A Study of Venetoclax in Combination With Azacitidine Versus Azacitidine in Treatment Naïve Participants With Acute Myeloid Leukemia Who Are Ineligible for Standard Induction Therapy (Viale-a)

• ClinicalTrials.gov Identifier: NCT02993523
• Recruitment Status: Active, not recruiting
• First Posted: December 15, 2016
• Results First Posted: January 27, 2023
• Last Update Posted: July 3, 2023
• Sponsor: AbbVie
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): AbbVie

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Acute Myeloid Leukemia (AML)
• Interventions: Drug: Azacitidine; Drug: Venetoclax; Drug: Placebo
• Enrollment: 443

Participant Flow

Recruitment Details	Participants were randomized in Group 1 per original protocol stratified by age (18 - < 75, ≥ 75), and region (US, EU, Japan (JP), Rest of world (ROW)) and Group 2 during or after Amendment 1 stratified by age (18 - < 75, ≥ 75), cytogenetic risk (intermediate, poor) and region (US, EU, China, JP, ROW).
Pre-assignment Details	Total of 443 participants were enrolled. 433 participants were randomized in Group 1 and Group 2 to receive placebo or venetoclax 100/200/400mg+azacitidine 75mg/m^2. 10 participants in open-label China cohort received venetoclax 400 mg + azacitidine 75 mg/m^2 up to data cut-off date: 01 December 2021. This study is ongoing.

Arm/Group Title	Group 1: Placebo + Azacitidine 75 mg/m^2	Group 1: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Group 2: Placebo + Azacitidine 75 mg/m^2	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
Arm/Group Description	Participants enrolled under original protocol received venetoclax-matching placebo, orally, once daily (QD), from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, subcutaneously (SC) or intravenously (IV), QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants enrolled under original protocol received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Period Title: Overall Study
Started	1	1	145	286	10
Completed	0	0	1	48	4
Not Completed	1	1	144	238	6
Reason Not Completed
Withdrew Consent	0	0	2	9	0
Lost to Follow-up	0	0	3	6	0
Death	1	1	138	222	6
Reason not Specified	0	0	1	1	0

Baseline Characteristics

Arm/Group Title		Group 1: Placebo + Azacitidine 75 mg/m^2	Group 1: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Group 2: Placebo + Azacitidine 75 mg/m^2	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2	Total
Arm/Group Description		Participants enrolled under original protocol received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants enrolled under original protocol received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Total of all reporting groups
Overall Number of Baseline Participants		1	1	145	286	10	443
Baseline Analysis Population Description		Full Analysis Set included all Group 1 and 2 participants randomized by Interactive Voice Response System (IVRS)/Interactive Web Response System (IWRS) (exclude the open-label China safety cohort). Open-Label China Safety Cohort included participants who received at least one dose of venetoclax.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	1 participants	1 participants	145 participants	286 participants	10 participants	443 participants
		61.0 [1] (NA)	65.0 [2] (NA)	75.1 (5.70)	75.6 (6.08)	70.2 (7.44)	75.2 (6.08)
		[1] Standard deviation (SD) was not estimable for 1 participant.; [2] SD was not estimable for 1 participant.
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	145 participants	286 participants	10 participants	443 participants
	Female	1 100.0%	0 0.0%	58 40.0%	114 39.9%	4 40.0%	177 40.0%
	Male	0 0.0%	1 100.0%	87 60.0%	172 60.1%	6 60.0%	266 60.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	1 participants	1 participants	145 participants	286 participants	10 participants	443 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	1 0.7%	0 0.0%	0 0.0%	1 0.2%
	Asian	0 0.0%	0 0.0%	33 22.8%	66 23.1%	10 100.0%	109 24.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Black or African American	1 100.0%	0 0.0%	2 1.4%	3 1.0%	0 0.0%	6 1.4%
	White	0 0.0%	1 100.0%	109 75.2%	217 75.9%	0 0.0%	327 73.8%
	More than one race	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%

Outcome Measures

1. Primary Outcome

Title	Overall Survival (OS)
Description	OS is defined as the number of days from the date of randomization to the date of death. Log rank test was used to compare the OS distribution between two treatment arms. Cox regression was used to report the hazard ratio.
Time Frame	From the study start up to death or alive or lost to follow-up (up to approximately 4.8 years; data cut off date: 1 December 2021)

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all Group 2 participants randomized by IVRS/IWRS (exclude the open-label China safety cohort).

Arm/Group Title	Group 2: Placebo + Azacitidine 75 mg/m^2	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2
Arm/Group Description:	Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Overall Number of Participants Analyzed	145	286
Median (95% Confidence Interval); Unit of Measure: months
	9.6; (7.4 to 12.7)	14.7; (12.1 to 18.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 2: Placebo + Azacitidine 75 mg/m^2, Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Stratified log-rank test stratified by age (18 - < 75, ≥ 75) and cytogenetic risk (intermediate, poor).
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.580
	Confidence Interval	(2-Sided) 95%; 0.465 to 0.723
	Estimation Comments	HR from Cox proportional hazards model stratified by age (18 - < 75, ≥ 75) and cytogenetic risk (intermediate, poor).

2. Primary Outcome

Title	Percentage of Participants With Complete Remission (CR) and Complete Remission With Incomplete Marrow Recovery (CRi)
Description	CR and CRi was calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count >10^3/ microliter (mcL), platelets >10^5/mcL, red cell transfusion independence, and bone marrow with <5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of ≤10^3/mcL or platelets ≤10^5/mcL. Percentages are rounded off to whole number at the nearest decimal.
Time Frame	From the study start up to death (up to approximately 4.8 years; data cut-off date: 1 December 2021)

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all Group 2 participants randomized by IVRS/IWRS (exclude the open-label China safety cohort). Open-Label China Safety Cohort included participants who received at least one dose of venetoclax. Data is reported for Group 2 and Open-label China Cohort.

Arm/Group Title	Group 2: Placebo + Azacitidine 75 mg/m^2	Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2	Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
Arm/Group Description:	Participants received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, from Day 3 to Day 28 of each 28-day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).	Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
Overall Number of Participants Analyzed	145	286	10
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
CR	17.9; (12.1 to 25.2)	38.8; (33.1 to 44.7)	60.0; (26.2 to 87.8)
CRi	11.0; (6.4 to 17.3)	28.0; (22.8 to 33.6)	20.0; (2.5 to 55.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Group 2: Placebo + Azacitidine 75 mg/m^2, Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	Cochran-Mantel-Haenszel (CMH) test stratified by age (18 - < 75, ≥ 75) and cytogenetic risk (intermediate, poor).

3. Secondary Outcome

Title	Event-free Survival (EFS)
Description	EFS will be defined as the number of days from randomization to the date of progressive disease, relapse from CR or CRi, treatment failure or death from any cause.
Time Frame	Measured up to 2 years after the last participant is randomized

Outcome Measure Data Not Reported

4. Secondary Outcome

Title	Global Health Status/Quality of Life (GHS/QoL)
Description	Improvement in GHS/QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).
Time Frame	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last subject last visit

Outcome Measure Data Not Reported

5. Secondary Outcome

Title	Percentage of Participants Achieving Composite Complete Remission (CR or CRi)
Description	This will be calculated based on current International Working Group (IWG) criteria. CR is defined as absolute neutrophil count > 10^3/mcL, platelets > 10^5/mcL, red cell transfusion independence, and bone marrow with < 5% blasts. CRi is defined as bone marrow with less than 5% blasts, and absolute neutrophils of <= 10^3/mcL or platelets <= 10^5/mcL.
Time Frame	Up to 6 months after the first 225 participants are randomized

Outcome Measure Data Not Reported

6. Secondary Outcome

Title	Complete Remission or Complete Remission With Partial Hematologic Recovery Rate (CR+CRh)
Description	A response of CRh is defined as Bone marrow with <5% blasts, peripheral blood neutrophil count >0.5*10^3/mcL and peripheral blood platelet count >0.5*10^5/mcL.
Time Frame	Measured up to 2 years after the last participant is randomized

Outcome Measure Data Not Reported

7. Secondary Outcome

Title	Post Baseline Transfusion Independence Rate
Description	Transfusion Independence is defined as a period of 56 days with no transfusion between first dose of study drug and the last dose of study drug + 30 days. The rate of conversion for red blood cells (RBC) and platelets is defined as percentage of participants being post-baseline transfusion independent from baseline transfusion dependence.
Time Frame	Measured up to 2 years after the last participant is randomized

Outcome Measure Data Not Reported

8. Secondary Outcome

Title	Complete Remission (CR) Rate
Description	The percentage of participants with complete remission (CR) will be calculated based on the modified IWG criteria for AML.
Time Frame	Measured up to 2 years after the last participant is randomized

Outcome Measure Data Not Reported

9. Secondary Outcome

Title	Fatigue/Quality of Life (QoL)
Description	Fatigue QoL will be assessed using the Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form (SF) 7a global fatigue score
Time Frame	Measured at participant's Day 1 of Cycle 1 (each cycle is 28 days) and at Day 1 of every Cycle thereafter for up to 2 years following the last participant last visit

Outcome Measure Data Not Reported

Adverse Events

Time Frame	From the study start until data cut-off date: 01 December 2021 (up to approximately 4.8 years)
Adverse Event Reporting Description	Safety analysis set included all Group 1 and Group 2 participants (exclude the open-label China safety cohort) who took at least one dose of venetoclax/placebo and azacitidine combination. As pre-specified in SAP the data is reported combined for both Group 1 and Group 2 participants who received either placebo plus azacitidine or venetoclax plus azacitidine. Open-Label China Safety Cohort included participants who received at least one dose of venetoclax in combination with azacitidine.
Arm/Group Title	Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2		Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2		Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
Arm/Group Description	Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax-matching placebo, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).		Participants enrolled under original protocol and enrolled during or after protocol amendment 1 received venetoclax 100 mg, once orally, on Day 1 of Cycle 1 followed by venetoclax 200 mg, once orally, on Day 2 of Cycle 1 and venetoclax 400 mg, orally, QD, on Day 3 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC or IV, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).		Participants received venetoclax 400 mg, orally, QD, from Day 1 to Day 28 of each 28 day cycle along with azacitidine 75 mg/m^2, SC, QD for 7 days from Day 1 of each 28-day cycle until documented disease progression, unacceptable toxicity, withdrawal of consent, or other protocol criteria for discontinuation (whichever occurred first).
All-Cause Mortality
	Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2		Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2		Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	140/144 (97.22%)		226/283 (79.86%)		6/10 (60.00%)
Serious Adverse Events
	Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2		Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2		Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	111/144 (77.08%)		242/283 (85.51%)		7/10 (70.00%)
Blood and lymphatic system disorders
ANAEMIA † 1	9/144 (6.25%)	13	19/283 (6.71%)	23	0/10 (0.00%)	0
CYTOPENIA † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
DISSEMINATED INTRAVASCULAR COAGULATION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
FEBRILE NEUTROPENIA † 1	15/144 (10.42%)	21	88/283 (31.10%)	132	2/10 (20.00%)	2
HAEMOLYSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LEUKOCYTOSIS † 1	3/144 (2.08%)	3	1/283 (0.35%)	1	0/10 (0.00%)	0
LEUKOPENIA † 1	0/144 (0.00%)	0	4/283 (1.41%)	5	0/10 (0.00%)	0
NEUTROPENIA † 1	4/144 (2.78%)	4	14/283 (4.95%)	15	3/10 (30.00%)	3
PANCYTOPENIA † 1	0/144 (0.00%)	0	5/283 (1.77%)	5	0/10 (0.00%)	0
THROMBOCYTOPENIA † 1	3/144 (2.08%)	3	14/283 (4.95%)	14	3/10 (30.00%)	4
Cardiac disorders
ACUTE CORONARY SYNDROME † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
ACUTE MYOCARDIAL INFARCTION † 1	3/144 (2.08%)	4	2/283 (0.71%)	2	0/10 (0.00%)	0
ANGINA PECTORIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ANGINA UNSTABLE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ATRIAL FIBRILLATION † 1	2/144 (1.39%)	2	13/283 (4.59%)	15	0/10 (0.00%)	0
ATRIAL FLUTTER † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ATRIOVENTRICULAR BLOCK † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CARDIAC ARREST † 1	2/144 (1.39%)	2	3/283 (1.06%)	3	0/10 (0.00%)	0
CARDIAC FAILURE † 1	3/144 (2.08%)	3	7/283 (2.47%)	8	1/10 (10.00%)	1
CARDIAC FAILURE ACUTE † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
CARDIAC FAILURE CONGESTIVE † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
CARDIAC TAMPONADE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CARDIO-RESPIRATORY ARREST † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CARDIOVASCULAR DISORDER † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CARDIOVASCULAR INSUFFICIENCY † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ISCHAEMIC CARDIOMYOPATHY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LEFT VENTRICULAR DYSFUNCTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MYOCARDIAL INFARCTION † 1	1/144 (0.69%)	1	2/283 (0.71%)	3	0/10 (0.00%)	0
MYOCARDIAL ISCHAEMIA † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
MYOCARDIAL OEDEMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PERICARDIAL EFFUSION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PERICARDITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RIGHT VENTRICULAR FAILURE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
SUPRAVENTRICULAR EXTRASYSTOLES † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SUPRAVENTRICULAR TACHYCARDIA † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
TORSADE DE POINTES † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
VENTRICULAR TACHYCARDIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Ear and labyrinth disorders
VERTIGO † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
Gastrointestinal disorders
ABDOMINAL PAIN UPPER † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
ANAL FISTULA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
COLITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
COLITIS ISCHAEMIC † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CONSTIPATION † 1	2/144 (1.39%)	3	3/283 (1.06%)	3	0/10 (0.00%)	0
DIARRHOEA † 1	3/144 (2.08%)	4	6/283 (2.12%)	6	0/10 (0.00%)	0
DYSPEPSIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ENTEROCOLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
GASTRITIS HAEMORRHAGIC † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
GASTRODUODENITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
GASTROINTESTINAL HAEMORRHAGE † 1	2/144 (1.39%)	3	2/283 (0.71%)	3	0/10 (0.00%)	0
HAEMATEMESIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HAEMORRHOIDS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
HYPERTROPHIC ANAL PAPILLA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ILEUS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
ILEUS PARALYTIC † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INGUINAL HERNIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INTESTINAL HAEMORRHAGE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INTESTINAL OBSTRUCTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LOWER GASTROINTESTINAL HAEMORRHAGE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MELAENA † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
NAUSEA † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
NECROTISING COLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
NEUTROPENIC COLITIS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
PALATAL ULCER † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PANCREATITIS ACUTE † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
PROCTALGIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PROCTITIS † 1	2/144 (1.39%)	2	0/283 (0.00%)	0	0/10 (0.00%)	0
RECTAL HAEMORRHAGE † 1	1/144 (0.69%)	2	0/283 (0.00%)	0	0/10 (0.00%)	0
SMALL INTESTINAL OBSTRUCTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
STOMATITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
VOMITING † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
General disorders
ASTHENIA † 1	0/144 (0.00%)	0	4/283 (1.41%)	4	0/10 (0.00%)	0
CATHETER SITE HAEMORRHAGE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CHILLS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
DEATH † 1	2/144 (1.39%)	2	4/283 (1.41%)	4	0/10 (0.00%)	0
DISCOMFORT † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
FATIGUE † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
GENERAL PHYSICAL HEALTH DETERIORATION † 1	5/144 (3.47%)	6	5/283 (1.77%)	6	0/10 (0.00%)	0
IMPAIRED SELF-CARE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INCARCERATED HERNIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INJECTION SITE EXTRAVASATION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INJECTION SITE INFLAMMATION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MUCOSAL INFLAMMATION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
MULTIPLE ORGAN DYSFUNCTION SYNDROME † 1	1/144 (0.69%)	2	2/283 (0.71%)	3	0/10 (0.00%)	0
NON-CARDIAC CHEST PAIN † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
OEDEMA PERIPHERAL † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
PERIPHERAL SWELLING † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PYREXIA † 1	3/144 (2.08%)	3	9/283 (3.18%)	10	0/10 (0.00%)	0
SUDDEN CARDIAC DEATH † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
SUDDEN DEATH † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
SYSTEMIC INFLAMMATORY RESPONSE SYNDROME † 1	2/144 (1.39%)	2	3/283 (1.06%)	4	0/10 (0.00%)	0
Hepatobiliary disorders
CHOLECYSTITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
CHOLECYSTITIS ACUTE † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
CHOLELITHIASIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATIC CONGESTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATIC FUNCTION ABNORMAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATITIS ACUTE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATITIS CHOLESTATIC † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Immune system disorders
DRUG HYPERSENSITIVITY † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
Infections and infestations
ABSCESS FUNGAL † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ABSCESS LIMB † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ACINETOBACTER BACTERAEMIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ACUTE SINUSITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ALVEOLAR OSTEITIS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ANAL ABSCESS † 1	0/144 (0.00%)	0	3/283 (1.06%)	5	0/10 (0.00%)	0
ANORECTAL CELLULITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
ASPERGILLUS INFECTION † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
ATYPICAL PNEUMONIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BACTERAEMIA † 1	0/144 (0.00%)	0	7/283 (2.47%)	9	0/10 (0.00%)	0
BRONCHIOLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BRONCHITIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
BRONCHITIS BACTERIAL † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
BRONCHITIS MORAXELLA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BRONCHITIS VIRAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BRONCHOPULMONARY ASPERGILLOSIS † 1	2/144 (1.39%)	2	3/283 (1.06%)	3	0/10 (0.00%)	0
BURKHOLDERIA INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CAMPYLOBACTER GASTROENTERITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CANDIDA SEPSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
CANDIDURIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CELLULITIS † 1	4/144 (2.78%)	4	7/283 (2.47%)	9	0/10 (0.00%)	0
CELLULITIS OF MALE EXTERNAL GENITAL ORGAN † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CELLULITIS ORBITAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CELLULITIS STAPHYLOCOCCAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CITROBACTER INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CLOSTRIDIAL SEPSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CLOSTRIDIUM DIFFICILE COLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
CORONA VIRUS INFECTION † 1	2/144 (1.39%)	2	2/283 (0.71%)	2	0/10 (0.00%)	0
DERMATITIS INFECTED † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
DIVERTICULITIS † 1	1/144 (0.69%)	1	6/283 (2.12%)	9	0/10 (0.00%)	0
EAR INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ENDOCARDITIS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ENTEROBACTER PNEUMONIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ENTEROCOCCAL INFECTION † 1	1/144 (0.69%)	1	2/283 (0.71%)	3	0/10 (0.00%)	0
ENTEROCOCCAL SEPSIS † 1	2/144 (1.39%)	2	1/283 (0.35%)	1	0/10 (0.00%)	0
ERYSIPELAS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ESCHERICHIA BACTERAEMIA † 1	1/144 (0.69%)	1	7/283 (2.47%)	8	0/10 (0.00%)	0
ESCHERICHIA INFECTION † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
ESCHERICHIA SEPSIS † 1	2/144 (1.39%)	2	9/283 (3.18%)	10	0/10 (0.00%)	0
ESCHERICHIA URINARY TRACT INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	3	0/10 (0.00%)	0
EYE INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
FUNGAL SEPSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
GASTROENTERITIS † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
GASTROENTERITIS SALMONELLA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
GASTROINTESTINAL INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
GINGIVITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
HERPES SIMPLEX † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
INFECTIOUS PLEURAL EFFUSION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INFECTIOUS THYROIDITIS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
INFLUENZA † 1	2/144 (1.39%)	2	8/283 (2.83%)	9	0/10 (0.00%)	0
INTERVERTEBRAL DISCITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
KLEBSIELLA BACTERAEMIA † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
KLEBSIELLA INFECTION † 1	2/144 (1.39%)	2	2/283 (0.71%)	3	0/10 (0.00%)	0
KLEBSIELLA SEPSIS † 1	1/144 (0.69%)	1	2/283 (0.71%)	3	0/10 (0.00%)	0
LIVER ABSCESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LUNG INFECTION † 1	3/144 (2.08%)	3	10/283 (3.53%)	10	2/10 (20.00%)	2
MEDICAL DEVICE SITE CELLULITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MENINGITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
NEUTROPENIC SEPSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ORAL HERPES † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ORCHITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
OROPHARYNGEAL CANDIDIASIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
OSTEOMYELITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
OTITIS MEDIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PARAINFLUENZAE VIRUS INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PAROTITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PERICORONITIS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
PHARYNGITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PHARYNGOTONSILLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PNEUMOCYSTIS JIROVECII INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PNEUMONIA † 1	35/144 (24.31%)	46	55/283 (19.43%)	71	0/10 (0.00%)	0
PNEUMONIA FUNGAL † 1	1/144 (0.69%)	1	4/283 (1.41%)	4	0/10 (0.00%)	0
PNEUMONIA KLEBSIELLA † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
PNEUMONIA PNEUMOCOCCAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PNEUMONIA VIRAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
POST PROCEDURAL INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PROTEUS INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PSEUDOMONAL BACTERAEMIA † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PSEUDOMONAL SEPSIS † 1	2/144 (1.39%)	2	2/283 (0.71%)	2	1/10 (10.00%)	1
PSEUDOMONAS INFECTION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PSOAS ABSCESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
PULMONARY MYCOSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PULMONARY NOCARDIOSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PULPITIS DENTAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RECTAL ABSCESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RESPIRATORY SYNCYTIAL VIRUS INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RESPIRATORY TRACT INFECTION † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
RESPIRATORY TRACT INFECTION VIRAL † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
RHINITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RHINOVIRUS INFECTION † 1	1/144 (0.69%)	2	2/283 (0.71%)	2	0/10 (0.00%)	0
SEPSIS † 1	12/144 (8.33%)	14	20/283 (7.07%)	29	0/10 (0.00%)	0
SEPTIC SHOCK † 1	1/144 (0.69%)	1	8/283 (2.83%)	11	0/10 (0.00%)	0
SINUSITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
SKIN INFECTION † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
SOFT TISSUE INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
STAPHYLOCOCCAL BACTERAEMIA † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
STAPHYLOCOCCAL INFECTION † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
STAPHYLOCOCCAL SEPSIS † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
STREPTOCOCCAL BACTERAEMIA † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
STREPTOCOCCAL SEPSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SUBCUTANEOUS ABSCESS † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
SYSTEMIC CANDIDA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SYSTEMIC INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SYSTEMIC MYCOSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
TONSILLITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
TOOTH ABSCESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
UPPER RESPIRATORY TRACT INFECTION † 1	1/144 (0.69%)	1	5/283 (1.77%)	5	0/10 (0.00%)	0
URINARY TRACT INFECTION † 1	3/144 (2.08%)	6	10/283 (3.53%)	11	0/10 (0.00%)	0
URINARY TRACT INFECTION BACTERIAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
URINARY TRACT INFECTION ENTEROCOCCAL † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
UROSEPSIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
VASCULAR DEVICE INFECTION † 1	2/144 (1.39%)	2	5/283 (1.77%)	5	0/10 (0.00%)	0
WATERHOUSE-FRIDERICHSEN SYNDROME † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
WOUND INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
WOUND INFECTION STAPHYLOCOCCAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Injury, poisoning and procedural complications
ARTERIAL BYPASS OCCLUSION † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
EXTRADURAL HAEMATOMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
FACIAL BONES FRACTURE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
FALL † 1	3/144 (2.08%)	3	3/283 (1.06%)	4	0/10 (0.00%)	0
FEMORAL NECK FRACTURE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
HEAD INJURY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HUMERUS FRACTURE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
INCISION SITE HAEMATOMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
INJURY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LACERATION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LIGAMENT SPRAIN † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LUMBAR VERTEBRAL FRACTURE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
PELVIC FRACTURE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PUBIS FRACTURE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SPINAL FRACTURE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SUBARACHNOID HAEMORRHAGE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
SUBDURAL HAEMATOMA † 1	1/144 (0.69%)	2	2/283 (0.71%)	2	0/10 (0.00%)	0
SUBDURAL HAEMORRHAGE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
TRANSFUSION REACTION † 1	2/144 (1.39%)	2	2/283 (0.71%)	2	0/10 (0.00%)	0
VASCULAR PSEUDOANEURYSM † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
WOUND † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
Investigations
ALANINE AMINOTRANSFERASE INCREASED † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
ASPARTATE AMINOTRANSFERASE INCREASED † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
BLOOD BILIRUBIN INCREASED † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BLOOD CREATININE INCREASED † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
C-REACTIVE PROTEIN INCREASED † 1	1/144 (0.69%)	1	3/283 (1.06%)	3	0/10 (0.00%)	0
CLOSTRIDIUM TEST POSITIVE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
COMPUTERISED TOMOGRAM HEAD ABNORMAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
GENERAL PHYSICAL CONDITION ABNORMAL † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
NEUTROPHIL COUNT DECREASED † 1	0/144 (0.00%)	0	2/283 (0.71%)	3	0/10 (0.00%)	0
PLATELET COUNT DECREASED † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
POLYOMAVIRUS TEST POSITIVE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
STAPHYLOCOCCUS TEST POSITIVE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
WEIGHT DECREASED † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
WHITE BLOOD CELL COUNT INCREASED † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
Metabolism and nutrition disorders
DECREASED APPETITE † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
DEHYDRATION † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
FAILURE TO THRIVE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HYPERKALAEMIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
HYPERNATRAEMIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HYPONATRAEMIA † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
HYPOVOLAEMIA † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
METABOLIC ACIDOSIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
TUMOUR LYSIS SYNDROME † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	0/10 (0.00%)	0
Musculoskeletal and connective tissue disorders
ARTHRITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BACK PAIN † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CHONDROCALCINOSIS PYROPHOSPHATE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
NECK PAIN † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
OSTEOARTHRITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PAIN IN EXTREMITY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RHEUMATOID ARTHRITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
SERONEGATIVE ARTHRITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SOFT TISSUE HAEMORRHAGE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
ADENOCARCINOMA OF COLON † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
BRAIN NEOPLASM † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ERYTHROLEUKAEMIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEPATIC CANCER STAGE IV † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MALIGNANT MELANOMA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
MALIGNANT NEOPLASM PROGRESSION † 1	5/144 (3.47%)	5	2/283 (0.71%)	2	0/10 (0.00%)	0
RENAL CANCER † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
SQUAMOUS CELL CARCINOMA OF SKIN † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Nervous system disorders
CEREBRAL HAEMATOMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
CEREBRAL HAEMORRHAGE † 1	1/144 (0.69%)	1	1/283 (0.35%)	2	0/10 (0.00%)	0
CEREBRAL INFARCTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
CEREBROVASCULAR ACCIDENT † 1	2/144 (1.39%)	2	3/283 (1.06%)	4	0/10 (0.00%)	0
COMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
DEPRESSED LEVEL OF CONSCIOUSNESS † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
DIZZINESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
DYSARTHRIA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ENCEPHALOPATHY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HAEMORRHAGE INTRACRANIAL † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	0/10 (0.00%)	0
HAEMORRHAGIC STROKE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEADACHE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HEMIPARESIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
ISCHAEMIC STROKE † 1	1/144 (0.69%)	1	2/283 (0.71%)	3	0/10 (0.00%)	0
MOTOR NEURONE DISEASE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PARESIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PERIPHERAL SENSORIMOTOR NEUROPATHY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PRESYNCOPE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
SEIZURE † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
SYNCOPE † 1	1/144 (0.69%)	1	6/283 (2.12%)	6	0/10 (0.00%)	0
Psychiatric disorders
CONFUSIONAL STATE † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
DELIRIUM † 1	1/144 (0.69%)	1	3/283 (1.06%)	3	0/10 (0.00%)	0
DEPRESSION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
MENTAL STATUS CHANGES † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Renal and urinary disorders
ACUTE KIDNEY INJURY † 1	5/144 (3.47%)	5	5/283 (1.77%)	5	0/10 (0.00%)	0
AZOTAEMIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CHRONIC KIDNEY DISEASE † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
HAEMATURIA † 1	1/144 (0.69%)	1	3/283 (1.06%)	3	0/10 (0.00%)	0
HAEMORRHAGE URINARY TRACT † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RENAL FAILURE † 1	0/144 (0.00%)	0	2/283 (0.71%)	3	0/10 (0.00%)	0
RENAL MASS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
STRANGURY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
URINARY RETENTION † 1	1/144 (0.69%)	1	1/283 (0.35%)	2	0/10 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
ACUTE RESPIRATORY DISTRESS SYNDROME † 1	0/144 (0.00%)	0	1/283 (0.35%)	2	0/10 (0.00%)	0
ACUTE RESPIRATORY FAILURE † 1	2/144 (1.39%)	3	2/283 (0.71%)	3	0/10 (0.00%)	0
ASPIRATION † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CHRONIC OBSTRUCTIVE PULMONARY DISEASE † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
EMPHYSEMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
EPISTAXIS † 1	0/144 (0.00%)	0	5/283 (1.77%)	6	0/10 (0.00%)	0
HAEMOPTYSIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
HYPOXIA † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	1/10 (10.00%)	1
LUNG CONSOLIDATION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
LUNG DISORDER † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PLEURAL EFFUSION † 1	3/144 (2.08%)	3	2/283 (0.71%)	3	0/10 (0.00%)	0
PNEUMONITIS † 1	1/144 (0.69%)	1	2/283 (0.71%)	4	0/10 (0.00%)	0
PNEUMOTHORAX † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PNEUMOTHORAX SPONTANEOUS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PULMONARY ARTERY THROMBOSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
PULMONARY EMBOLISM † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
PULMONARY OEDEMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RESPIRATORY DISTRESS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RESPIRATORY FAILURE † 1	1/144 (0.69%)	1	5/283 (1.77%)	6	0/10 (0.00%)	0
Skin and subcutaneous tissue disorders
ERYTHEMA † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RASH ERYTHEMATOUS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RASH GENERALISED † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RASH PAPULAR † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
RASH PRURITIC † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
Vascular disorders
ARTERIAL HAEMORRHAGE † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	0/10 (0.00%)	0
CIRCULATORY COLLAPSE † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
COELIAC ARTERY OCCLUSION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
DEEP VEIN THROMBOSIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	0/10 (0.00%)	0
HAEMORRHAGIC VASCULITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
HYPOTENSION † 1	2/144 (1.39%)	3	5/283 (1.77%)	5	0/10 (0.00%)	0
ORTHOSTATIC HYPOTENSION † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	0/10 (0.00%)	0
VENOUS THROMBOSIS LIMB † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	0/10 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Group 1 and Group 2: Placebo + Azacitidine 75 mg/m^2		Group 1 and Group 2: Venetoclax 100 mg/200 mg/400 mg + Azacitidine 75 mg/m^2		Open Label China Cohort: Venetoclax 400 mg + Azacitidine 75 mg/m^2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	137/144 (95.14%)		279/283 (98.59%)		10/10 (100.00%)
Blood and lymphatic system disorders
ANAEMIA † 1	24/144 (16.67%)	30	68/283 (24.03%)	102	6/10 (60.00%)	11
FEBRILE NEUTROPENIA † 1	12/144 (8.33%)	16	33/283 (11.66%)	44	3/10 (30.00%)	3
LEUKOPENIA † 1	20/144 (13.89%)	46	54/283 (19.08%)	133	10/10 (100.00%)	20
LYMPHADENOPATHY † 1	2/144 (1.39%)	2	4/283 (1.41%)	4	1/10 (10.00%)	1
LYMPHOPENIA † 1	3/144 (2.08%)	6	8/283 (2.83%)	16	1/10 (10.00%)	1
NEUTROPENIA † 1	38/144 (26.39%)	66	107/283 (37.81%)	245	5/10 (50.00%)	6
SPLENIC INFARCTION † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
THROMBOCYTOPENIA † 1	57/144 (39.58%)	94	120/283 (42.40%)	246	6/10 (60.00%)	15
Cardiac disorders
ANGINA PECTORIS † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	1/10 (10.00%)	1
ATRIAL FIBRILLATION † 1	13/144 (9.03%)	15	22/283 (7.77%)	26	0/10 (0.00%)	0
CARDIAC FAILURE CONGESTIVE † 1	0/144 (0.00%)	0	5/283 (1.77%)	5	1/10 (10.00%)	1
Ear and labyrinth disorders
VESTIBULAR DISORDER † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
Eye disorders
CATARACT † 1	0/144 (0.00%)	0	8/283 (2.83%)	8	1/10 (10.00%)	1
CONJUNCTIVAL DISORDER † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
KERATITIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	1/10 (10.00%)	1
OPTIC ATROPHY † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
VISION BLURRED † 1	1/144 (0.69%)	1	3/283 (1.06%)	4	1/10 (10.00%)	1
XEROPHTHALMIA † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
Gastrointestinal disorders
ABDOMINAL DISCOMFORT † 1	4/144 (2.78%)	4	6/283 (2.12%)	8	2/10 (20.00%)	3
ABDOMINAL DISTENSION † 1	7/144 (4.86%)	7	9/283 (3.18%)	11	1/10 (10.00%)	1
ABDOMINAL PAIN † 1	12/144 (8.33%)	14	34/283 (12.01%)	42	1/10 (10.00%)	1
ABDOMINAL PAIN UPPER † 1	5/144 (3.47%)	6	17/283 (6.01%)	19	0/10 (0.00%)	0
CONSTIPATION † 1	55/144 (38.19%)	66	121/283 (42.76%)	158	7/10 (70.00%)	9
DIARRHOEA † 1	46/144 (31.94%)	65	122/283 (43.11%)	182	5/10 (50.00%)	5
DYSPEPSIA † 1	7/144 (4.86%)	7	20/283 (7.07%)	23	0/10 (0.00%)	0
FLATULENCE † 1	3/144 (2.08%)	3	5/283 (1.77%)	6	1/10 (10.00%)	1
GINGIVAL PAIN † 1	3/144 (2.08%)	4	6/283 (2.12%)	6	2/10 (20.00%)	2
GINGIVAL SWELLING † 1	1/144 (0.69%)	2	2/283 (0.71%)	2	2/10 (20.00%)	2
HAEMORRHOIDS † 1	6/144 (4.17%)	6	29/283 (10.25%)	31	0/10 (0.00%)	0
NAUSEA † 1	53/144 (36.81%)	65	123/283 (43.46%)	178	4/10 (40.00%)	6
STOMATITIS † 1	9/144 (6.25%)	10	32/283 (11.31%)	39	0/10 (0.00%)	0
VOMITING † 1	33/144 (22.92%)	44	84/283 (29.68%)	128	5/10 (50.00%)	9
General disorders
ASTHENIA † 1	12/144 (8.33%)	17	45/283 (15.90%)	55	0/10 (0.00%)	0
FATIGUE † 1	24/144 (16.67%)	29	61/283 (21.55%)	83	0/10 (0.00%)	0
INJECTION SITE ERYTHEMA † 1	10/144 (6.94%)	11	17/283 (6.01%)	19	1/10 (10.00%)	1
INJECTION SITE REACTION † 1	11/144 (7.64%)	14	13/283 (4.59%)	24	4/10 (40.00%)	5
INJECTION SITE SWELLING † 1	1/144 (0.69%)	1	0/283 (0.00%)	0	1/10 (10.00%)	1
MALAISE † 1	2/144 (1.39%)	2	15/283 (5.30%)	21	0/10 (0.00%)	0
OEDEMA PERIPHERAL † 1	26/144 (18.06%)	30	70/283 (24.73%)	96	0/10 (0.00%)	0
PAIN † 1	4/144 (2.78%)	6	16/283 (5.65%)	20	0/10 (0.00%)	0
PYREXIA † 1	30/144 (20.83%)	43	66/283 (23.32%)	93	2/10 (20.00%)	5
Hepatobiliary disorders
CHOLECYSTITIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	1/10 (10.00%)	1
HYPERBILIRUBINAEMIA † 1	3/144 (2.08%)	4	9/283 (3.18%)	15	1/10 (10.00%)	2
Immune system disorders
HYPERSENSITIVITY † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
Infections and infestations
ANAL INFECTION † 1	1/144 (0.69%)	1	3/283 (1.06%)	3	1/10 (10.00%)	1
GASTROINTESTINAL FUNGAL INFECTION † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
GINGIVITIS † 1	0/144 (0.00%)	0	3/283 (1.06%)	3	1/10 (10.00%)	1
LUNG INFECTION † 1	1/144 (0.69%)	1	11/283 (3.89%)	11	2/10 (20.00%)	2
ORAL CANDIDIASIS † 1	5/144 (3.47%)	8	17/283 (6.01%)	21	0/10 (0.00%)	0
ORAL HERPES † 1	7/144 (4.86%)	7	17/283 (6.01%)	18	0/10 (0.00%)	0
PERITONITIS † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
PNEUMONIA † 1	8/144 (5.56%)	8	19/283 (6.71%)	19	0/10 (0.00%)	0
RASH PUSTULAR † 1	2/144 (1.39%)	2	4/283 (1.41%)	4	1/10 (10.00%)	1
TINEA INFECTION † 1	1/144 (0.69%)	2	2/283 (0.71%)	3	1/10 (10.00%)	1
UPPER RESPIRATORY TRACT INFECTION † 1	13/144 (9.03%)	15	25/283 (8.83%)	29	4/10 (40.00%)	4
URINARY TRACT INFECTION † 1	7/144 (4.86%)	9	22/283 (7.77%)	34	1/10 (10.00%)	2
Injury, poisoning and procedural complications
BITE † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
CONTUSION † 1	12/144 (8.33%)	13	16/283 (5.65%)	22	0/10 (0.00%)	0
FALL † 1	8/144 (5.56%)	10	33/283 (11.66%)	54	0/10 (0.00%)	0
Investigations
ADENOSINE DEAMINASE INCREASED † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	2/10 (20.00%)	2
ALANINE AMINOTRANSFERASE INCREASED † 1	11/144 (7.64%)	15	24/283 (8.48%)	34	3/10 (30.00%)	3
ASPARTATE AMINOTRANSFERASE INCREASED † 1	12/144 (8.33%)	16	22/283 (7.77%)	31	3/10 (30.00%)	4
BLOOD ALKALINE PHOSPHATASE INCREASED † 1	4/144 (2.78%)	5	15/283 (5.30%)	25	0/10 (0.00%)	0
BLOOD BILIRUBIN INCREASED † 1	5/144 (3.47%)	6	21/283 (7.42%)	28	4/10 (40.00%)	6
BLOOD CREATININE INCREASED † 1	8/144 (5.56%)	13	13/283 (4.59%)	15	2/10 (20.00%)	2
BLOOD LACTATE DEHYDROGENASE INCREASED † 1	2/144 (1.39%)	2	7/283 (2.47%)	8	4/10 (40.00%)	7
C-REACTIVE PROTEIN INCREASED † 1	4/144 (2.78%)	4	16/283 (5.65%)	17	0/10 (0.00%)	0
GAMMA-GLUTAMYLTRANSFERASE INCREASED † 1	2/144 (1.39%)	3	7/283 (2.47%)	11	2/10 (20.00%)	2
NEUTROPHIL COUNT DECREASED † 1	2/144 (1.39%)	2	7/283 (2.47%)	12	1/10 (10.00%)	2
PLATELET COUNT DECREASED † 1	3/144 (2.08%)	9	13/283 (4.59%)	24	1/10 (10.00%)	1
WEIGHT DECREASED † 1	18/144 (12.50%)	22	42/283 (14.84%)	61	4/10 (40.00%)	5
Metabolism and nutrition disorders
DECREASED APPETITE † 1	26/144 (18.06%)	29	78/283 (27.56%)	101	6/10 (60.00%)	7
DIABETES MELLITUS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	1/10 (10.00%)	2
HYPERGLYCAEMIA † 1	6/144 (4.17%)	7	12/283 (4.24%)	14	1/10 (10.00%)	1
HYPERKALAEMIA † 1	3/144 (2.08%)	3	15/283 (5.30%)	16	1/10 (10.00%)	1
HYPERPHOSPHATAEMIA † 1	2/144 (1.39%)	2	9/283 (3.18%)	10	1/10 (10.00%)	1
HYPERURICAEMIA † 1	7/144 (4.86%)	8	8/283 (2.83%)	9	4/10 (40.00%)	5
HYPOALBUMINAEMIA † 1	13/144 (9.03%)	15	23/283 (8.13%)	31	2/10 (20.00%)	5
HYPOCALCAEMIA † 1	9/144 (6.25%)	10	19/283 (6.71%)	27	5/10 (50.00%)	6
HYPOCHLORAEMIA † 1	1/144 (0.69%)	1	2/283 (0.71%)	2	1/10 (10.00%)	1
HYPOKALAEMIA † 1	43/144 (29.86%)	59	84/283 (29.68%)	125	8/10 (80.00%)	13
HYPOMAGNESAEMIA † 1	5/144 (3.47%)	7	24/283 (8.48%)	28	0/10 (0.00%)	0
HYPONATRAEMIA † 1	6/144 (4.17%)	6	16/283 (5.65%)	20	2/10 (20.00%)	2
HYPOPHOSPHATAEMIA † 1	17/144 (11.81%)	23	36/283 (12.72%)	46	2/10 (20.00%)	2
LACTIC ACIDOSIS † 1	1/144 (0.69%)	1	1/283 (0.35%)	1	1/10 (10.00%)	1
TUMOUR LYSIS SYNDROME † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
Musculoskeletal and connective tissue disorders
ARTHRALGIA † 1	7/144 (4.86%)	7	35/283 (12.37%)	43	3/10 (30.00%)	3
ARTHRITIS † 1	2/144 (1.39%)	2	8/283 (2.83%)	9	1/10 (10.00%)	1
BACK PAIN † 1	12/144 (8.33%)	14	25/283 (8.83%)	32	0/10 (0.00%)	0
JOINT SWELLING † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	1/10 (10.00%)	1
MUSCULOSKELETAL PAIN † 1	5/144 (3.47%)	5	18/283 (6.36%)	19	0/10 (0.00%)	0
OSTEOARTHRITIS † 1	2/144 (1.39%)	2	6/283 (2.12%)	6	1/10 (10.00%)	1
PAIN IN EXTREMITY † 1	15/144 (10.42%)	19	23/283 (8.13%)	27	0/10 (0.00%)	0
SPINAL OSTEOARTHRITIS † 1	0/144 (0.00%)	0	2/283 (0.71%)	2	1/10 (10.00%)	1
Nervous system disorders
DIZZINESS † 1	11/144 (7.64%)	14	37/283 (13.07%)	51	1/10 (10.00%)	1
DYSGEUSIA † 1	4/144 (2.78%)	4	11/283 (3.89%)	13	1/10 (10.00%)	1
HEADACHE † 1	12/144 (8.33%)	13	34/283 (12.01%)	38	1/10 (10.00%)	2
PARAESTHESIA † 1	2/144 (1.39%)	2	8/283 (2.83%)	10	1/10 (10.00%)	1
POOR QUALITY SLEEP † 1	4/144 (2.78%)	5	0/283 (0.00%)	0	2/10 (20.00%)	2
Psychiatric disorders
INSOMNIA † 1	15/144 (10.42%)	17	36/283 (12.72%)	39	3/10 (30.00%)	4
Renal and urinary disorders
ACUTE KIDNEY INJURY † 1	8/144 (5.56%)	10	21/283 (7.42%)	27	0/10 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
COUGH † 1	20/144 (13.89%)	21	36/283 (12.72%)	40	2/10 (20.00%)	2
DYSPNOEA † 1	12/144 (8.33%)	14	37/283 (13.07%)	49	0/10 (0.00%)	0
EPISTAXIS † 1	12/144 (8.33%)	14	24/283 (8.48%)	30	0/10 (0.00%)	0
OROPHARYNGEAL PAIN † 1	6/144 (4.17%)	8	28/283 (9.89%)	38	1/10 (10.00%)	2
PLEURAL EFFUSION † 1	5/144 (3.47%)	5	27/283 (9.54%)	29	0/10 (0.00%)	0
Skin and subcutaneous tissue disorders
DERMATITIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
DRY SKIN † 1	3/144 (2.08%)	3	17/283 (6.01%)	20	1/10 (10.00%)	1
ERYTHEMA † 1	5/144 (3.47%)	6	15/283 (5.30%)	17	0/10 (0.00%)	0
PETECHIAE † 1	8/144 (5.56%)	8	18/283 (6.36%)	19	0/10 (0.00%)	0
PRURIGO † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
PRURITUS † 1	6/144 (4.17%)	7	28/283 (9.89%)	34	0/10 (0.00%)	0
RASH † 1	9/144 (6.25%)	9	31/283 (10.95%)	40	3/10 (30.00%)	3
RASH ERYTHEMATOUS † 1	3/144 (2.08%)	3	2/283 (0.71%)	2	2/10 (20.00%)	2
RASH MACULO-PAPULAR † 1	4/144 (2.78%)	4	24/283 (8.48%)	27	0/10 (0.00%)	0
Vascular disorders
AORTIC ARTERIOSCLEROSIS † 1	0/144 (0.00%)	0	0/283 (0.00%)	0	1/10 (10.00%)	1
ARTERIOSCLEROSIS † 1	0/144 (0.00%)	0	1/283 (0.35%)	1	1/10 (10.00%)	1
HAEMATOMA † 1	9/144 (6.25%)	14	16/283 (5.65%)	21	0/10 (0.00%)	0
HYPERTENSION † 1	12/144 (8.33%)	14	30/283 (10.60%)	32	2/10 (20.00%)	3
HYPOTENSION † 1	7/144 (4.86%)	9	23/283 (8.13%)	31	0/10 (0.00%)	0
1 Term from vocabulary, MedDRA 21.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.

Results Point of Contact

• Name/Title: Global Medical Services
• Organization: AbbVie
• Phone: 800-633-9110
• EMail: abbvieclinicaltrials@abbvie.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Badawi M, Chen X, Marroum P, Suleiman AA, Mensing S, Koenigsdorfer A, Schiele JT, Palenski T, Samineni D, Hoffman D, Menon R, Salem AH. Bioavailability Evaluation of Venetoclax Lower-Strength Tablets and Oral Powder Formulations to Establish Interchangeability with the 100 mg Tablet. Clin Drug Investig. 2022 Aug;42(8):657-668. doi: 10.1007/s40261-022-01172-4. Epub 2022 Jul 13.

Pratz KW, Chai X, Xie J, Yin L, Nie X, Montez M, Iantuono E, Downs L, Ma E. Cost-Effectiveness Analysis of Venetoclax in Combination with Azacitidine Versus Azacitidine Monotherapy in Patients with Acute Myeloid Leukemia Who are Ineligible for Intensive Chemotherapy: From a US Third Party Payer Perspective. Pharmacoeconomics. 2022 Aug;40(8):777-790. doi: 10.1007/s40273-022-01145-7. Epub 2022 Jun 13.

Konopleva M, Thirman MJ, Pratz KW, Garcia JS, Recher C, Pullarkat V, Kantarjian HM, DiNardo CD, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Wei AH. Impact of FLT3 Mutation on Outcomes after Venetoclax and Azacitidine for Patients with Treatment-Naive Acute Myeloid Leukemia. Clin Cancer Res. 2022 Jul 1;28(13):2744-2752. doi: 10.1158/1078-0432.CCR-21-3405.

Pollyea DA, DiNardo CD, Arellano ML, Pigneux A, Fiedler W, Konopleva M, Rizzieri DA, Smith BD, Shinagawa A, Lemoli RM, Dail M, Duan Y, Chyla B, Potluri J, Miller CL, Kantarjian HM. Impact of Venetoclax and Azacitidine in Treatment-Naive Patients with Acute Myeloid Leukemia and IDH1/2 Mutations. Clin Cancer Res. 2022 Jul 1;28(13):2753-2761. doi: 10.1158/1078-0432.CCR-21-3467.

Pratz KW, Jonas BA, Pullarkat V, Recher C, Schuh AC, Thirman MJ, Garcia JS, DiNardo CD, Vorobyev V, Fracchiolla NS, Yeh SP, Jang JH, Ozcan M, Yamamoto K, Illes A, Zhou Y, Dail M, Chyla B, Potluri J, Dohner H. Measurable Residual Disease Response and Prognosis in Treatment-Naive Acute Myeloid Leukemia With Venetoclax and Azacitidine. J Clin Oncol. 2022 Mar 10;40(8):855-865. doi: 10.1200/JCO.21.01546. Epub 2021 Dec 15.

DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, Konopleva M, Dohner H, Letai A, Fenaux P, Koller E, Havelange V, Leber B, Esteve J, Wang J, Pejsa V, Hajek R, Porkka K, Illes A, Lavie D, Lemoli RM, Yamamoto K, Yoon SS, Jang JH, Yeh SP, Turgut M, Hong WJ, Zhou Y, Potluri J, Pratz KW. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020 Aug 13;383(7):617-629. doi: 10.1056/NEJMoa2012971.

• Responsible Party: AbbVie
• ClinicalTrials.gov Identifier: NCT02993523
• Other Study ID Numbers: M15-656; 2016-001466-28 ( EudraCT Number )
• First Submitted: December 13, 2016
• First Posted: December 15, 2016
• Results First Submitted: November 28, 2022
• Results First Posted: January 27, 2023
• Last Update Posted: July 3, 2023