Trial Outcomes & Findings for Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia (NCT NCT02920008)

NCT ID: NCT02920008

Last Updated: 2024-08-28

Results Overview

Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 302 participants
• Primary outcome timeframe: From the date of randomization until the date of death, or approximately 34 months
• Results posted on: 2024-08-28

Participant Flow

A total of 358 participants were assessed for study inclusion. Of these 56 failed screening assessments. A total of 302 participants were randomized (148 guadecitabine, 154 treatment choice [TC]). Of the randomized participants, 10 did not receive study drug (3 guadecitabine, 7 TC).

Participant milestones

Measure	Guadecitabine Guadecitabine was administered subcutaneously (SC) at a dose of 60 milligrams per meter square (mg/m\^2) for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) Intermediate or high dose cytarabine (HiDAC), mitoxantrone, etoposide and cytarabine (MEC) and granulocyte colony-stimulating factors (G-CSF)/fludarabine, cytarabine, G-CSF and idarubicin (FLAG/FLAG-Ida), low dose cytarabine (LDAC), decitabine, azacitidine, or best supportive care (BSC) was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 grams per meter square (g/m\^2) every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 intravenous (IV) (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Overall Study STARTED	148	154
Overall Study Safety Analysis Set	145	147
Overall Study COMPLETED	28	20
Overall Study NOT COMPLETED	120	134

Reasons for withdrawal

Measure	Guadecitabine Guadecitabine was administered subcutaneously (SC) at a dose of 60 milligrams per meter square (mg/m\^2) for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) Intermediate or high dose cytarabine (HiDAC), mitoxantrone, etoposide and cytarabine (MEC) and granulocyte colony-stimulating factors (G-CSF)/fludarabine, cytarabine, G-CSF and idarubicin (FLAG/FLAG-Ida), low dose cytarabine (LDAC), decitabine, azacitidine, or best supportive care (BSC) was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 grams per meter square (g/m\^2) every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 intravenous (IV) (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Overall Study Death	117	127
Overall Study Withdrawal by Subject	3	6
Overall Study Lost to Follow-up	0	1

Baseline Characteristics

Phase 3 Randomized, Open-Label Study of Guadecitabine vs Treatment Choice in Previously Treated Acute Myeloid Leukemia

Baseline characteristics by cohort

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.	Total n=302 Participants Total of all reporting groups
Age, Continuous	61.8 years STANDARD_DEVIATION 12.2 • n=5 Participants	59.8 years STANDARD_DEVIATION 13.1 • n=7 Participants	60.8 years STANDARD_DEVIATION 12.7 • n=5 Participants
Sex: Female, Male Female	62 Participants n=5 Participants	76 Participants n=7 Participants	138 Participants n=5 Participants
Sex: Female, Male Male	86 Participants n=5 Participants	78 Participants n=7 Participants	164 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	18 Participants n=5 Participants	16 Participants n=7 Participants	34 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	113 Participants n=5 Participants	114 Participants n=7 Participants	227 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	24 Participants n=7 Participants	41 Participants n=5 Participants
Race/Ethnicity, Customized White	95 Participants n=5 Participants	90 Participants n=7 Participants	185 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	30 Participants n=5 Participants	34 Participants n=7 Participants	64 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	19 Participants n=5 Participants	24 Participants n=7 Participants	43 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization until the date of death, or approximately 34 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Overall survival is defined as number of days from day of randomization to date of death, regardless of cause.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Overall Survival	191.0 days Interval 141.0 to 253.0	163.0 days Interval 131.0 to 213.0

SECONDARY outcome

Timeframe: From the date of randomization until the date of death, or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Event-free survival is defined as number of days from randomization to earliest date of treatment discontinuation (for reasons other than initiation of hematopoietic cell transplant [HCT]), start of alternative anti-leukemia therapy (except HCT), or death.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Event-Free Survival	90.0 days Interval 73.0 to 105.0	71.5 days Interval 53.0 to 78.0

SECONDARY outcome

Timeframe: Up to approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Survival rate at 1 year after randomization; participants were also followed to estimate 2-year survival rate.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Long-Term Survival 12-month survival rate	0.32 proportion Interval 0.25 to 0.4	0.26 proportion Interval 0.2 to 0.34
Long-Term Survival 24-month survival rate	0.19 proportion Interval 0.12 to 0.26	0.10 proportion Interval 0.05 to 0.17

SECONDARY outcome

Timeframe: 6 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Number of days participants alive and out of hospital during first 6 months of the study.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Number of Days Alive and Out of the Hospital (NDAOH)	73.2 days Interval 53.2 to 93.2	73.9 days Interval 53.8 to 94.1

SECONDARY outcome

Timeframe: Baseline up to approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Number of participants without red blood cells (RBC) or platelet transfusion for any 8-week period after treatment divided by total number of participants in efficacy analysis.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Transfusion Independence Rate Overall transfusion independence	20.3 percentage of participants	13.0 percentage of participants
Transfusion Independence Rate Platelet transfusion independence	23.6 percentage of participants	21.4 percentage of participants
Transfusion Independence Rate RBC transfusion independence	21.6 percentage of participants	14.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to end of treatment, or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

The Complete response (CR) rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as the number of participants with a best response of CR divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Complete Response Rate	12.8 percentage of participants	7.1 percentage of participants

SECONDARY outcome

Timeframe: Baseline to end of treatment, or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

The combined CR and CR with partial hematologic recovery rate based on modified International Working Group (IWG) 2003 AML Response Criteria was calculated as number of participants with CR and CR with partial hematologic recovery divided by the total number of participants included in the efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is absolute neutrophil count (ANC) ≥1000/μL, platelets ≥100,000/μL, independence from red blood cells (RBC) and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Combined Complete Response and Complete Response With Partial Hematologic Recovery Rate	16.9 percentage of participants	7.8 percentage of participants

SECONDARY outcome

Timeframe: Baseline to end of treatment, or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Composite complete response rate based on modified IWG 2003 AML Response Criteria defined as number of participants with best response of CR, CR with incomplete platelet recovery (CRp), or CR with incomplete blood count recovery (CRi) divided by total number of participants in efficacy analysis. CR as per modified 2003 IWG AML Response Criteria is ANC ≥1000/μL, platelets ≥100,000/μL, independence from RBC and platelet transfusions over the past week, no leukemic blasts in peripheral blood and bone marrow should contain less than 5% blast cells. CRp is defined as ANC ≥1000/μL, Platelets <100,000/μL, independence from RBC transfusions over the past week, no leukemic blasts and bone marrow should contain less than 5% blast cells. CRi is defined as ANC <1000/μL, no leukemic blasts and bone marrow should contain less than 5% blast cells.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Composite Complete Response Rate	27.0 percentage of participants	14.3 percentage of participants

SECONDARY outcome

Timeframe: Baseline to long term follow-up or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

Number of participants who received HCT after randomization divided by total number of participants in efficacy analysis.

Outcome measures

Measure	Guadecitabine n=148 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=154 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Hematopoietic Cell Transplant (HCT) Rate	17.6 percentage of participants	16.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline to end of treatment, or approximately 38 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

The time from first CR or CRh to time of relapse (the date of the earliest of the following 3 events):

1. relapse (defined as the earliest time point whereby BM assessment or PB assessment by the investigator indicate relapse/disease progression due to confirmed reappearance of leukemic blasts in PB or ≥5% leukemic blasts in BM, or clinical progression determined by the investigator),

2. start of alternative therapy (except HCT) or

3. death.

Outcome measures

Measure	Guadecitabine n=25 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=12 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Duration of Complete Response (CR) + CR With Partial Hematologic Recovery (CRh)	124 days Interval 73.0 to 315.0	63 days Interval 8.0 to 71.0

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment. Overall number of participants analyzed is the number of participants with data available for analysis in this outcome measure.

Index score is calculated based on 5-level version of the EQ-5D descriptive system using the value set for England.

The range of index score is from -0.281 (for the worst health state, score of 5 for all categories) to 1 (for the best health state, score of 1 for all categories).

Outcome measures

Measure	Guadecitabine n=107 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=102 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 2 Day 1	-0.027 score on a scale Interval -0.061 to 0.007	-0.034 score on a scale Interval -0.068 to 0.001
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 3 Day 1	-0.026 score on a scale Interval -0.063 to 0.011	-0.028 score on a scale Interval -0.066 to 0.01
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 4 Day 1	-0.008 score on a scale Interval -0.05 to 0.034	-0.061 score on a scale Interval -0.108 to -0.015
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 5 Day 1	-0.022 score on a scale Interval -0.072 to 0.027	-0.072 score on a scale Interval -0.126 to -0.019
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 6 Day 1	-0.027 score on a scale Interval -0.071 to 0.017	-0.070 score on a scale Interval -0.188 to -0.022
Change From Baseline in EuroQoL-5 Dimension 5 Level (EQ-5D-5L) Index Scores Cycle 7 Day 1	-0.020 score on a scale Interval -0.071 to 0.03	-0.022 score on a scale Interval -0.076 to 0.033

SECONDARY outcome

Timeframe: Baseline to 6 months

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment. Overall number of participants analyzed is the number of participants with data available for analysis in this outcome measure.

VAS score is obtained using vertical 20-cm visual analogue scale with the top value of 100 labelled as 'the best health you can imagine' and the bottom value of 0 labelled as 'the worst health you can imagine'.

Outcome measures

Measure	Guadecitabine n=107 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=102 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 7 Day 1	-0.44 score on a scale Interval -5.66 to 4.78	-0.77 score on a scale Interval -6.46 to 4.93
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 2 Day 1	-2.80 score on a scale Interval -6.26 to 0.65	-1.86 score on a scale Interval -5.4 to 1.67
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 3 Day 1	-0.61 score on a scale Interval -4.08 to 2.87	-1.47 score on a scale Interval -5.02 to 2.08
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 4 Day 1	1.13 score on a scale Interval -2.24 to 4.51	-2.37 score on a scale Interval -6.04 to 1.29
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 5 Day 1	1.28 score on a scale Interval -2.88 to 5.44	-2.30 score on a scale Interval -6.83 to 2.22
Change in EQ-5D-5L Visual Analogue Scale (VAS) Score Cycle 6 Day 1	0.67 score on a scale Interval -3.51 to 4.85	-1.42 score on a scale Interval -6.04 to 3.21

SECONDARY outcome

Timeframe: From first dose until 30 days after the last dose of study drug, or approximately 38 months

Population: The safety analysis set included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

An AE is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including a clinically significant abnormal finding in laboratory tests or other diagnostic procedures), symptom, or disease temporally associated with the use of a drug, without any judgment about causality.

Outcome measures

Measure	Guadecitabine n=145 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=147 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Percentage of Participants With Adverse Events (AEs)	96.6 percentage of participants	97.3 percentage of participants

SECONDARY outcome

Timeframe: From the first dose until 60 days after the first dose of study drug

Population: The efficacy analysis set included data from all participants randomly assigned to study treatment.

All-cause mortality in the first 30 days and first 60 days after the start of treatment divided by the total number of participants receiving at least one dose of study treatment.

Outcome measures

Measure	Guadecitabine n=145 Participants Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=147 Participants Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
All-Cause Mortality Within 30 days	11.7 percentage of participants	9.5 percentage of participants
All-Cause Mortality Within 60 days	24.8 percentage of participants	20.4 percentage of participants

Adverse Events

Guadecitabine

Serious events: 113 serious events

Other events: 138 other events

Deaths: 117 deaths

Treatment Choice (TC)

Serious events: 91 serious events

Other events: 137 other events

Deaths: 129 deaths

Serious adverse events

Measure	Guadecitabine n=145 participants at risk Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=147 participants at risk Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Vascular disorders Embolism	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Vascular disorders Hypotension	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Vascular disorders Venous thrombosis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Meningioma	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour associated fever	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Asthenia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders General physical health deterioration	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Multiple organ dysfunction syndrome	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Oedema peripheral	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Pyrexia	3.4% 5/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.1% 6/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Psychiatric disorders Suicidal ideation	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Anaphylactic transfusion reaction	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Contusion	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Ilium fracture	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Postoperative respiratory distress	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Transfusion reaction	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Alanine aminotransferase increased	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Aspartate aminotransferase increased	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations C-reactive protein increased	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Electrocardiogram QT prolonged	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Gamma-glutamyltransferase increased	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Troponin T increased	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Acute myocardial infarction	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Atrial fibrillation	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardiac arrest	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardiac failure	2.1% 3/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardiac failure acute	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardiac failure chronic	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardiac failure congestive	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Cardio-respiratory arrest	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Myocardial infarction	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Cardiac disorders Pericardial effusion	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Congenital, familial and genetic disorders Aplasia	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Acute pulmonary oedema	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Acute respiratory distress syndrome	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.1% 3/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Lung disorder	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Lung infiltration	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Respiratory distress	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Anaemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Bone marrow failure	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Febrile bone marrow aplasia	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.0% 3/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Febrile neutropenia	28.3% 41/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	22.4% 33/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Neutropenia	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Thrombocytopenia	2.1% 3/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Brain stem infarction	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Cerebral haemorrhage	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Cerebral ischaemia	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Haemorrhage intracranial	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Hydrocephalus	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Peripheral motor neuropathy	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Peripheral sensory neuropathy	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Sciatica	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Ear and labyrinth disorders Deafness unilateral	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Colitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Constipation	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Diarrhoea	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Haemorrhoids	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Ileus	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Large intestine perforation	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Lower gastrointestinal haemorrhage	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Mouth haemorrhage	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Neutropenic colitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Oesophageal mucosal tear	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Oesophagitis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Oral mucosal erythema	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Rectal haemorrhage	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Salivary gland enlargement	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Stomatitis	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Tongue oedema	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Renal and urinary disorders Acute kidney injury	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Renal and urinary disorders Haematuria	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Renal and urinary disorders Renal colic	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Renal and urinary disorders Renal failure	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Hepatobiliary disorders Cholecystitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Skin and subcutaneous tissue disorders Drug reaction with eosinophilia and systemic symptoms	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Skin and subcutaneous tissue disorders Skin ulcer	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Arthritis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Rotator cuff syndrome	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Abdominal infection	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Anal abscess	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Anal infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Anorectal infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Arthritis bacterial	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Aspergillus infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Bacteraemia	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Bartholinitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Bronchopulmonary aspergillosis	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Cellulitis	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Clostridium difficile colitis	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Corynebacterium bacteraemia	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Cystitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Dermo-hypodermitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Device related infection	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.0% 3/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Disseminated varicella zoster vaccine virus infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Diverticulitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Ecthyma	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Endocarditis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Enteritis infectious	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Enterobacter infection	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Enterococcal bacteraemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations External ear cellulitis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Fungal infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Gastroenteritis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Genital infection	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Groin abscess	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Herpes simplex	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Infective myositis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Influenza	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Intestinal sepsis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Klebsiella bacteraemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Liver abscess	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Mucormycosis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Necrotising fasciitis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Neutropenic infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Oral infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Otitis media	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Parvovirus B19 infection	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Perineal abscess	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Periorbital cellulitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Pharyngitis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Pneumocystis jirovecii pneumonia	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Pneumonia	18.6% 27/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	17.0% 25/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Pseudomonal bacteraemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Respiratory tract infection	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Respiratory tract infection viral	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Sepsis	10.3% 15/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	10.9% 16/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Septic shock	4.8% 7/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Sinusitis fungal	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Soft tissue infection	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.0% 3/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Staphylococcal bacteraemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Staphylococcal sepsis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Streptococcal bacteraemia	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Streptococcal sepsis	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Subcutaneous abscess	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Tooth abscess	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Upper respiratory tract infection	0.00% 0/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Urinary tract infection	1.4% 2/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.68% 1/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Urosepsis	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	0.00% 0/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Escherichia bacteraemia	0.69% 1/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

Other adverse events

Measure	Guadecitabine n=145 participants at risk Guadecitabine was administered SC at a dose of 60 mg/m\^2 for 10 days on Days 1-5 and Days 8-12 or on Days 1-10 in the first cycle. Second cycle was 60 mg/m\^2 for either 10 days (Days 1-5 and 8-12 or Days 1-10) or 5 days (Days 1-5 only) based on assessment of disease response, and hematological recovery by end of Cycle 1. For Cycles ≥3, guadecitabine, 60 mg/m\^2 was given for 5 days only (Days 1-5). Each cycle = 28 days.	Treatment Choice (TC) n=147 participants at risk Intermediate or HiDAC, MEC, and FLAG/FLAG-Ida, LDAC, decitabine, azacitidine, or BSC was administered only. High intensity: Intermediate or HiDAC, recommended as 1-1.5 g/m\^2 every 12 hours or up to 6 g/m\^2/day for ≤6 days, maximum 36 g/m\^2 per cycle; MEC: For example: mitoxantrone 6-12 mg/m\^2 IV (recommended 8 mg/m\^2), etoposide 80-200 mg/m\^2 IV (recommended 100 mg/m\^2), and cytarabine 1000 mg/m\^2 IV; each daily for 5 days (Days 1-5); FLAG/FLAG-Ida: For example: fludarabine 25-30 mg/m\^2 IV daily Days 1-5; cytarabine 1-2 g/m\^2 IV daily for up to 5 days (recommended to be given for 4 hours after fludarabine); G-CSF SC daily from Day 6 up to white cell count recovery with or without idarubicin 8 mg/m\^2 IV daily on Days 3 to 5. Low intensity: LDAC 20 mg SC or IV twice daily on Days 1-10; Decitabine 20 mg/m\^2 IV daily on Days 1-5; Azacitidine 75 mg/m\^2 IV or SC daily on Days 1-7. Best supportive care only.
Vascular disorders Hypertension	10.3% 15/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.7% 4/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Vascular disorders Hypotension	13.1% 19/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	7.5% 11/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Asthenia	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	10.2% 15/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Fatigue	13.8% 20/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	18.4% 27/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Injection site reaction	20.0% 29/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	8.2% 12/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Oedema peripheral	15.9% 23/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	15.6% 23/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
General disorders Pyrexia	22.8% 33/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	24.5% 36/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Psychiatric disorders Insomnia	9.7% 14/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	8.8% 13/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Injury, poisoning and procedural complications Contusion	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.1% 6/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Alanine aminotransferase increased	8.3% 12/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.8% 7/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Aspartate aminotransferase increased	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	5.4% 8/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Blood alkaline phosphatase increased	4.1% 6/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	5.4% 8/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Blood bilirubin increased	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Blood creatinine increased	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.7% 4/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Investigations Weight decreased	3.4% 5/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Anaemia	25.5% 37/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	27.9% 41/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Febrile neutropenia	17.2% 25/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	19.7% 29/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Leukopenia	9.7% 14/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	9.5% 14/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Neutropenia	32.4% 47/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	19.0% 28/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Blood and lymphatic system disorders Thrombocytopenia	29.7% 43/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	31.3% 46/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Cough	15.2% 22/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	18.4% 27/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Dyspnoea	13.8% 20/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	11.6% 17/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Epistaxis	11.0% 16/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	10.9% 16/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.8% 4/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Dizziness	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	7.5% 11/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Nervous system disorders Headache	20.7% 30/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	13.6% 20/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Abdominal pain	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	7.5% 11/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Constipation	22.8% 33/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	22.4% 33/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Diarrhoea	24.8% 36/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	21.8% 32/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Dyspepsia	8.3% 12/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Haemorrhoids	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Nausea	29.0% 42/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	25.9% 38/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Stomatitis	11.0% 16/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	13.6% 20/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Gastrointestinal disorders Vomiting	16.6% 24/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	13.6% 20/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Renal and urinary disorders Dysuria	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	1.4% 2/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Skin and subcutaneous tissue disorders Petechiae	8.3% 12/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.8% 7/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Skin and subcutaneous tissue disorders Rash	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Arthralgia	8.3% 12/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.8% 10/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Back pain	10.3% 15/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	8.2% 12/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Myalgia	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Musculoskeletal and connective tissue disorders Pain in extremity	7.6% 11/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.8% 7/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Decreased appetite	18.6% 27/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	13.6% 20/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hyperkalaemia	6.2% 9/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.0% 3/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypoalbuminaemia	6.9% 10/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	4.8% 7/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypocalcaemia	6.2% 9/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypokalaemia	20.0% 29/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	25.9% 38/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypomagnesaemia	9.7% 14/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	10.9% 16/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hyponatraemia	6.9% 10/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	2.0% 3/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Metabolism and nutrition disorders Hypophosphataemia	9.0% 13/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	6.1% 9/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Oral herpes	5.5% 8/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	3.4% 5/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.
Infections and infestations Pneumonia	10.3% 15/145 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.	9.5% 14/147 • From first dose until 30 days after the last dose of study drug, or approximately 38 months All-cause mortality is reported for enrolled participants in the study. The serious and other adverse events is reported for safety analysis set which included data from all participants randomly assigned to study treatment who received any amount of study treatment or any component of a multi-dose study treatment regimen.

Additional Information

Taiho Central

Taiho Oncology, Inc.

Phone: 609-250-7336

Email: clinicaltrialinfo@taihooncology.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place