at BL=18, platelet independent at BL=26)

Outcome measures

Measure	Azacitidine n=26 Participants Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline Baseline Independent: On-Treatment Independent	76.9 percentage of particpants Interval 56.4 to 91.0
Participants' Platelet Transfusion Status for Participants Who Were Transfusion Independent at Baseline Baseline Independent; On-Treatment Dependent	23.1 percentage of particpants Interval 9.0 to 43.6

Adverse Events

Azacitidine

Serious events: 28 serious events

Other events: 44 other events

Deaths: 0 deaths

Serious adverse events

Measure	Azacitidine n=44 participants at risk Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Blood and lymphatic system disorders Thrombocytopenia	4.5% 2/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Anaemia	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Febrile neutropenia	22.7% 10/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Neutropenia	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Splenic infarction	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Cardiac disorders Cardiac arrest	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Cardiac disorders Cardiac failure congestive	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Caecitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Colitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Enteritis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Gastrointestinal haemorrhage	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Ileitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Pancreatitis acute	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Pyrexia	13.6% 6/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Hepatobiliary disorders Cholecystitis acute	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Hepatobiliary disorders Hepatic failure	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Abdominal infection	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Anal abscess	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Appendicitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Biliary tract infection	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Cellulitis	4.5% 2/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Enterobacter infection	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Epiglottitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Liver abscess	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Pneumonia	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Postoperative wound infection	4.5% 2/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Sepsis	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Septic shock	4.5% 2/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Soft tissue infection	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Subdiaphragmatic abscess	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Injury, poisoning and procedural complications Procedural pain	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Injury, poisoning and procedural complications Subdural haemorrhage	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Investigations Alanine aminotransferase increased	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Investigations Aspartate aminotransferase increased	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Hyperglycaemic hyperosmolar nonketotic syndrome	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Musculoskeletal and connective tissue disorders Muscular weakness	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute monocytic leukaemia	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Nervous system disorders Cerebellar haemorrhage	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Nervous system disorders Haemorrhage intracranial	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Nervous system disorders Sciatica	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Renal and urinary disorders Renal failure acute	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Pneumonia aspiration	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Respiratory failure	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Vascular disorders Hypotension	2.3% 1/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)

Other adverse events

Measure	Azacitidine n=44 participants at risk Azacitidine 75 mg/m\^2/day subcutaneously (SC) for 7 days every 28 days for up to 6 cycles
Blood and lymphatic system disorders Anaemia	43.2% 19/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Febrile neutropenia	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Leukopenia	43.2% 19/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Neutropenia	52.3% 23/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Blood and lymphatic system disorders Thrombocytopenia	36.4% 16/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Eye disorders Conjunctivitis	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Eye disorders Dry eye	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Abdominal distension	15.9% 7/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Abdominal pain upper	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Constipation	38.6% 17/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Diarrhoea	38.6% 17/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Dyspepsia	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Gingival bleeding	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Haemorrhoids	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Lip ulceration	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Melaena	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Mouth ulceration	15.9% 7/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Nausea	38.6% 17/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Stomatitis	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Gastrointestinal disorders Vomiting	38.6% 17/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Asthenia	13.6% 6/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Fatigue	20.5% 9/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Feeling cold	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Injection site pain	11.4% 5/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Malaise	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Non-cardiac chest pain	11.4% 5/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Oedema peripheral	13.6% 6/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
General disorders Pyrexia	52.3% 23/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Gingivitis	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Nasopharyngitis	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Oral candidiasis	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Periodontitis	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Infections and infestations Pneumonia	15.9% 7/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Injury, poisoning and procedural complications Allergic transfusion reaction	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Injury, poisoning and procedural complications Procedural pain	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Injury, poisoning and procedural complications Transfusion reaction	15.9% 7/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Investigations Alanine aminotransferase increased	13.6% 6/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Investigations Aspartate aminotransferase increased	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Investigations Weight decreased	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Decreased appetite	27.3% 12/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Haemochromatosis	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Hypoalbuminaemia	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Hypocalcaemia	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Hypokalaemia	29.5% 13/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Metabolism and nutrition disorders Hyponatraemia	11.4% 5/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Musculoskeletal and connective tissue disorders Myalgia	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Musculoskeletal and connective tissue disorders Pain in extremity	11.4% 5/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Nervous system disorders Dizziness	38.6% 17/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Nervous system disorders Headache	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Psychiatric disorders Insomnia	20.5% 9/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Renal and urinary disorders Haematuria	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Cough	50.0% 22/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.2% 8/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	13.6% 6/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Epistaxis	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Nasal congestion	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Pleural effusion	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Productive cough	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	22.7% 10/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Skin and subcutaneous tissue disorders Ecchymosis	15.9% 7/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Skin and subcutaneous tissue disorders Petechiae	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Skin and subcutaneous tissue disorders Pruritus	25.0% 11/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Skin and subcutaneous tissue disorders Rash	20.5% 9/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Skin and subcutaneous tissue disorders Rash pruritic	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Vascular disorders Hypertension	9.1% 4/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)
Vascular disorders Hypotension	6.8% 3/44 • From the first dose of study drug through 28 days after completion of/discontinuation from the study (maximum time on study drug 244 days)

Additional Information

Anne McClain

Celgene Corporation

Phone: 1-888-260-1599

Email: clinicaltrialdisclosure@celgene.com

Results disclosure agreements

• Principal investigator is a sponsor employee Multicenter publication must include input from all Investigators involved in the study and Sponsor before its publication; it has priority over subset (single center) publication during 1 year after study completion; Each Investigator has publication rights after multicenter publication is submitted or 1 year after study completion. Sponsor has the right to comment on the publication and ask for a 90-day delay to protect its intellectual property and/or deletion of any confidential information.
• Publication restrictions are in place

Restriction type: OTHER