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The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

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ClinicalTrials.gov Identifier: NCT01566695
Recruitment Status : Active, not recruiting
First Posted : March 29, 2012
Results First Posted : February 26, 2020
Last Update Posted : February 26, 2020
Sponsor:
Information provided by (Responsible Party):
Celgene

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Myelodysplastic Syndrome
Interventions Drug: Oral Azacitidine
Drug: Placebo
Other: Best Supportiv Care (BSC)
Enrollment 216
Recruitment Details Participants were randomized at 101 sites globally. The sites were located in: Europe (76), North America (13), Asia/Pacific (10), and Latin America (2). Results are reported as of the data cut-off date of 25 January 2019.
Pre-assignment Details Participants were stratified by: average baseline (BL) Red Blood Cell (RBC) transfusion requirement (≤ 4 units versus > 4 units of RBC per 28 days), BL platelet transfusion status (dependent or independent), country of enrollment and Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) (0 to 1 versus 2).
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections. Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Period Title: Overall Study
Started 107 109
Completed [1] 12 10
Not Completed 95 99
Reason Not Completed
Lack of Efficacy             18             45
Adverse Event             28             27
Death             20             8
Withdrawal by Subject             14             7
Progressive Disease             11             6
Miscellaneous             4             6
[1]
Completed = participants on treatment as of data cut off date of 25 Jan 2019
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care Total
Hide Arm/Group Description Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections. Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections. Total of all reporting groups
Overall Number of Baseline Participants 107 109 216
Hide Baseline Analysis Population Description
The intent-to-treat (ITT) population included all participants who were randomized, regardless of whether they received treatment or not.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 107 participants 109 participants 216 participants
73.0  (9.23) 73.1  (8.36) 73.0  (8.78)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
Female
28
  26.2%
30
  27.5%
58
  26.9%
Male
79
  73.8%
79
  72.5%
158
  73.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
White
96
  89.7%
99
  90.8%
195
  90.3%
Black or African American
1
   0.9%
0
   0.0%
1
   0.5%
Asian
2
   1.9%
3
   2.8%
5
   2.3%
Native Hawaiian or Other Pacific Islanders
0
   0.0%
0
   0.0%
0
   0.0%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Japanese
0
   0.0%
0
   0.0%
0
   0.0%
Other
8
   7.5%
7
   6.4%
15
   6.9%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
Hispanic or Latino
4
   3.7%
9
   8.3%
13
   6.0%
Not Hispanic or Latino
91
  85.0%
93
  85.3%
184
  85.2%
Not Reported
12
  11.2%
7
   6.4%
19
   8.8%
Myelodysplastic Syndrome (MDS) World Health Organization (WHO) 2008 Classification   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
RA = Refractory Anemia
4
   3.7%
3
   2.8%
7
   3.2%
RN = Refractory Neutropenia
0
   0.0%
0
   0.0%
0
   0.0%
RT = Refractory Thrombocytopenia
1
   0.9%
0
   0.0%
1
   0.5%
RARS = RA with Ringed Sideroblasts
3
   2.8%
2
   1.8%
5
   2.3%
RCMD = R Cytopenia w/ Multilineage Dysplasia
80
  74.8%
73
  67.0%
153
  70.8%
RAEB-1 RA with Excess Blasts - 1
17
  15.9%
29
  26.6%
46
  21.3%
RAEB-2 RA with Excess Blasts - 2
0
   0.0%
0
   0.0%
0
   0.0%
MDS-U (MDS-unclassified)
2
   1.9%
2
   1.8%
4
   1.9%
del (5q) MDS Associated with Isolated del 5q
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The WHO classification recognizes eight subtypes of MDS that are distinguished by the percentage of myeloblasts, presence or absence of ringed sideroblasts (i.e., erythroid precursors with iron deposits surrounding the nucleus), presence of a monocytosis or a deletion 5q.
International Prognostic Scoring System (IPSS)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
Low
0
   0.0%
0
   0.0%
0
   0.0%
Intermediate 1 (0..5-1.0)
106
  99.1%
109
 100.0%
215
  99.5%
Intermediate 2 (1.5-2.0)
1
   0.9%
0
   0.0%
1
   0.5%
High
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: The international prognostic scoring system (IPSS) is a standard for risk assessment in primary myelodysplastic syndromes (MDS) that categorizes prognoses taking into account cytogenetics, cytopenias, blasts and blood counts. The IPSS prognostic subgroups consist of low-, intermediate-1-, intermediate-2-, and high-risk groups. The scale is 0-3.5 at 0.5 increments. Scores of 0=Low; 0.5-1.0=Int-1; 1.5-2.0=Int-2; 2.5-3.5=High risk which corresponds to poorer prognosis.
Average Red Blood Cell Transfusion Requirement (units per 28 days)   [1] 
Median (Full Range)
Unit of measure:  Units per 28 days
Number Analyzed 107 participants 109 participants 216 participants
3.33
(1.3 to 10.0)
3.33
(1.3 to 9.5)
3.33
(1.3 to 10.0)
[1]
Measure Description: The average red blood cell (RBC) transfusion units per 28 days is derived using transfusion records before randomization date to randomization date - 84 days (if enrolled under original protocol or protocol amendment 1), or to randomization date - 56 days (if enrolled under protocol 2).
Hemoglobin  
Mean (Standard Deviation)
Unit of measure:  g/dL
Number Analyzed 107 participants 109 participants 216 participants
8.22  (0.988) 8.04  (0.960) 8.13  (0.976)
Platelet Count  
Mean (Standard Deviation)
Unit of measure:  10^9 cells/L
Number Analyzed 107 participants 109 participants 216 participants
27.0  (15.97) 27.9  (18.11) 27.5  (17.05)
Platelet Transfusion Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
Dependent
30
  28.0%
35
  32.1%
65
  30.1%
Independent
77
  72.0%
74
  67.9%
151
  69.9%
[1]
Measure Description: Participants with thrombocytopenia were defined by 2 platelet counts that were ≤ 75 × 10^9/cells/L with a platelet measurement ≥ 21 days apart. For those who were platelet transfusion-dependent at baseline and did not achieve platelet transfusion independence (TI) ≥ 56 days (8 weeks) during study treatment were considered as non-responders. For participants who were not platelet transfusion-dependent at baseline, development of platelet transfusion dependence, ie, ≥ 2 platelet transfusions in any 56-day (8 week) period during study treatment and were considered worse outcome.
Eastern Cooperative Oncology Group (ECOG) Performance Status   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 107 participants 109 participants 216 participants
Grade 0-1
91
  85.0%
94
  86.2%
185
  85.6%
Grade 2
16
  15.0%
15
  13.8%
31
  14.4%
Grade 3
0
   0.0%
0
   0.0%
0
   0.0%
Grade 4
0
   0.0%
0
   0.0%
0
   0.0%
Grade 5
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Description: ECOG performance status is used to describe a patient’s level of functioning in terms of their ability to care for themselves, daily activity, and physical ability (walking, working, etc.). The scale ranges from 0 to 5: 0 = Fully active, no restrictions; 1 = Restricted activity but ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out work activities; 3 = Capable to only limited self-care, confined to bed or chair more than 50% of waking hours; 4 = Completely disabled, no self-care, confined to bed or chair; 5 = Dead.
1.Primary Outcome
Title Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence for ≥ 56 Days
Hide Description RBC transfusion (tfx) independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 56 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 56 days (i.e., day 1 to day 56, day 2 to day 57) were considered as a 56-day RBC transfusion independent responder.
Time Frame Each participant was assessed for at least 56 days or more; from the date of randomization of study drug up to the data cut-off date of 25 January 2019, approximately 5 months.
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population included all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
30.8
(22.1 to 39.6)
11.9
(5.8 to 18.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments 2 sided
Method Stratified Mantel-Haenszel Chi-squared
Comments Stratified by average baseline (BL) RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 18.9
Confidence Interval (2-Sided) 95%
8.3 to 29.6
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days
Hide Description Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 56 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 56 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In the event a participant had more than one ≥56 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis. Participants who maintained RBC TI through the end of the treatment period were censored at the date of treatment discontinuation, death, or 1 day before the start of the subsequent MDS treatment (if any), whichever occurred first, or the particiapnts latest available assessment date in the database if the treatment was still on-going.
Time Frame From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population. Participants who achieved RBC transfusion independence of ≥ 56 days on treatment.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 33 13
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(8.2 to 26.0)
12.0 [1] 
(2.3 to NA)
[1]
Could not be estimated due to the low number of events at the time of the analysis.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7547
Comments [Not Specified]
Method Two-sided Unstratified Log Rank Test
Comments [Not Specified]
3.Secondary Outcome
Title Time to RBC Transfusion Independence for at Least 56 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 56 Days
Hide Description Time to RBC transfusion independence of ≥ 56 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 56 without any RBC transfusions).
Time Frame From the date of randomization of study drug up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who achieved a 56-day TI response. Responders in the intent to treat population.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 33 13
Median (Full Range)
Unit of Measure: Months
2.37
(0.0 to 10.9)
2.04
(0.0 to 14.3)
4.Secondary Outcome
Title Duration of RBC Transfusion Reduction for Participants Who Achieved RBC Transfusion Reduction of at Least 4 Units of RBCs for at Least 8 Weeks
Hide Description A participant was considered as a RBC transfusion reduction responder if the participant had at least 4 units reduction in transfusion units over any consecutive 56 days period compared to the baseline transfusion units in 56 days.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population; includes participants who achieved RBC transfusion reduction of at least 4 units for at least 8 weeks.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 45 34
Median (95% Confidence Interval)
Unit of Measure: months
10.0
(7.1 to 13.3)
2.3
(2.0 to 5.0)
5.Secondary Outcome
Title Percentage of Participants Who Achieved Red Blood Cell Transfusion Independence for ≥ 84 Days
Hide Description RBC transfusion independence was defined as the absence of any RBC transfusion during any consecutive "rolling" 84 days within the treatment period. Participants who did not receive any RBC transfusion during a consecutive rolling 84 days (i.e., day 1 to day 84, day 2 to day 85) were considered as a 84-day RBC transfusion independent responder.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population includes all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
28.0
(19.5 to 36.5)
6.4
(1.8 to 11.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 2 sided
Method Stratified Mantel-Haenszel; Chi-squared
Comments Stratified by average BL RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 21.6
Confidence Interval (2-Sided) 95%
11.9 to 31.3
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Duration of RBC Transfusion Independence Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days
Hide Description Duration of RBC transfusion independence was analyzed only for participants who achieved RBC transfusion independence of ≥ 84 days on treatment. Duration of RBC transfusion independence was defined as the time from the date transfusion independence is first observed (day 1 of a ≥ 84 days period without a transfusion) until the date the participants had a subsequently documented RBC transfusion. In case a participant had more than one ≥84 days rolling periods which met the RBC independence criteria, the duration with the longest rolling period was used in the analysis.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population. Participants who achieved RBC transfusion independence for at least 84 days on treatment.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 30 7
Median (95% Confidence Interval)
Unit of Measure: months
11.1
(8.2 to 26.0)
NA [1] 
(5.0 to NA)
[1]
Could not be estimated due to the low number of events at the time of analysis.
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4347
Comments [Not Specified]
Method Two-Sided Unstratified Log Rank Test
Comments [Not Specified]
7.Secondary Outcome
Title Time to RBC Transfusion Independence for at Least 84 Days Among Participants Who Achieved RBC Transfusion Independence for at Least 84 Days
Hide Description Time to RBC transfusion independence of ≥ 84 days was defined as the time between randomization and the date onset of transfusion independence was first observed (ie, Day 1 of 84 without any RBC transfusions).
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who achieved a 84-day TI response. Responders in the intent to treat population.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 30 7
Median (Full Range)
Unit of Measure: Months
2.64
(0.0 to 9.9)
4.01
(0.5 to 14.3)
8.Secondary Outcome
Title Percentage of Participants With an Erythroid Hematological Improvement (HI-E) Response According to 2006 IWG Criteria
Hide Description Erythroid HI-E improvement was defined as a hemoglobin increase of ≥ 1.5 g/dL; or a reduction in units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of ≤ 9.0 g/dL on treatment were counted in the RBC transfusion response evaluation.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
HI-E Response
43.0
(33.6 to 52.4)
32.1
(23.3 to 40.9)
≥ 1.5 g/dL Hemoglobin Increase
23.4
(15.3 to 31.4)
5.5
(1.2 to 9.8)
RBC Transfusion Reduction
42.1
(32.7 to 51.4)
31.2
(22.5 to 39.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments HI-E
Statistical Test of Hypothesis P-Value 0.1467
Comments [Not Specified]
Method Stratified Mantel-Haenszel. Chi-squared
Comments Stratified by average BL RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
-2.0 to 23.7
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments ≥ 1.5 g/dL Hemoglobin Increase
Statistical Test of Hypothesis P-Value 0.0002
Comments [Not Specified]
Method Stratified Mantel-Haenszel. Chi-squared
Comments Stratified by average BL RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Diffrence
Estimated Value 17.9
Confidence Interval (2-Sided) 95%
8.8 to 26.9
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments RBC Transfusion Reduction
Statistical Test of Hypothesis P-Value 0.1431
Comments [Not Specified]
Method Stratified Mantel-Haenszel. Chi-squared
Comments Stratified by average BL RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 10.9
Confidence Interval (2-Sided) 95%
-1.9 to 23.6
Estimation Comments [Not Specified]
9.Secondary Outcome
Title Percentage of Participants With a Hematological Improvement Response in Platelets (HI-P) According to 2006 IWG Criteria
Hide Description HI-P response was defined according to IWG 2006 criteria (Cheson, 2006) and as: 1. Absolute increase of ≥ 30 X 10^9/L for participants^ starting with > 20 X 10^9/L platelets; 2. Increase from < 20 X 10^9/L to > 20 X 10^9/L and by at least 100%. HI-P must have lasted at least 8 weeks.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT population included all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
24.3
(16.2 to 32.4)
7.3
(2.4 to 12.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0007
Comments [Not Specified]
Method Stratified Mantel-Haenszel. Chi-squared
Comments Stratified by average BL RBC tfx needs: ≤4 units versus >4 units; BL platelet tfx status: dependent or independent and ECOG PS: 0 to 1 vs 2
Method of Estimation Estimation Parameter Rate Difference
Estimated Value 17.0
Confidence Interval (2-Sided) 95%
7.5 to 26.4
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Percentage of Participants Who Achieved Platelet Transfusion Independence With a Duration of ≥ 8 Weeks (56 Days)
Hide Description Platelet transfusion independence was defined as the absence of any platelet transfusion during any consecutive "rolling" 56 days during the treatment period, (ie, Day 1 to 56, Day 2 to 57, Days 3 to 58, etc.). Participants were considered platelet transfusion dependent at baseline if they had received ≥ 2 platelet transfusions during the 56 days immediately preceding randomization and had no consecutive 28-day period during which no platelet transfusions were administered.
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population; includes participants were were platelet transfusion dependent.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 30 35
Measure Type: Number
Unit of Measure: Percentage Participants
16.7 14.3
11.Secondary Outcome
Title Time to Platelet Transfusion Independence
Hide Description Time to platelet transfusion independence was defined as the time between randomization and the first documented date of onset of transfusion independence (ie, Day 1 of 56 without any platelet transfusions).
Time Frame From the date of randomization of study drug up to the treatment period; up to the data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Intent to Treat population; includes participants who achieved platelet transfusion independence for at least 56 days.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 5 5
Median (Full Range)
Unit of Measure: Months
2.04
(0.5 to 10.9)
1.48
(0.1 to 4.7)
12.Secondary Outcome
Title Kaplan-Meier Estimate of Overall Survival (OS)
Hide Description Overall survial was defined as the time from randomization to death from any cause, and was calculated using randomization date and date of death, or date of last follow-up for censored participants. All subjects were followed until drop out (withdrawal of consent from further data collection or lost to follow-up), death, or study closure. Participants who dropped out or were alive at study closure (or at the time of the interim analysis) had their OS times censored at the time of last contact, as appropriate. Overall survival was assessed as an interim analysis at the time of the primary analysis.
Time Frame From randomization to death from any cause; up to the data cut-off of date of 25 January 2019; maximum follow-up time for all participants was 67.9 months for the oral azacitidine arm and 64.8 months for placebo arm
Outcome Measure Data Not Reported
13.Secondary Outcome
Title Percentage of Participants With a Hematologic Response According to the 2006 IWG Criteria for MDS
Hide Description

Hematologic response was defined as:

  • A complete response (CR): <5% myeloblasts, and normal maturation of all cell lines; Peripheral blood (PB) shows: hemoglobin >10 g/dL, neutrophils ≥1.0x10^9/L, platelets ≥100x10^9/dL, blasts (0%)
  • Partial Response (PR): same as CR bone marrow (BM) shows blasts decreased by ≥ 50% over pre-treatment but still > 5%; Cellularity and morphology not relevant
  • Marrow CR: BM: ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment PB
  • Stable disease (SD): failure to achieve at least PR, but no evidence of progression for > 8 wks
  • Failure: death during treatment or disease progression
  • Disease Progression for those with:

    • Less than 5% blasts: ≥ 50% increase in blasts to > 5% blasts
    • 5%-10% blasts:≥ 50% increase to > 10% blasts
    • 10%-20% blasts:≥ 50% increase to > 20% blasts
    • 20%-30% blasts ≥ 50% increase to > 30% blasts

Any of the following:

  • ≥ 50% decrease from maximum remission/response in granulocytes or platelets
Time Frame Response was assessed every 3 cycles; up to the data cut-off date of 25 Jan 2019; median duration of exposure to oral azacitidine was 86.0 days and 119.0 days for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
Population includes participants with a CR, PR and mCR who had baseline bone marrow blasts > 5%. ITT population.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Unit of Measure: Percentage of Participants
Complete Response (CR) 7.7 0
Partial Response 0 0
Marrow CR 23.1 4.2
Stable Disease (SD) 2.8 30.3
Disease Progression 62.6 46.8
Failure due to Death 0.9 0.9
14.Secondary Outcome
Title Percentage of Participants Who Progressed to Acute Myeloid Leukemia (AML)
Hide Description Participants with a documented diagnosis of AML arising from previous MDS documented diagnosis.
Time Frame From randomization of study drug to the end up to final data cut-off date of 25 January 2019; maximum follow-up time was 67.9 months for azacitidine and 64.8 months for placebo group
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population included all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Unit of Measure: Percentage of Participants
7.5 16.5
15.Secondary Outcome
Title Time to Progression to Acute Myeloid Leukemia (AML) Among Participants Who Progressed to AML
Hide Description Time to AML progression was defined as the time from the date of randomization until the date the subject has documented progression to AML. For participants who had progression to AML documented in MLL central lab report, the earliest sample collection date with the diagnosis of "s-AML arising from previous MDS" was used as the date to AML progression.
Time Frame From randomization of study drug to progression of AML; up to final data cut-off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population who progressed to AML.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 8 18
Median (Full Range)
Unit of Measure: Months
17.94
(0.8 to 32.9)
9.91
(1.0 to 35.2)
16.Secondary Outcome
Title Percentage of Participants With Significant Bleeding Events
Hide Description Clinically significant bleeding event was defined as: any intracranial or retroperitoneal bleed; bleeding requiring transfusions of > 2 units of blood/blood products; bleeding associated with a decrease in hemoglobin of > 2 g/dL; or bleeding from any site requiring transfusions of > 2 units of blood.
Time Frame From date of randomization until 28 days after the last dose of IP; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The intent-to-treat (ITT) population included all participants who were randomized, regardless of whether they received treatment or not.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Unit of Measure: Percentage of Participants
8.4 9.2
17.Secondary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAE)
Hide Description

A TEAE was defined as an adverse event that begins or worsens in intensity of frequency on or after the first dose of study drug through 28 days after last dose of study drug.

A serious adverse event (SAE) is any:

  • 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 investigator determined the relationship of an AE to study drug based on the timing of the AE relative to drug administration and whether or not other drugs, therapeutic interventions, or underlying conditions could provide a sufficient explanation for the 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.
Time Frame From first dose of IP up to 28 days after the last dose of IP; up to data cut-off date of 25 Jan 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all randomized participants who received at least one dose of study drug.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Count of Participants
Unit of Measure: Participants
≥ 1 TEAE
107
 100.0%
108
  99.1%
≥ 1 TEAE Related to Study Drug
102
  95.3%
54
  49.5%
≥ 1 Serious TEAE
79
  73.8%
69
  63.3%
≥ 1 Serious TEAE Related to Study Drug
37
  34.6%
8
   7.3%
≥ 1 Grade (GR) 3-4 TEAE
96
  89.7%
80
  73.4%
≥ 1 Grade 3-4 TEAE Related to Study Drug
73
  68.2%
19
  17.4%
≥ 1 Grade (GR) 3-4 Serious TEAE
75
  70.1%
56
  51.4%
≥ 1 GR 3-4 Serious TEAE Related to Study Drug
37
  34.6%
5
   4.6%
≥ 1 TEAE Leading to Death
25
  23.4%
14
  12.8%
≥ 1 TEAE Related to Study Drug Leading to Death
9
   8.4%
2
   1.8%
≥ 1 TEAE Leading to Dose Reduction
31
  29.0%
4
   3.7%
≥ 1 TEAE Leading to Dose Interruption
66
  61.7%
40
  36.7%
≥ 1 TEAE Leading to Dose Interruption/Reduction
29
  27.1%
2
   1.8%
≥ 1 TEAE Leading to Treatment Discontinuation
32
  29.9%
31
  28.4%
18.Secondary Outcome
Title Mean Change From Baseline in the Physical Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia (FACT-An) Endpoints at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
0.2  (4.12) -0.8  (3.91)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.214
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
19.Secondary Outcome
Title Mean Change From Baseline in the Social Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
-0.4  (3.96) -1.1  (4.69)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.446
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
20.Secondary Outcome
Title Mean Change From Baseline in the Emotional Well-Being Component of the Functional Assessment of Cancer Therapy-Anemia Instrument at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
1.3  (4.33) 0.2  (4.35)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.248
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
21.Secondary Outcome
Title Mean Change From Baseline in the Functional Well-Being Component of the FACT-An Instrument at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The FACT-Anemia evaluable population was defined as all ITT participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
0.5  (3.95) -1.2  (4.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.058
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
22.Secondary Outcome
Title Mean Change From Baseline in the Anemia Subscale Within FACT-An Instrument at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
2.9  (11.81) -0.6  (10.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.130
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
23.Secondary Outcome
Title Mean Change From Baseline in the Fatigue-Related Subscale Within the FACT-An Instrument at Cycle 6
Hide Description The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being (PWG), social/family (SWB), emotional well being (EWB) and Functional Well-Being (FWB) and an additional 20-item anemia questionnaire that measures fatigue associated items and 7 non-fatigue items. The scales are formatted on 1 to 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general health related quality of life (HRQoL), the FACT-An measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various therapeutic areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 indicates the poorest QOL and 100 denotes the highest QOL.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
2.1  (8.74) -0.6  (7.84)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.123
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
24.Secondary Outcome
Title Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index (FACT-An TOI) Summary Scale Within the FACT-An Instrument at Cycle 6
Hide Description The FACT-G and FACT-An score are summed to form the FACT-An total score. The FACT-An Trial Outcome Index (TOI) consists of the summation of a "summary scale" and includes the Physical Well-being, (PWB; 7 items; score range, 0-28), the Functional Well-being (7 items; score range, 0-28) and the Anemia subscale consisting of 20 items on the same five-point scale, with 13 of them measuring fatigue related symptoms (FS) and seven measuring non-FS. The FACT-An TOI has been demonstrated to be a sensitive indicator of clinical outcomes in a number of diseases including MDS. The Fact-TOI score ranges from 0 to 136. Higher scores on all scales of the Fact-An and subscales on the FACT-TOI reflect better quality of life or fewer symptoms.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
3.7  (17.29) -2.7  (15.45)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.069
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
25.Secondary Outcome
Title Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General (FACT-G) Summary Scale Within the FACT-An Instrument at Cycle 6
Hide Description

The FACT-An is a 47-item, cancer-specific questionnaire consisting of a core 27-item general questionnaire (i.e., the Functional Assessment of Cancer Therapy-General [FACT-G]) The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are:

  • Physical Well-being (PWB; 7 items; score range, 0-28),
  • Social/Family Well-being (SWB; 7 items; score range, 0-28),
  • Emotional Well-being (EWB; 6 items; score range, 0-24), and
  • Functional Well-being (7 items; score range, 0-28). The FACT-G is a summation composed of a "summary scale" including the PWB, SWB, EWB and FWB. The FACT-G score range is from 0 to 108. For all summary scales including FACT-G, a higher score indicates better HRQoL or lower level of symptoms.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
1.6  (12.00) -2.9  (12.11)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.078
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
26.Secondary Outcome
Title Mean Change From Baseline in the Functional Assessment of Cancer Therapy-Anemia-Total Score at Cycle 6
Hide Description

The FACT-G and the anemia subscale (AnS) are summed to form the FACT-An total score and the total score ranges from 0 to 188. The FACT-G measures the 4 domains on a 5-point scale ranging from 0 (not at all) to 4 (very much). The 4 domains are:

  • Physical Well-being (PWB; 7 items; score range, 0-28),
  • Social/Family Well-being (SWB; 7 items; score range, 0-28),
  • Emotional Well-being (EWB; 6 items; score range, 0-24), and
  • Functional Well-being (7 items; score range, 0-28). The AnS consists of 20 items on the same 5-point scale, with 13 of them measuring fatigue-related symptoms (FS) and 7 measuring non-FS. The AnS and FS scores can range from 0-80 and 0-52, respectively. For all domains and summary subscales, a higher score indicates better HRQoL or lower level of symptoms.
Time Frame Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 42 49
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
4.5  (21.88) -3.5  (20.62)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.073
Comments [Not Specified]
Method t-test, 2 sided
Comments The p-value was calculated based on a pooled 2-sample, 2-sided t-test for the difference in mean change from baseline between treatment groups.
27.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Physical Well-Being Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
17.3 13.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.560
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Raatio
Estimated Value 0.77
Confidence Interval (2-Sided) 95%
0.54 to 1.30
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
28.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Social Well-Being Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
11.1 14.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.480
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Raatio
Estimated Value 0.72
Confidence Interval (2-Sided) 95%
0.29 to 1.78
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
29.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Emotional Well-Being Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
23.5 15.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.197
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
0.76 to 3.65
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
30.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Functional Well-Being Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
14.8 8.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.121
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
0.82 to 5.57
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
31.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline on the Anemia Subscale Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
27.2 15.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.075
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 2.00
Confidence Interval (2-Sided) 95%
0.93 to 4.30
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
32.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Fatigue Related Symptoms Subscale Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
27.2 18.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.222
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 1.58
Confidence Interval (2-Sided) 95%
0.76 to 3.29
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
33.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia Trial Outcome Index Subscale Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
19.8 12.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.249
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
0.71 to 3.83
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
34.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvment (CMI) From Baseline in the Functional Assessment of Cancer Therapy-Anemia-General Subscale Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
23.5 13.7
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.082
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 2.03
Confidence Interval (2-Sided) 95%
0.92 to 4.48
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
35.Secondary Outcome
Title Percentage of Participants With a Clinically Meaningful Improvement (CMI) From Baseline in the Functional Assessment of Cancer Therapy Anemia-Total Score Domain Within the FACT-An Instrument at Cycle 6
Hide Description A clinically meaningful improvement or deterioration was defined by domain specific thresholds of change from baseline. The FACT-An questionnaire is a 47-item, cancer specific questionnaire consisting of a core 27 items measuring 4 general domains physical well being, social/family, emotional well being and Functional Well-Being and an additional 20-item anemia questionnaire that measures fatigue and 7 non-fatigue items. The scales are formatted on 4 pages for self-administration using a 5-point Likert rating scale (0 = Not at all; 1 = A little bit; 2 = Somewhat; 3 = Quite a Bit and 4 = Very much). Also, general HRQoL measures the impact of fatigue and other anemia-related symptoms on patient functioning and is used to assess the effect of treatments in various areas, including MDS. The instrument and the fatigue and non-fatigue subscales are scored by summing points from all questions, then converting this sum to a 100 point scale; 0 = the poorest QOL and 100 = the highest QOL.
Time Frame Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
Health Related Quality of Life (HR-QoL) evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score at C1D1 and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
19.8 11.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.153
Comments [Not Specified]
Method Cochran-Mantel-Haenszel
Comments The p-value was calculated based on the CMH tests for comparing the odds of experiencing CMI between CC-486 versus placebo.
Method of Estimation Estimation Parameter Common Odds Ratio
Estimated Value 1.86
Confidence Interval (2-Sided) 95%
0.79 to 4.34
Estimation Comments [Not Specified]
Other Statistical Analysis The common odds ratio and the 95% confidence interval (CI) were calculated using CMH tests, stratified by randomization stratification factors, to compare the odds of experiencing clinically meaningful improvement between CC-486 and placebo.
36.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 2 Day 1 (C2D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 2.5 10.5
No Change 30.9 49.5
Worsened by 1 Level 25.9 23.2
Worsened by 2 Levels 23.5 6.3
Missing 17.3 10.5
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
37.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 3 Day 1 (C3D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 7.4 10.5
No Change 24.7 41.1
Worsened by 1 Level 16.0 18.9
Worsened by 2 Levels 23.5 13.7
Missing 28.4 15.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.046
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
38.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 4 Day 1 (C4D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 2.5 9.5
No Change 32.1 37.9
Worsened by 1 Level 16.0 14.7
Worsened by 2 Levels 14.8 6.3
Missing 34.6 31.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.134
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
39.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 5 Day 1 (C5D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 2.5 7.4
No Change 25.9 34.7
Worsened by 1 Level 13.6 12.6
Worsened by 2 Levels 8.6 5.3
Missing 49.4 40.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.324
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
40.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 6 Day 1 (C6 D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 1.2 4.2
No Change 25.9 27.4
Worsened by 1 Level 9.9 12.6
Worsened by 2 Levels 14.8 7.4
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.442
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
41.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to Cycle 7 Day 1 (C7D1)
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 1.2 1.1
No Change 25.9 21.1
Worsened by 1 Level 11.1 3.2
Worsened by 2 Levels 7.4 3.2
Missing 54.3 71.6
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.063
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
42.Secondary Outcome
Title Percentage of Participants With Change From Baseline in Responses to the Fact-Anemia Item GP-5
Hide Description The distribution (frequency and percentage) of the observed responses (i.e., "Not at all (0)," "A little bit (1)," "Somewhat (2)," "Quite a bit (3)," "Very much (4)," and missing) to Item GP-5 ("I am bothered by side effects of treatment" in the past seven days) of the FACT-An at each scheduled visit were summarized for each treatment group. The denominator for the percentage calculation per treatment group was based on the number of the FACT-An evaluable population at baseline. The distribution of change in responses (improved [i.e., change score from 1 to 4], no change [0], worsened by one level [-1], worsened by ≥2 levels [-2 to -4], and missing) from baseline at each post-baseline scheduled visit were summarized by treatment group.
Time Frame From Baseline to End of Treatment
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a non-missing FACT-An Trial Outcome Index (TOI) score baseline visit and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 2.5 6.3
No Change 14.8 25.3
Worsened by 1 Level 9.9 8.4
Worsened by 2 Levels 9.9 12.6
Missing 63.0 47.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.198
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
43.Secondary Outcome
Title Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level (EQ-5D-3L) Mobility Dimension Responses at Cycle 6
Hide Description The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.
Time Frame From Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a EQ-5D-3L health utility at baseline and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 8.6 8.4
No Change 35.8 33.7
Worsened 7.4 9.5
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.972
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
44.Secondary Outcome
Title Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level of Self-Care Dimension Responses at Cycle 6
Hide Description The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.
Time Frame From Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a EQ-5D-3L health utility at baseline and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 2.5 4.2
No Change 42.0 44.2
Worsened 7.4 3.2
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.601
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
45.Secondary Outcome
Title Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level Usual Activities Dimension Responses at Cycle 6
Hide Description TThe EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.
Time Frame From Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a EQ-5D-3L health utility at baseline and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 11.1 3.2
No Change 28.4 41.1
Worsened 12.3 7.4
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.070
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
46.Secondary Outcome
Title Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Pain/Discomfort Dimension Responses at Cycle 6
Hide Description The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.
Time Frame From Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a EQ-5D-3L health utility at baseline and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 13.6 8.4
No Change 33.3 32.6
Worsened 4.9 10.5
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.436
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
47.Secondary Outcome
Title Percentage of Participants With Improved, Worsened, or No Change in the European Quality of Life-Five Dimension-Three Level in the Anxiety/Depression Dimension Responses at Cycle 6
Hide Description The EQ-5D-3L is a generic, self-administered questionnaire that consists of 5 dimensions: mobility, self-care, pain, usual activities, and anxiety/depression. Each dimension has 3 levels of severity corresponding to no problems, some problems, and extreme problems. It also includes a Visual Analog Scale that recorded the respondent's self-rated health on a vertical, 0-100 scale, where 100 = Best imaginable health state and 0 = Worst imaginable health state. Distribution of the observed responses (i.e., no problems, moderate problems, severe problems, and missing) of the 5 dimensions at each visit was summarized per arm. The denominator for the percentage calculation per group was based on the number of the EQ-5D-3L evaluable population at baseline. The distribution of change in responses (i.e., improved [by ≥1 level], no change, worsened [by ≥1 level], and missing) from baseline are reported.
Time Frame From Baseline to Cycle 6 Day 1
Hide Outcome Measure Data
Hide Analysis Population Description
The HRQoL evaluable population was defined as participants with a EQ-5D-3L health utility at baseline and at least one post-baseline assessment visit.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 81 95
Measure Type: Number
Unit of Measure: Percentage of Participants
Improved 4.9 7.4
No Change 35.8 37.9
Worsened 11.1 6.3
Missing 48.1 48.4
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Oral Azacitidine and Best Supportive Care, Placebo Plus Best Supportive Care
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.683
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
48.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Number of Participants Who Were Hospitalized During the Treatment Period
Hide Description The number of reasons for hospitalizations and hospital admissions during the treatment period were monitored and include those associated with: AEs, protocol-driven procedures, transfusions, non-protocol procedures, elective procedures or those associated with social, practical or technical reasons in the absence of AEs. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Time Frame From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all randomized participants who received at least one dose of study drug.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Count of Participants
Unit of Measure: Participants
Adverse Events
79
  73.8%
65
  59.6%
Protocol Driven Procedures
2
   1.9%
7
   6.4%
Non-Protocol Driven Procedures
9
   8.4%
19
  17.4%
Transfusion
32
  29.9%
33
  30.3%
Procedure Planned Prior to Signing Consent
0
   0.0%
4
   3.7%
Elective Procedures
4
   3.7%
10
   9.2%
Social, Technical or Practical Reason except AEs
4
   3.7%
6
   5.5%
49.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Due to Any Reason During the Treatment Period
Hide Description The total number of days hospitalized due to any reason during the treatment period was monitored. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Time Frame From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all randomized participants who received at least one dose of study drug.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Unit of Measure: Days
3513 2688
50.Secondary Outcome
Title Healthcare Resource Utilization (HRU): Total Number of Days Hospitalized Per Total Patient-Years
Hide Description The number of days hospitalized per total patient years. HRU was defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient.
Time Frame From date of randomization up to 28 days after the last dose of study drug; up to data cut off date of 25 January 2019; median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
Hide Outcome Measure Data
Hide Analysis Population Description
The safety population includes all randomized participants who received at least one dose of study drug.
Arm/Group Title Oral Azacitidine and Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description:
Participants received 300 mg oral azacitidine tablets daily on days 1 to 21 of each 28-day treatment cycle and BSC included and was not limited to pRBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections.
Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
Overall Number of Participants Analyzed 107 109
Measure Type: Number
Unit of Measure: Days Per Total Patient Years
41.44 40.53
Time Frame Treatment Emergent AEs were monitored from randomization date up to 28 days after the last dose of IP;; up to data cut-off date of 25 Jan 2019; up to 69 months.
Adverse Event Reporting Description Median duration of treatment to oral azacitaidine was 5.29 months and 5.36 months for placebo
 
Arm/Group Title Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Hide Arm/Group Description Participants received 300 mg oral azacitidine tablets daily (QD) on days 1 to 21 of each 28-day treatment cycle and best supportive care (BSC) which included and was not limited to packed RBC (packed red blood cell [pRBC] and whole blood), platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and granulocyte colony stimulating factors (G-CSF) for participants who experienced neutropenic fever/infections. Participants received identically matching placebo tablets QD on days 1 to 21 of each 28-day treatment cycle and BSC which included but was not limited to, pRBC and whole blood, platelet transfusions (single donor or pooled donor), antibiotic, antiviral and/or antifungal therapy, nutritional support, and G-CSF for participants who experienced neutropenic fever/infections.
All-Cause Mortality
Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   69/107 (64.49%)   71/109 (65.14%) 
Hide Serious Adverse Events
Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   79/107 (73.83%)   69/109 (63.30%) 
Blood and lymphatic system disorders     
Anaemia  1  5/107 (4.67%)  5/109 (4.59%) 
Bone marrow failure  1  2/107 (1.87%)  0/109 (0.00%) 
Febrile neutropenia  1  29/107 (27.10%)  9/109 (8.26%) 
Haemolytic anaemia  1  1/107 (0.93%)  0/109 (0.00%) 
Haemorrhagic anaemia  1  1/107 (0.93%)  0/109 (0.00%) 
Neutropenia  1  2/107 (1.87%)  1/109 (0.92%) 
Pancytopenia  1  1/107 (0.93%)  0/109 (0.00%) 
Thrombocytopenia  1  4/107 (3.74%)  1/109 (0.92%) 
Cardiac disorders     
Acute myocardial infarction  1  1/107 (0.93%)  0/109 (0.00%) 
Angina pectoris  1  0/107 (0.00%)  1/109 (0.92%) 
Angina unstable  1  1/107 (0.93%)  0/109 (0.00%) 
Atrial fibrillation  1  1/107 (0.93%)  2/109 (1.83%) 
Atrioventricular block first degree  1  0/107 (0.00%)  1/109 (0.92%) 
Cardiac arrest  1  0/107 (0.00%)  1/109 (0.92%) 
Cardiac failure  1  2/107 (1.87%)  2/109 (1.83%) 
Cardiac failure congestive  1  3/107 (2.80%)  0/109 (0.00%) 
Cardio-respiratory arrest  1  0/107 (0.00%)  1/109 (0.92%) 
Cardiogenic shock  1  1/107 (0.93%)  0/109 (0.00%) 
Long QT syndrome  1  0/107 (0.00%)  1/109 (0.92%) 
Myocardial infarction  1  1/107 (0.93%)  2/109 (1.83%) 
Tachyarrhythmia  1  2/107 (1.87%)  0/109 (0.00%) 
Ventricular tachycardia  1  0/107 (0.00%)  1/109 (0.92%) 
Gastrointestinal disorders     
Abdominal pain  1  3/107 (2.80%)  0/109 (0.00%) 
Abdominal pain upper  1  1/107 (0.93%)  0/109 (0.00%) 
Colitis  1  0/107 (0.00%)  1/109 (0.92%) 
Constipation  1  1/107 (0.93%)  0/109 (0.00%) 
Diarrhoea  1  3/107 (2.80%)  0/109 (0.00%) 
Gastritis  1  1/107 (0.93%)  0/109 (0.00%) 
Gastrointestinal haemorrhage  1  1/107 (0.93%)  2/109 (1.83%) 
Haemorrhoidal haemorrhage  1  0/107 (0.00%)  1/109 (0.92%) 
Intestinal obstruction  1  1/107 (0.93%)  0/109 (0.00%) 
Intestinal perforation  1  1/107 (0.93%)  0/109 (0.00%) 
Intra-abdominal haemorrhage  1  1/107 (0.93%)  0/109 (0.00%) 
Melaena  1  0/107 (0.00%)  2/109 (1.83%) 
Nausea  1  2/107 (1.87%)  0/109 (0.00%) 
Neutropenic colitis  1  1/107 (0.93%)  0/109 (0.00%) 
Oesophageal achalasia  1  1/107 (0.93%)  0/109 (0.00%) 
Oral mucosal blistering  1  1/107 (0.93%)  0/109 (0.00%) 
Rectal haemorrhage  1  1/107 (0.93%)  1/109 (0.92%) 
Upper gastrointestinal haemorrhage  1  0/107 (0.00%)  1/109 (0.92%) 
Vomiting  1  1/107 (0.93%)  0/109 (0.00%) 
General disorders     
Fatigue  1  0/107 (0.00%)  1/109 (0.92%) 
Gait disturbance  1  1/107 (0.93%)  0/109 (0.00%) 
General physical health deterioration  1  3/107 (2.80%)  1/109 (0.92%) 
Hypothermia  1  1/107 (0.93%)  0/109 (0.00%) 
Multiple organ dysfunction syndrome  1  2/107 (1.87%)  0/109 (0.00%) 
Pyrexia  1  8/107 (7.48%)  4/109 (3.67%) 
Sudden death  1  0/107 (0.00%)  1/109 (0.92%) 
Hepatobiliary disorders     
Biliary colic  1  0/107 (0.00%)  1/109 (0.92%) 
Cholecystitis  1  2/107 (1.87%)  1/109 (0.92%) 
Hyperbilirubinaemia  1  2/107 (1.87%)  0/109 (0.00%) 
Infections and infestations     
Abscess limb  1  1/107 (0.93%)  0/109 (0.00%) 
Arteriovenous fistula site infection  1  1/107 (0.93%)  0/109 (0.00%) 
Atypical pneumonia  1  2/107 (1.87%)  0/109 (0.00%) 
Bacteraemia  1  0/107 (0.00%)  2/109 (1.83%) 
Bronchitis  1  0/107 (0.00%)  1/109 (0.92%) 
Bronchopulmonary aspergillosis  1  2/107 (1.87%)  0/109 (0.00%) 
Cellulitis  1  1/107 (0.93%)  0/109 (0.00%) 
Clostridium difficile colitis  1  0/107 (0.00%)  1/109 (0.92%) 
Corona virus infection  1  1/107 (0.93%)  0/109 (0.00%) 
Cystitis escherichia  1  0/107 (0.00%)  1/109 (0.92%) 
Device related infection  1  1/107 (0.93%)  0/109 (0.00%) 
Diverticulitis  1  0/107 (0.00%)  1/109 (0.92%) 
Epididymitis  1  1/107 (0.93%)  0/109 (0.00%) 
Escherichia sepsis  1  1/107 (0.93%)  0/109 (0.00%) 
Febrile infection  1  1/107 (0.93%)  1/109 (0.92%) 
Gastroenteritis  1  1/107 (0.93%)  0/109 (0.00%) 
Gastroenteritis clostridial  1  0/107 (0.00%)  1/109 (0.92%) 
Groin abscess  1  1/107 (0.93%)  0/109 (0.00%) 
Haemophilus infection  1  0/107 (0.00%)  1/109 (0.92%) 
Infection  1  0/107 (0.00%)  1/109 (0.92%) 
Influenza  1  1/107 (0.93%)  0/109 (0.00%) 
Klebsiella infection  1  1/107 (0.93%)  0/109 (0.00%) 
Klebsiella sepsis  1  1/107 (0.93%)  0/109 (0.00%) 
Lower respiratory tract infection  1  1/107 (0.93%)  4/109 (3.67%) 
Lung infection  1  3/107 (2.80%)  0/109 (0.00%) 
Lymph gland infection  1  0/107 (0.00%)  1/109 (0.92%) 
Meningitis  1  1/107 (0.93%)  0/109 (0.00%) 
Meningitis bacterial  1  1/107 (0.93%)  0/109 (0.00%) 
Myringitis  1  1/107 (0.93%)  0/109 (0.00%) 
Neutropenic sepsis  1  5/107 (4.67%)  1/109 (0.92%) 
Pharyngeal abscess  1  0/107 (0.00%)  1/109 (0.92%) 
Pharyngitis  1  0/107 (0.00%)  2/109 (1.83%) 
Pneumonia  1  10/107 (9.35%)  12/109 (11.01%) 
Pneumonia fungal  1  1/107 (0.93%)  0/109 (0.00%) 
Pneumonia pneumococcal  1  1/107 (0.93%)  0/109 (0.00%) 
Prostatic abscess  1  0/107 (0.00%)  1/109 (0.92%) 
Pseudomonal sepsis  1  1/107 (0.93%)  0/109 (0.00%) 
Pulmonary mycosis  1  1/107 (0.93%)  0/109 (0.00%) 
Respiratory tract infection  1  1/107 (0.93%)  1/109 (0.92%) 
Respiratory tract infection bacterial  1  0/107 (0.00%)  1/109 (0.92%) 
Sepsis  1  8/107 (7.48%)  3/109 (2.75%) 
Septic shock  1  6/107 (5.61%)  3/109 (2.75%) 
Skin infection  1  1/107 (0.93%)  0/109 (0.00%) 
Staphylococcal infection  1  1/107 (0.93%)  1/109 (0.92%) 
Staphylococcal sepsis  1  0/107 (0.00%)  1/109 (0.92%) 
Tooth abscess  1  0/107 (0.00%)  1/109 (0.92%) 
Upper respiratory tract infection  1  3/107 (2.80%)  1/109 (0.92%) 
Urinary tract infection  1  2/107 (1.87%)  1/109 (0.92%) 
Urinary tract infection bacterial  1  1/107 (0.93%)  1/109 (0.92%) 
Viral sepsis  1  1/107 (0.93%)  0/109 (0.00%) 
Injury, poisoning and procedural complications     
Arteriovenous fistula site haemorrhage  1  0/107 (0.00%)  1/109 (0.92%) 
Cystitis radiation  1  0/107 (0.00%)  1/109 (0.92%) 
Fall  1  4/107 (3.74%)  0/109 (0.00%) 
Febrile nonhaemolytic transfusion reaction  1  1/107 (0.93%)  0/109 (0.00%) 
Head injury  1  1/107 (0.93%)  0/109 (0.00%) 
Hip fracture  1  1/107 (0.93%)  0/109 (0.00%) 
Periorbital haematoma  1  1/107 (0.93%)  0/109 (0.00%) 
Subdural haematoma  1  2/107 (1.87%)  0/109 (0.00%) 
Subdural haemorrhage  1  1/107 (0.93%)  0/109 (0.00%) 
Transfusion reaction  1  0/107 (0.00%)  1/109 (0.92%) 
Upper limb fracture  1  1/107 (0.93%)  0/109 (0.00%) 
Investigations     
Gamma-glutamyltransferase increased  1  0/107 (0.00%)  1/109 (0.92%) 
Weight decreased  1  1/107 (0.93%)  0/109 (0.00%) 
Metabolism and nutrition disorders     
Dehydration  1  1/107 (0.93%)  1/109 (0.92%) 
Diabetes mellitus  1  0/107 (0.00%)  1/109 (0.92%) 
Diabetes mellitus inadequate control  1  1/107 (0.93%)  0/109 (0.00%) 
Diabetic metabolic decompensation  1  1/107 (0.93%)  0/109 (0.00%) 
Hyperkalaemia  1  1/107 (0.93%)  0/109 (0.00%) 
Hypoglycaemia  1  1/107 (0.93%)  0/109 (0.00%) 
Hyponatraemia  1  0/107 (0.00%)  1/109 (0.92%) 
Musculoskeletal and connective tissue disorders     
Back pain  1  1/107 (0.93%)  0/109 (0.00%) 
Muscular weakness  1  1/107 (0.93%)  0/109 (0.00%) 
Polychondritis  1  1/107 (0.93%)  0/109 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute myeloid leukaemia  1  1/107 (0.93%)  2/109 (1.83%) 
Basal cell carcinoma  1  0/107 (0.00%)  1/109 (0.92%) 
Bone neoplasm  1  1/107 (0.93%)  0/109 (0.00%) 
Bowen's disease  1  1/107 (0.93%)  0/109 (0.00%) 
Carcinoma in situ of skin  1  0/107 (0.00%)  1/109 (0.92%) 
Central nervous system leukaemia  1  0/107 (0.00%)  1/109 (0.92%) 
Chronic myelomonocytic leukaemia  1  0/107 (0.00%)  1/109 (0.92%) 
Colon adenoma  1  1/107 (0.93%)  0/109 (0.00%) 
Colon cancer  1  0/107 (0.00%)  1/109 (0.92%) 
Malignant neoplasm of unknown primary site  1  0/107 (0.00%)  1/109 (0.92%) 
Mantle cell lymphoma recurrent  1  1/107 (0.93%)  0/109 (0.00%) 
Myelodysplastic syndrome  1  0/107 (0.00%)  3/109 (2.75%) 
Refractory anaemia with an excess of blasts  1  0/107 (0.00%)  1/109 (0.92%) 
Spinal cord neoplasm  1  1/107 (0.93%)  0/109 (0.00%) 
Squamous cell carcinoma of skin  1  0/107 (0.00%)  1/109 (0.92%) 
Transformation to acute myeloid leukaemia  1  0/107 (0.00%)  6/109 (5.50%) 
Nervous system disorders     
Central nervous system lesion  1  1/107 (0.93%)  0/109 (0.00%) 
Cerebral haemorrhage  1  0/107 (0.00%)  1/109 (0.92%) 
Epilepsy  1  1/107 (0.93%)  0/109 (0.00%) 
Generalised tonic-clonic seizure  1  1/107 (0.93%)  0/109 (0.00%) 
Guillain-Barre syndrome  1  0/107 (0.00%)  1/109 (0.92%) 
Haemorrhage intracranial  1  2/107 (1.87%)  0/109 (0.00%) 
IIIrd nerve paresis  1  0/107 (0.00%)  1/109 (0.92%) 
Lethargy  1  1/107 (0.93%)  0/109 (0.00%) 
Presyncope  1  0/107 (0.00%)  1/109 (0.92%) 
Sciatica  1  0/107 (0.00%)  1/109 (0.92%) 
Status epilepticus  1  1/107 (0.93%)  0/109 (0.00%) 
Syncope  1  1/107 (0.93%)  0/109 (0.00%) 
Transient ischaemic attack  1  1/107 (0.93%)  1/109 (0.92%) 
Psychiatric disorders     
Bipolar disorder  1  0/107 (0.00%)  1/109 (0.92%) 
Confusional state  1  0/107 (0.00%)  2/109 (1.83%) 
Renal and urinary disorders     
Acute kidney injury  1  2/107 (1.87%)  3/109 (2.75%) 
Chronic kidney disease  1  1/107 (0.93%)  0/109 (0.00%) 
Haematuria  1  0/107 (0.00%)  1/109 (0.92%) 
Prerenal failure  1  1/107 (0.93%)  0/109 (0.00%) 
Renal colic  1  1/107 (0.93%)  0/109 (0.00%) 
Renal failure  1  2/107 (1.87%)  0/109 (0.00%) 
Urinary retention  1  1/107 (0.93%)  1/109 (0.92%) 
Urinary tract obstruction  1  0/107 (0.00%)  1/109 (0.92%) 
Reproductive system and breast disorders     
Prostatitis  1  1/107 (0.93%)  0/109 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/107 (0.93%)  0/109 (0.00%) 
Epistaxis  1  2/107 (1.87%)  1/109 (0.92%) 
Haemoptysis  1  0/107 (0.00%)  1/109 (0.92%) 
Laryngeal oedema  1  0/107 (0.00%)  1/109 (0.92%) 
Pleural effusion  1  1/107 (0.93%)  1/109 (0.92%) 
Pleurisy  1  1/107 (0.93%)  0/109 (0.00%) 
Pleuritic pain  1  0/107 (0.00%)  1/109 (0.92%) 
Pneumonia aspiration  1  1/107 (0.93%)  0/109 (0.00%) 
Pulmonary embolism  1  1/107 (0.93%)  0/109 (0.00%) 
Pulmonary oedema  1  0/107 (0.00%)  2/109 (1.83%) 
Respiratory failure  1  1/107 (0.93%)  0/109 (0.00%) 
Skin and subcutaneous tissue disorders     
Hypersensitivity vasculitis  1  1/107 (0.93%)  0/109 (0.00%) 
Rash  1  1/107 (0.93%)  0/109 (0.00%) 
Rash generalised  1  1/107 (0.93%)  0/109 (0.00%) 
Vascular disorders     
Arteritis  1  0/107 (0.00%)  1/109 (0.92%) 
Haematoma  1  1/107 (0.93%)  0/109 (0.00%) 
Polyarteritis nodosa  1  0/107 (0.00%)  1/109 (0.92%) 
Shock haemorrhagic  1  1/107 (0.93%)  0/109 (0.00%) 
1
Term from vocabulary, 21.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
Affected / at Risk (%) Affected / at Risk (%)
Total   107/107 (100.00%)   104/109 (95.41%) 
Blood and lymphatic system disorders     
Anaemia  1  19/107 (17.76%)  17/109 (15.60%) 
Leukopenia  1  10/107 (9.35%)  0/109 (0.00%) 
Neutropenia  1  52/107 (48.60%)  15/109 (13.76%) 
Thrombocytopenia  1  29/107 (27.10%)  18/109 (16.51%) 
Gastrointestinal disorders     
Abdominal pain  1  14/107 (13.08%)  14/109 (12.84%) 
Constipation  1  50/107 (46.73%)  24/109 (22.02%) 
Diarrhoea  1  73/107 (68.22%)  25/109 (22.94%) 
Gastrooesophageal reflux disease  1  6/107 (5.61%)  0/109 (0.00%) 
Gingival bleeding  1  7/107 (6.54%)  0/109 (0.00%) 
Haemorrhoids  1  0/107 (0.00%)  6/109 (5.50%) 
Mouth haemorrhage  1  10/107 (9.35%)  7/109 (6.42%) 
Nausea  1  81/107 (75.70%)  25/109 (22.94%) 
Rectal haemorrhage  1  0/107 (0.00%)  8/109 (7.34%) 
Vomiting  1  67/107 (62.62%)  10/109 (9.17%) 
General disorders     
Asthenia  1  25/107 (23.36%)  20/109 (18.35%) 
Fatigue  1  23/107 (21.50%)  22/109 (20.18%) 
Oedema peripheral  1  29/107 (27.10%)  17/109 (15.60%) 
Pyrexia  1  30/107 (28.04%)  15/109 (13.76%) 
Infections and infestations     
Cellulitis  1  6/107 (5.61%)  0/109 (0.00%) 
Oral herpes  1  6/107 (5.61%)  0/109 (0.00%) 
Pneumonia  1  7/107 (6.54%)  0/109 (0.00%) 
Upper respiratory tract infection  1  7/107 (6.54%)  0/109 (0.00%) 
Urinary tract infection  1  12/107 (11.21%)  0/109 (0.00%) 
Injury, poisoning and procedural complications     
Contusion  1  15/107 (14.02%)  0/109 (0.00%) 
Investigations     
Alanine aminotransferase increased  1  9/107 (8.41%)  6/109 (5.50%) 
Serum ferritin increased  1  6/107 (5.61%)  0/109 (0.00%) 
Weight decreased  1  10/107 (9.35%)  0/109 (0.00%) 
Metabolism and nutrition disorders     
Decreased appetite  1  27/107 (25.23%)  10/109 (9.17%) 
Hyperglycaemia  1  6/107 (5.61%)  0/109 (0.00%) 
Hypokalaemia  1  12/107 (11.21%)  10/109 (9.17%) 
Hypomagnesaemia  1  10/107 (9.35%)  0/109 (0.00%) 
Iron overload  1  6/107 (5.61%)  11/109 (10.09%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/107 (8.41%)  11/109 (10.09%) 
Back pain  1  13/107 (12.15%)  13/109 (11.93%) 
Pain in extremity  1  7/107 (6.54%)  0/109 (0.00%) 
Nervous system disorders     
Dizziness  1