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    Clinical Trial Results:
    A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO COMPARE EFFICACY AND SAFETY OF ORAL AZACITIDINE PLUS BEST SUPPORTIVE CARE VERSUS BEST SUPPORTIVE CARE AS MAINTENANCE THERAPY IN SUBJECTS WITH ACUTE MYELOID LEUKEMIA IN COMPLETE REMISSION

    Summary
    EudraCT number
    		 2012-003457-28
    Trial protocol
    		 BE   CZ   PT   LT   IT   ES   FI   DE   AT   PL   IE   GB   FR  
    Global end of trial date
    18 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jul 2025
    First version publication date
    04 Jul 2025
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CC-486-AML-001
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Bristol-Myers Squibb
    Sponsor organisation address
    Chaussée de la Hulpe 185, Brussels, Belgium, 1170
    Public contact
    Global Submission Management, Clinical Trials, Bristol-Myers Squibb International Corporation, mg-gsm-ct@bms.com
    Scientific contact
    Bristol-Myers Squibb Study Director, Bristol-Myers Squibb, mg-gsm-ct@bms.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Aug 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate whether maintenance therapy with oral azacitidine improves OS compared with placebo in subjects with AML, age ≥ 55 years, who have achieved first CR or CRi after induction with intensive chemotherapy with or without consolidation chemotherapy.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonization Good Clinical Practice Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Apr 2013
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Italy: 75
    Country: Number of subjects enrolled
    Spain: 38
    Country: Number of subjects enrolled
    United Kingdom: 35
    Country: Number of subjects enrolled
    Germany: 32
    Country: Number of subjects enrolled
    Russian Federation: 19
    Country: Number of subjects enrolled
    Türkiye: 18
    Country: Number of subjects enrolled
    Portugal: 15
    Country: Number of subjects enrolled
    Austria: 14
    Country: Number of subjects enrolled
    Poland: 14
    Country: Number of subjects enrolled
    France: 13
    Country: Number of subjects enrolled
    Belgium: 11
    Country: Number of subjects enrolled
    Czechia: 10
    Country: Number of subjects enrolled
    Finland: 9
    Country: Number of subjects enrolled
    Israel: 9
    Country: Number of subjects enrolled
    Ireland: 1
    Country: Number of subjects enrolled
    Lithuania: 1
    Country: Number of subjects enrolled
    United States: 60
    Country: Number of subjects enrolled
    Canada: 17
    Country: Number of subjects enrolled
    Mexico: 2
    Country: Number of subjects enrolled
    Australia: 49
    Country: Number of subjects enrolled
    Korea, Republic of: 15
    Country: Number of subjects enrolled
    Taiwan: 8
    Country: Number of subjects enrolled
    Brazil: 7
    Worldwide total number of subjects
    472
    EEA total number of subjects
    233
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    134
    From 65 to 84 years
    337
    85 years and over
    1

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 472 Participants Randomized, 469 participants treated

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Oral Azacitidine Plus Best Supportive Care
    Arm description
    		 Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.
    Arm type
    		 Experimental

    Investigational medicinal product name
    azacitidine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    150 and/or 200mg

    Arm title
    		 Placebo Plus Best Supportive Care
    Arm description
    		 Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.
    Arm type
    		 Placebo

    Investigational medicinal product name
    placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    placebo

    Number of subjects in period 1
    		Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Started
    238
    234
    Received Treatment
    236
    233
    Completed
    0
    0
    Not completed
    238
    234
         Adverse event, serious fatal
    2
    2
         Physician decision
    7
    -
         Disease Relapse
    151
    181
         Withdrew Consent
    19
    13
         Adverse event, non-fatal
    31
    11
         Other Reasons
    28
    27

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Oral Azacitidine Plus Best Supportive Care
    Reporting group description
    		 Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.

    Reporting group title
    Placebo Plus Best Supportive Care
    Reporting group description
    		 Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.

    Reporting group values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care Total
    Number of subjects
    		 238 234 472
    Age Categorical
    Units: Participants
        18 to 64 Years
    		 66 68 134
        65 to 84 Years
    		 171 166 337
        ≥ 85 years
    		 1 0 1
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 67.9 ( 5.72 ) 68.0 ( 5.62 ) -
    Sex: Female, Male
    Units: Participants
        Female
    		 120 107 227
        Male
    		 118 127 245
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 20 14 34
        Not Hispanic or Latino
    		 196 202 398
        Unknown or Not Reported
    		 22 18 40
    Race/Ethnicity, Customized
    Units: Subjects
        White
    		 216 197 413
        Black or African-American
    		 2 6 8
        Asian
    		 6 20 26
        Other
    		 12 11 23
        Missing
    		 2 0 2
    Initial Acute Myeloid Leukemia (AML) Classification
    AML is classified using the WHO classification system based upon a combination of morphology, immunophenotype, genetics, and clinical features. There are several broad groups and include: 1. AML with genetic abnormalities; 2. AML with multilineage dysplasia 3. AML related to previous chemotherapy or radiation 4. Unspecified AML - do not fall into the above groups
    Units: Subjects
        AML with Recurrent Genetic Abnormalities
    		 39 46 85
        AML with Myelodysplasia - Related Changes
    		 49 42 91
        Therapy-related Myeloid Neoplasms
    		 2 0 2
        AML not Otherwise Specified
    		 148 145 293
        Missing
    		 0 1 1
    Type of Acute Myeloid Leukemia (AML)
    Primary AML is a cancer that originates in the blood and bone marrow. AML affects a group of white blood cells called myeloid cells, which normally develop into the various types of mature blood cells, such as red blood cells, white blood cells and platelets. Secondary acute myeloid leukemia (s-AML) refers to a leukemic process: (1) evolving from prior myelodysplasia (MDS), myeloproliferative disorder (MPN), or aplastic anemia (AA) with or without treatment or (2) as a product of previous exposure to a proven leukemogenic chemotherapeutic agent (therapy-related AML [t-AML]).
    Units: Subjects
        Primary (de novo)
    		 213 216 429
        Secondary
    		 25 18 43
    Cytogenetic Risk Category at Diagnosis
    Cytogenetic Risk - Intermediate -I is of a normal karyotype; Poor Risk - includes complex karyotypes having 3 or more cytogenetic abnormalities.
    Units: Subjects
        Intermediate
    		 203 203 406
        Poor
    		 35 31 66
    Eastern Cooperative Oncology Group (ECOG) Performance Status
    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.
    Units: Subjects
        Grade 0
    		 116 111 227
        Grade 1
    		 101 106 207
        Grade 2
    		 21 15 36
        Grade 3
    		 0 2 2

    End points

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    End points reporting groups
    Reporting group title
    Oral Azacitidine Plus Best Supportive Care
    Reporting group description
    		 Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.

    Reporting group title
    Placebo Plus Best Supportive Care
    Reporting group description
    		 Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.

    Primary: Kaplan-Meier (K-M) Estimate for Overall Survival (OS)

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    End point title
    		 Kaplan-Meier (K-M) Estimate for Overall Survival (OS)
    End point description
    Overall survival was defined as time from randomization to death from any cause; participants surviving at the end of the follow-up period, or who withdraw consent, or who were lost to follow up were censored at the date last known alive.
    End point type
    Primary
    End point timeframe
    Day 1 (randomization) up to data cut off date of 15 July 2019; median follow-up for OS estimated by the reverse K-M method was 41.2 months for all participants.
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    238
    234
    Units: Months
        median (confidence interval 95%)
    24.7 (18.7 to 30.5)
    14.8 (11.7 to 17.6)
    Statistical analysis title
    		 Statistical Analysis for OS
    Comparison groups
    Oral Azacitidine Plus Best Supportive Care v Placebo Plus Best Supportive Care
    Number of subjects included in analysis
    472
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0009 [1]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.86
    Notes
    [1] - The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not.

    Secondary: Kaplan-Meier Estimate of Relapse Free Survival (RFS)

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    End point title
    		 Kaplan-Meier Estimate of Relapse Free Survival (RFS)
    End point description
    RFS was defined as the time from the date of randomization to the date of documented relapse or death from any cause, whichever occurred first. Participants who were still alive without documented relapse, or who were lost to follow-up or withdrew consent without documented relapse, were censored at the date of their last bone marrow assessment, prior to receiving any other therapy for AML. Documented relapse was defined as the earliest date of the following: • ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or • appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or • at least 2 peripheral blasts ≥ 5% within 30 days.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    238
    234
    Units: Months
        median (confidence interval 95%)
    10.2 (7.9 to 12.9)
    4.8 (4.6 to 6.4)
    Statistical analysis title
    		 Statistical Analysis for RFS
    Comparison groups
    Oral Azacitidine Plus Best Supportive Care v Placebo Plus Best Supportive Care
    Number of subjects included in analysis
    472
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001 [2]
    Method
    		 Logrank
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.65
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.52
         upper limit
    		 0.8
    Notes
    [2] - The p-value is 2-sided from a log-rank test stratified by age, cytogenetic risk category, and received consolidation therapy or not.

    Secondary: Kaplan-Meier Estimate of Time to Relapse

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    End point title
    		 Kaplan-Meier Estimate of Time to Relapse
    End point description
    Time to relapse was defined as the interval (in months) from the date of randomization to the date of documented relapse. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from complete remission (CR)/ complete remission with incomplete blood count recovery (CRi). Documented relapse was defined as, the earliest date of the following: • ≥ 5% bone marrow blasts (myeloblasts) from Central Pathology report, or • appearance of > 0% blasts in the peripheral blood with a later bone marrow confirmation (bone marrow blast [myeloblasts] ≥ 5%) within 100 days, or • at least 2 peripheral blasts ≥ 5% within 30 days.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    238
    234
    Units: months
        median (confidence interval 95%)
    10.2 (8.3 to 13.4)
    4.9 (4.6 to 6.4)
    No statistical analyses for this end point

    Secondary: Kaplan-Meier Estimates of Time to Discontinuation from Treatment

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    End point title
    		 Kaplan-Meier Estimates of Time to Discontinuation from Treatment
    End point description
    Time to discontinuation from treatment was assessed and defined as the interval from the date of randomization to the date of discontinuation from study drug. Participants who were receiving treatment at the time of study closure were censored at the date of last visit. Estimates of relapse rate were based on the cumulative incidence function from a competing risk analysis with death as a competing risk for relapse from CR/ CRi.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    238
    234
    Units: months
        median (confidence interval 95%)
    14.6 (11.3 to 20.1)
    6.9 (5.3 to 7.9)
    No statistical analyses for this end point

    Secondary: Number of Participants with Treatment Emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants with Treatment Emergent Adverse Events (TEAEs)
    End point description
    TEAEs include AEs that started between first dose date and 28 days after the last dose of study drug. A serious adverse event (SAE) is: • Death • Life-threatening event • Inpatient hospitalization or prolongation of existing hospitalization • Persistent or significant disability or incapacity • Congenital anomaly or birth defect • Other important medical event The severity of AEs were assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0: Grade 1 (Mild): asymptomatic/mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 (Moderate): minimal, local or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care Grade 4: Life-threatening; urgent intervention indicated. Grade 5: Death due to AE.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    236
    233
    Units: Participants
        ≥ 1 TEAE
    235
    233
        ≥ 1 TEAE Related to Study Treatment
    213
    121
        ≥ 1 Serious TEAE
    110
    109
        ≥ 1 Treatment Related Serious TEAE
    22
    5
        ≥ 1 Grade 3/4 TEAE
    207
    201
        ≥ 1 Treatment Related Grade 3/4 TEAE
    113
    55
        ≥ 1 TEAE Leading to Death
    15
    11
        ≥ 1 TEAE Leading to Dose Reduction (Red)
    37
    6
        ≥ 1 TEAE Leading to Dose Interruption
    107
    43
        ≥ 1 TEAE Leading to Dose Red and Interruption
    25
    3
        ≥ 1 TEAE Leading to Study Drug Discontinuation
    155
    170
    No statistical analyses for this end point

    Secondary: Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score from Baseline

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    End point title
    		 Mean Change in the Functional Assessment of Chronic Illness Therapy (FACIT-Fatigue Scale V 4.0) Score from Baseline
    End point description
    The functional assessment of chronic illness therapy (FACIT-Fatigue Scale V 4.0) is a subscale of the FACIT-F and has been validated in the oncology setting. The FACIT-Fatigue Scale is a short, 13-item, self-administered tool that measures the level of fatigue in an individual during usually daily activities over the past week. The level of fatigue is measured on a 5-point Likert scale (0 = not at all; 4 = very much. The scores range from 0 to 52, with higher scores indicating less fatigue. If there were missing items, but the participant answered at least 50% of the items, then subscores were prorated.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    165
    150
    Units: units on a scale
        arithmetic mean (standard deviation)
    -3.7 ( 10.92 )
    -2.5 ( 9.93 )
    No statistical analyses for this end point

    Secondary: Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score from Baseline

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    End point title
    		 Mean Change in the European Quality of Life-Five Dimensions-Three Levels (EQ-5D-3L) Score from Baseline
    End point description
    The EQ-5D-3L is a self-administered questionnaire consisting of 5 questions, pertaining to specific health dimensions (ie, mobility, self-care, pain, usual activities, and anxiety/depression) and a health status scale. Each question has 3 levels of severity, corresponding to no problems, moderate problems and severe problems. Canadian population sample weights were used to derive health utility scores. A higher utility score represents a better health state. A clinically meaningful improvement or worsening was defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline, respectively, for the EQ-5D-3L Health Utility Index. The instrument is scored using the United Kingdom (UK) index ranges from -0.594 to 1, where 0 equates to death and 1 equates to full health; -0.594 is considered 'worse than death’.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    164
    150
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -0.0416 ( 0.15467 )
    -0.0152 ( 0.14799 )
    No statistical analyses for this end point

    Secondary: Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale

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    End point title
    		 Time to Definitive Clinically Meaningful Deterioration for ≥ 2 Consecutive Visits as Measured Using the EQ-5D HRQoL Scale
    End point description
    Clinically meaningful deterioration is defined as a decrease of at least 0.10 points from baseline for at least 2 consecutive visits on the EQ-5D Health Utility Index. The EQ-5D-3L is a self-administered questionnaire with 5 questions covering health dimensions like mobility, self-care, pain, usual activities, and anxiety/depression, plus a health status scale. Each question has 3 severity levels: no problems, moderate problems, and severe problems. Canadian population sample weights derive health utility scores, where higher scores indicate better health. Clinically meaningful improvement or worsening is defined as at least 0.08 points of improvement or 0.10 points of worsening from baseline. The EQ-5D-3L uses the UK index, ranging from -0.594 to 1, where 0 equates to death and 1 to full health; -0.594 is considered 'worse than death'. here "99999" means NA
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 15 July 2019; approximately 74 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    225
    217
    Units: Weeks
        median (confidence interval 95%)
    99999 (135.1 to 99999)
    99999 (122.9 to 99999)
    Statistical analysis title
    		 Statistical Analysis for EQ-5D
    Comparison groups
    Oral Azacitidine Plus Best Supportive Care v Placebo Plus Best Supportive Care
    Number of subjects included in analysis
    442
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.7522 [3]
    Method
    		 Regression, Cox
    Parameter type
    		 Hazard ratio (HR)
    Point estimate
    0.9345
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6136
         upper limit
    		 1.4231
    Notes
    [3] - Stratification factors: • Age (at induction therapy): 55 to 64 years and ≥ 65 years • Prior history of MDS: yes/no • Cytogenetic risk (at induction therapy): intermediate-risk/poor-risk • Received consolidation therapy following induction: yes/no

    Secondary: Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year

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    End point title
    		 Healthcare Resource Utilization (HRU): Rate of Hospital Events Per Person Year
    End point description
    HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    236
    233
    Units: Hospitalizations per person-years
        number (confidence interval 95%)
    0.36 (0.31 to 0.42)
    0.63 (0.54 to 0.74)
    No statistical analyses for this end point

    Secondary: Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year

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    End point title
    		 Healthcare Resource Utilization (HRU): Number of Days Hospitalized Per Person-Year
    End point description
    HRU is defined as any consumption of healthcare resources directly or indirectly related to the treatment of the patient. HRU is a key component to understand treatment costs and budget impact of new treatments from a provider perspective.
    End point type
    Secondary
    End point timeframe
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    End point values
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Number of subjects analysed
    236
    233
    Units: Days per person-years
        number (confidence interval 95%)
    6.00 (5.78 to 6.22)
    13.13 (12.68 to 13.60)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From day 1 (randomization) up to data cut off date of 06 August 2024; approximately 135.5 months
    Adverse event reporting additional description
    The number at Risk for All-Cause Mortality represents all Randomized Participants. The number at Risk for Serious Adverse Events and Other (Not Including Serious) Adverse Events represents all participants that received at least 1 dose of study medication
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27
    Reporting groups
    Reporting group title
    Oral Azacitidine Plus Best Supportive Care
    Reporting group description
    		 Participants received 300 mg azacitidine tablets once a day (QD) for the first 14 days of each 28-day treatment cycle until discontinuation, which includes the following reasons: disease relapse, withdrawal of consent, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, death, lost to follow-up, or protocol violation or until the end of the study.

    Reporting group title
    Placebo Plus Best Supportive Care
    Reporting group description
    		 Participants received identically matching placebo tablets QD for the first 14 days of each 28-day treatment cycle until no longer receiving benefit, withdrawal of consent, disease relapse, adverse events, participant became eligible for allogeneic bone marrow or stem cell transplantation during the treatment period, lost to follow-up, or protocol violation or until the end of the study.

    Serious adverse events
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Total subjects affected by serious adverse events
         subjects affected / exposed
    110 / 236 (46.61%)
    109 / 233 (46.78%)
         number of deaths (all causes)
    171
    175
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Central nervous system leukaemia
         subjects affected / exposed
    2 / 236 (0.85%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Basal cell carcinoma
         subjects affected / exposed
    4 / 236 (1.69%)
    3 / 233 (1.29%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute myeloid leukaemia recurrent
         subjects affected / exposed
    37 / 236 (15.68%)
    58 / 233 (24.89%)
         occurrences causally related to treatment / all
    0 / 37
    0 / 58
         deaths causally related to treatment / all
    0 / 3
    0 / 3
    Acute myeloid leukaemia
         subjects affected / exposed
    2 / 236 (0.85%)
    5 / 233 (2.15%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 5
         deaths causally related to treatment / all
    0 / 1
    0 / 4
    Cholangiocarcinoma
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chloroma
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gliomatosis cerebri
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Malignant melanoma
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningioma
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma
         subjects affected / exposed
    0 / 236 (0.00%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Prostatic adenoma
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of lung
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Squamous cell carcinoma of skin
         subjects affected / exposed
    2 / 236 (0.85%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypotension
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Peripheral artery stenosis
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombophlebitis
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    2 / 236 (0.85%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Multiple organ dysfunction syndrome
         subjects affected / exposed
    1 / 236 (0.42%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 2
    General physical health deterioration
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Pyrexia
         subjects affected / exposed
    6 / 236 (2.54%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to vaccine
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dyspnoea
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epistaxis
         subjects affected / exposed
    0 / 236 (0.00%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary haemorrhage
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Confusional state
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Investigations
    C-reactive protein increased
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General physical condition abnormal
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Troponin increased
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Weight decreased
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Hip fracture
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Foot fracture
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cataract traumatic
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chemical peritonitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subdural haematoma
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal fracture
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post-traumatic pain
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Hydrocele
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve disease
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    3 / 236 (1.27%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiogenic shock
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Stress cardiomyopathy
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebral ischaemia
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral haemorrhage
         subjects affected / exposed
    2 / 236 (0.85%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 2
    0 / 1
    Central nervous system inflammation
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ischaemic cerebral infarction
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 236 (0.85%)
    3 / 233 (1.29%)
         occurrences causally related to treatment / all
    1 / 2
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Disseminated intravascular coagulation
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile neutropenia
         subjects affected / exposed
    16 / 236 (6.78%)
    9 / 233 (3.86%)
         occurrences causally related to treatment / all
    5 / 16
    2 / 9
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphadenitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytopenia
         subjects affected / exposed
    2 / 236 (0.85%)
    3 / 233 (1.29%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancytopenia
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thrombocytosis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Eye disorders
    Iridocyclitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Keratitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ulcerative keratitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Crohn's disease
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    3 / 236 (1.27%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    2 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis eosinophilic
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ileus paralytic
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower gastrointestinal haemorrhage
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Melaena
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic colitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal haemorrhage
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    1 / 236 (0.42%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis
         subjects affected / exposed
    3 / 236 (1.27%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 236 (0.00%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis chronic
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperbilirubinaemia
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Acute febrile neutrophilic dermatosis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    3 / 236 (1.27%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bone pain
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint effusion
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoporotic fracture
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myalgia
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spinal pain
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Atypical pneumonia
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial infection
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial sepsis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    4 / 236 (1.69%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholecystitis infective
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clostridium difficile infection
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related sepsis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endophthalmitis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis salmonella
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis Escherichia coli
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal infection
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    3 / 236 (1.27%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Klebsiella sepsis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Lung abscess
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia aspiration
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia
         subjects affected / exposed
    13 / 236 (5.51%)
    7 / 233 (3.00%)
         occurrences causally related to treatment / all
    8 / 14
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neutropenic sepsis
         subjects affected / exposed
    2 / 236 (0.85%)
    2 / 233 (0.86%)
         occurrences causally related to treatment / all
    1 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pneumonia fungal
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pseudomonas infection
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory tract infection
         subjects affected / exposed
    0 / 236 (0.00%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    5 / 236 (2.12%)
    4 / 233 (1.72%)
         occurrences causally related to treatment / all
    2 / 5
    0 / 5
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    Septic shock
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Staphylococcal infection
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Superinfection bacterial
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Wound infection
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection bacterial
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dehydration
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hyperkalaemia
         subjects affected / exposed
    2 / 236 (0.85%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypocalcaemia
         subjects affected / exposed
    1 / 236 (0.42%)
    0 / 233 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 236 (0.42%)
    1 / 233 (0.43%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Oral Azacitidine Plus Best Supportive Care Placebo Plus Best Supportive Care
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    235 / 236 (99.58%)
    224 / 233 (96.14%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute myeloid leukaemia recurrent
         subjects affected / exposed
    115 / 236 (48.73%)
    126 / 233 (54.08%)
         occurrences all number
    117
    128
    Vascular disorders
    Hypertension
         subjects affected / exposed
    19 / 236 (8.05%)
    16 / 233 (6.87%)
         occurrences all number
    21
    18
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    44 / 236 (18.64%)
    12 / 233 (5.15%)
         occurrences all number
    60
    13
    Oedema peripheral
         subjects affected / exposed
    22 / 236 (9.32%)
    24 / 233 (10.30%)
         occurrences all number
    26
    33
    Fatigue
         subjects affected / exposed
    71 / 236 (30.08%)
    44 / 233 (18.88%)
         occurrences all number
    104
    56
    Influenza like illness
         subjects affected / exposed
    12 / 236 (5.08%)
    7 / 233 (3.00%)
         occurrences all number
    19
    10
    Pyrexia
         subjects affected / exposed
    37 / 236 (15.68%)
    43 / 233 (18.45%)
         occurrences all number
    48
    62
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    30 / 236 (12.71%)
    39 / 233 (16.74%)
         occurrences all number
    47
    47
    Dyspnoea
         subjects affected / exposed
    13 / 236 (5.51%)
    14 / 233 (6.01%)
         occurrences all number
    16
    20
    Epistaxis
         subjects affected / exposed
    16 / 236 (6.78%)
    17 / 233 (7.30%)
         occurrences all number
    20
    21
    Oropharyngeal pain
         subjects affected / exposed
    15 / 236 (6.36%)
    19 / 233 (8.15%)
         occurrences all number
    19
    23
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    17 / 236 (7.20%)
    8 / 233 (3.43%)
         occurrences all number
    17
    10
    Insomnia
         subjects affected / exposed
    22 / 236 (9.32%)
    23 / 233 (9.87%)
         occurrences all number
    26
    25
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    12 / 236 (5.08%)
    4 / 233 (1.72%)
         occurrences all number
    15
    7
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    14 / 236 (5.93%)
    4 / 233 (1.72%)
         occurrences all number
    16
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    25 / 236 (10.59%)
    26 / 233 (11.16%)
         occurrences all number
    36
    34
    Dizziness
         subjects affected / exposed
    25 / 236 (10.59%)
    21 / 233 (9.01%)
         occurrences all number
    32
    22
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    51 / 236 (21.61%)
    42 / 233 (18.03%)
         occurrences all number
    77
    59
    Febrile neutropenia
         subjects affected / exposed
    14 / 236 (5.93%)
    10 / 233 (4.29%)
         occurrences all number
    16
    12
    Thrombocytopenia
         subjects affected / exposed
    81 / 236 (34.32%)
    62 / 233 (26.61%)
         occurrences all number
    185
    73
    Neutropenia
         subjects affected / exposed
    104 / 236 (44.07%)
    61 / 233 (26.18%)
         occurrences all number
    420
    87
    Leukopenia
         subjects affected / exposed
    27 / 236 (11.44%)
    19 / 233 (8.15%)
         occurrences all number
    62
    28
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    32 / 236 (13.56%)
    15 / 233 (6.44%)
         occurrences all number
    51
    18
    Constipation
         subjects affected / exposed
    92 / 236 (38.98%)
    56 / 233 (24.03%)
         occurrences all number
    181
    75
    Abdominal pain upper
         subjects affected / exposed
    23 / 236 (9.75%)
    13 / 233 (5.58%)
         occurrences all number
    31
    15
    Flatulence
         subjects affected / exposed
    12 / 236 (5.08%)
    4 / 233 (1.72%)
         occurrences all number
    13
    6
    Haemorrhoids
         subjects affected / exposed
    12 / 236 (5.08%)
    4 / 233 (1.72%)
         occurrences all number
    17
    4
    Dyspepsia
         subjects affected / exposed
    12 / 236 (5.08%)
    5 / 233 (2.15%)
         occurrences all number
    12
    7
    Diarrhoea
         subjects affected / exposed
    119 / 236 (50.42%)
    50 / 233 (21.46%)
         occurrences all number
    465
    79
    Nausea
         subjects affected / exposed
    153 / 236 (64.83%)
    54 / 233 (23.18%)
         occurrences all number
    368
    78
    Stomatitis
         subjects affected / exposed
    8 / 236 (3.39%)
    12 / 233 (5.15%)
         occurrences all number
    9
    14
    Vomiting
         subjects affected / exposed
    142 / 236 (60.17%)
    23 / 233 (9.87%)
         occurrences all number
    308
    25
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    16 / 236 (6.78%)
    18 / 233 (7.73%)
         occurrences all number
    21
    18
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    27 / 236 (11.44%)
    24 / 233 (10.30%)
         occurrences all number
    39
    35
    Arthralgia
         subjects affected / exposed
    45 / 236 (19.07%)
    32 / 233 (13.73%)
         occurrences all number
    55
    44
    Pain in extremity
         subjects affected / exposed
    28 / 236 (11.86%)
    12 / 233 (5.15%)
         occurrences all number
    32
    13
    Infections and infestations
    Influenza
         subjects affected / exposed
    17 / 236 (7.20%)
    7 / 233 (3.00%)
         occurrences all number
    19
    10
    Nasopharyngitis
         subjects affected / exposed
    20 / 236 (8.47%)
    16 / 233 (6.87%)
         occurrences all number
    36
    20
    Bronchitis
         subjects affected / exposed
    14 / 236 (5.93%)
    9 / 233 (3.86%)
         occurrences all number
    18
    10
    Upper respiratory tract infection
         subjects affected / exposed
    32 / 236 (13.56%)
    32 / 233 (13.73%)
         occurrences all number
    49
    59
    Rhinitis
         subjects affected / exposed
    13 / 236 (5.51%)
    4 / 233 (1.72%)
         occurrences all number
    18
    5
    Oral herpes
         subjects affected / exposed
    13 / 236 (5.51%)
    6 / 233 (2.58%)
         occurrences all number
    15
    10
    Urinary tract infection
         subjects affected / exposed
    18 / 236 (7.63%)
    13 / 233 (5.58%)
         occurrences all number
    28
    16
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    31 / 236 (13.14%)
    15 / 233 (6.44%)
         occurrences all number
    42
    16
    Hypokalaemia
         subjects affected / exposed
    21 / 236 (8.90%)
    20 / 233 (8.58%)
         occurrences all number
    34
    22

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    08 Nov 2018
    The primary purpose of this protocol amendment is to add an extension phase (EP) to allow all subjects who are on treatment with oral azacitidine and demonstrating clinical benefit in this protocol to continue to do so in an extension phase. In addition, all subjects who were discontinued from the treatment phase (irrespective of randomization arm) and continuing in the Follow-up Phase, will be followed for survival for at least another 12 months, until death, withdrawal of consent, study closure or until the subject is lost to follow-up.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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