Trial Outcomes & Findings for Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma (NCT NCT01881789)

Last Updated: 2022-11-14

Results Overview

DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. A DLT is defined as any of the following treatment-related events: * Any ≥ Grade 3 nonhematologic toxicity with the following conditions: * ≥ Grade 3 nausea, vomiting, diarrhea, or constipation only if for \> 7 days despite optimal supportive care * Asymptomatic Grade 3 hypophosphatemia, Grade 3 hyperglycemia or toxicity solely due to dexamethasone, ≥ Grade 3 rash attributed to lenalidomide, and Grade 3 fatigue for \< 14 days were not considered DLTs * Grade 4 neutropenia: absolute neutrophil count (ANC) \< 0.5 × 10\^9/L lasting ≥ 7 days, despite myeloid growth factor support * Febrile neutropenia * Grade 4 thrombocytopenia for ≥ 7 days or \< 7 days with ≥ Grade 2 clinically significant bleeding or \< 10,000 platelets requiring platelet transfusion, or Grade ≥ 3 with clinically significant bleeding or requiring platelet transfusion.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

22 participants

Primary outcome timeframe

Cycle 1, 28 days

Results posted on

2022-11-14

Participant Flow

This study was conducted at 17 study centers in the United States. Twenty-two participants were enrolled, however one participant discontinued before being assigned to a treatment cohort. Enrollment was halted during dose-escalation and Phase 2 was not conducted.

In the Phase 1b portion of the study participants were enrolled sequentially using a standard 3 + 3 dose escalation schema. The final planned analysis for efficacy was performed using a data cut-off date of 18 July 2016, at which time 3 participants remained on treatment. The final analysis of safety was conducted after all participants had discontinued treatment (23 September 2019).

Participant milestones

Participant milestones
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Overall Study STARTED	3	7	3	3	2	3
Overall Study COMPLETED	0	0	0	0	0	0
Overall Study NOT COMPLETED	3	7	3	3	2	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Overall Study Withdrawal by Subject	0	2	1	0	1	1
Overall Study Study Terminated by Sponsor	0	0	0	0	0	1
Overall Study Other	3	5	2	3	1	1

Baseline Characteristics

Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.	Total n=21 Participants Total of all reporting groups
Age, Continuous	72.3 years STANDARD_DEVIATION 6.1 • n=5 Participants	68.9 years STANDARD_DEVIATION 8.7 • n=7 Participants	64.7 years STANDARD_DEVIATION 2.5 • n=5 Participants	64.7 years STANDARD_DEVIATION 11.0 • n=4 Participants	60.0 years STANDARD_DEVIATION 5.7 • n=21 Participants	67.7 years STANDARD_DEVIATION 4.2 • n=10 Participants	67.1 years STANDARD_DEVIATION 7.4 • n=115 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=10 Participants	6 Participants n=115 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	3 Participants n=4 Participants	0 Participants n=21 Participants	3 Participants n=10 Participants	15 Participants n=115 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	6 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants	20 Participants n=115 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race/Ethnicity, Customized Black	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race/Ethnicity, Customized White	3 Participants n=5 Participants	5 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	2 Participants n=21 Participants	3 Participants n=10 Participants	18 Participants n=115 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	1 Participants n=115 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 0 (Fully active)	1 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	1 Participants n=4 Participants	1 Participants n=21 Participants	3 Participants n=10 Participants	13 Participants n=115 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 1 (Restricted but ambulatory)	2 Participants n=5 Participants	3 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=10 Participants	8 Participants n=115 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status Grade 2 (Ambulatory but unable to work)	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants

PRIMARY outcome

Timeframe: Cycle 1, 28 days

Population: All enrolled participants who received at least 1 dose of any study treatment

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Number of Participants With Dose-Limiting Toxicities (DLTs)	2 Participants	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively.

Population: Participants who received at least 1 dose of any study treatment

Adverse events (AEs) were graded using NCI-CTCAE (version 4.03) and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. A serious AE is an event that met 1 or more of the following criteria: * Death * Life-threatening experience * Required inpatient hospitalization or prolongation of an existing hospitalization * Resulted in persistent or significant disability/incapacity * A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject * Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above. Treatment-related AEs are those considered related to at least 1 study drug by the investigator.

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Number of Participants With Treatment-emergent Adverse Events (AEs) Any treatment-emergent adverse event (TEAE)	3 Participants	7 Participants	3 Participants	3 Participants	2 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TEAE ≥ grade 3	3 Participants	6 Participants	3 Participants	3 Participants	2 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Serious adverse events	2 Participants	4 Participants	3 Participants	2 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TEAEs leading to discontinuation of study drug	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Fatal adverse events	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Treatment-related adverse events (TRAE)	3 Participants	7 Participants	3 Participants	3 Participants	2 Participants	3 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TRAE ≥ grade 3	3 Participants	6 Participants	2 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) Treatment-related serious adverse events	2 Participants	4 Participants	2 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Treatment-emergent Adverse Events (AEs) TRAEs leading to discontinuation of study drug	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI.

Population: Participants in the 5/14 dosing schedule groups with available concentration data

Plasma samples for oprozomib concentration assays were only collected for participants in the 5/14 dosing schedule groups. Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=4 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Plasma Oprozomib Concentration Cycle 1 day 1, 1 - 2.5 hours post EOI	497 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	632 ng/mL Standard Deviation 657	697 ng/mL Standard Deviation 435	—	—	—
Plasma Oprozomib Concentration Cycle 1 day 1, 2.75 - 5 hours post EOI	299 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	15.8 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	78.0 ng/mL Standard Deviation 48.9	—	—	—
Plasma Oprozomib Concentration Cycle 3 day 1, predose	0.0 ng/mL	142 ng/mL Standard Deviation 285	0.0 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	—	—	—
Plasma Oprozomib Concentration Cycle 3 day 1, 1 - 2.5 hours post EOI	111 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	175 ng/mL Standard Deviation 303	178 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	—	—	—
Plasma Oprozomib Concentration Cycle 3 day 1, 2.75 - 5 hours post EOI	2.00 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	255 ng/mL Standard Deviation 323	69.1 ng/mL Standard Deviation NA Standard deviation not calculated when N ≤ 2	—	—	—

SECONDARY outcome

Timeframe: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively

Population: All participants who received at least 1 dose of any study treatment

ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria. PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to \< 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein \<100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and \<5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM).

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Overall Response Rate (ORR)	66.7 percentage of participants Interval 9.4 to 99.2	57.1 percentage of participants Interval 18.4 to 90.1	66.7 percentage of participants Interval 9.4 to 99.2	100.0 percentage of participants Interval 29.2 to 100.0	50.0 percentage of participants Interval 1.3 to 98.7	100.0 percentage of participants Interval 29.2 to 100.0

SECONDARY outcome

Timeframe: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively.

Population: Participants who received at least 1 dose of any study treatment and who achieved a best overall response of sCR, CR, VGPR, or PR.

Duration of response was defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause. Median DOR was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=4 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=1 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Duration of Response (DOR)	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events

SECONDARY outcome

Timeframe: From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively

Population: All participants who received at least 1 dose of any study treatment.

Progression-free survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever occurred first. Median PFS was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.

Outcome measures

Outcome measures
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 Participants Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 Participants Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 Participants Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Progression-Free Survival (PFS)	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events	NA months Could not be estimated due to the low number of events

Adverse Events

Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone

Serious events: 4 serious events

Other events: 7 other events

Deaths: 0 deaths

Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone

Serious events: 2 serious events

Other events: 3 other events

Deaths: 0 deaths

Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 participants at risk Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 participants at risk Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Blood and lymphatic system disorders Anaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Febrile neutropenia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Cardiac disorders Bradycardia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Cardiac disorders Myocardial infarction	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Diarrhoea	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Nausea	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Pancreatitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Upper gastrointestinal haemorrhage	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Disease progression	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Bacterial sepsis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Bronchitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Cellulitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Gastroenteritis viral	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Lung infection	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Neutropenic infection	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Neutropenic sepsis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Pneumonia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Sepsis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Urinary tract infection	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Fall	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Laceration	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Electrocardiogram QT prolonged	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Platelet count decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypophosphataemia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Myoclonus	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Syncope	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Renal failure	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Capillary leak syndrome	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Deep vein thrombosis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Hypotension	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.

Other adverse events

Other adverse events
Measure	Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone n=7 participants at risk Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first.	Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone n=2 participants at risk Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment.	Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone n=3 participants at risk Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment.
Investigations Neutrophil count decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Neutrophil count increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Protein total decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Anaemia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Leukopenia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Lymphopenia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Neutropenia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Blood and lymphatic system disorders Thrombocytopenia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	28.6% 2/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Cardiac disorders Bradycardia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Cardiac disorders Palpitations	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Cardiac disorders Tachycardia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Ear and labyrinth disorders Ear pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Eye disorders Dry eye	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Eye disorders Vision blurred	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Abdominal distension	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	28.6% 2/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Abdominal pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Cheilitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Constipation	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	57.1% 4/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Diarrhoea	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	71.4% 5/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Dry mouth	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Dyspepsia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Faecaloma	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Flatulence	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Gastrointestinal toxicity	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Haemorrhoids	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Melaena	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Nausea	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	85.7% 6/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 2/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Stomatitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Gastrointestinal disorders Vomiting	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	42.9% 3/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Asthenia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	28.6% 2/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Chills	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Fatigue	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	57.1% 4/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Gait disturbance	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Non-cardiac chest pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Oedema	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Oedema peripheral	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Peripheral swelling	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Pyrexia	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Thirst	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
General disorders Xerosis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Bronchitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Candida infection	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Cellulitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Folliculitis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Herpes zoster	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Nasopharyngitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Pharyngitis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Pneumonia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Sinusitis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Skin infection	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Tinea infection	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Upper respiratory tract infection	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Urinary tract infection	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Infections and infestations Viral infection	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Compression fracture	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Contusion	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Fall	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Lumbar vertebral fracture	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Injury, poisoning and procedural complications Wound	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Alanine aminotransferase increased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Aspartate aminotransferase decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Aspartate aminotransferase increased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood alkaline phosphatase decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood alkaline phosphatase increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood bicarbonate decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood bilirubin increased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood chloride increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood creatinine increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood lactate dehydrogenase decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood lactate dehydrogenase increased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood phosphorus increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood pressure increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood urea increased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Blood uric acid decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Carbon dioxide increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Lymphocyte count decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Red blood cell count decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations Weight decreased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations White blood cell count decreased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Investigations White blood cell count increased	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Appetite disorder	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	42.9% 3/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Dehydration	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hyperglycaemia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypermagnesaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypokalaemia	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	28.6% 2/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypomagnesaemia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Metabolism and nutrition disorders Hypophosphataemia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Arthralgia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Back pain	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Bone pain	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Coccydynia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Joint range of motion decreased	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Muscular weakness	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Myalgia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Neck pain	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Musculoskeletal and connective tissue disorders Pain in extremity	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Polycythaemia vera	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Seborrhoeic keratosis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Burning sensation	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Dizziness	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	57.1% 4/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Dizziness postural	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Dysgeusia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Headache	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Hypoaesthesia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Memory impairment	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Neuropathy peripheral	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Paraesthesia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Presyncope	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Nervous system disorders Tremor	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Claustrophobia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Confusional state	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Depressed mood	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Insomnia	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Irritability	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Psychiatric disorders Sleep disorder	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Dysuria	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Pollakiuria	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Polyuria	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Renal failure	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Renal and urinary disorders Urinary retention	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Reproductive system and breast disorders Genital rash	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Cough	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 2/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	100.0% 3/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Dyspnoea	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	28.6% 2/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Productive cough	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	66.7% 2/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Sinus congestion	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Tachypnoea	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Acne	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Blister	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Ecchymosis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Rash	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Aortic arteriosclerosis	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Hot flush	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Hypertension	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	50.0% 1/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Hypotension	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	14.3% 1/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.
Vascular disorders Orthostatic hypotension	33.3% 1/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/7 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/2 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.	0.00% 0/3 • From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively.

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER