Trial Outcomes & Findings for A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer (NCT NCT03748641)

Last Updated: 2025-11-13

Results Overview

As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by computerized tomography (CT) or magnetic resonance imaging (MRI) as per response evaluation criteria in solid tumors (RECIST) 1.1; (2) Progression of bone lesions observed by bone scan based on prostate cancer working group 3 (PCWG3) criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan greater than or equal to (\>=) 6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan less than (\<) 2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.

Recruitment status

ACTIVE_NOT_RECRUITING

Study phase

PHASE3

Target enrollment

765 participants

Primary outcome timeframe

Up to 32 months

Results posted on

2025-11-13

Participant Flow

Participant milestones

Participant milestones
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and negative HRR gene alteration, received niraparib 200 mg capsule in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and negative HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg Participants with mCRPC and positive HRR gene alteration, received fixed-dose combination (FDC) of niraparib 200 mg and abiraterone acetate 1000 mg combination tablet orally QD with prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 9 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive same treatment in long-term extension phase.
Overall Study STARTED	212	211	123	124	95
Overall Study Breast Cancer Gene (BRCA) Subgroup	113	112	0	0	52
Overall Study COMPLETED	0	0	0	0	0
Overall Study NOT COMPLETED	212	211	123	124	95

Reasons for withdrawal

Reasons for withdrawal
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and negative HRR gene alteration, received niraparib 200 mg capsule in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg Participants with mCRPC and negative HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg Participants with mCRPC and positive HRR gene alteration, received fixed-dose combination (FDC) of niraparib 200 mg and abiraterone acetate 1000 mg combination tablet orally QD with prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 9 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive same treatment in long-term extension phase.
Overall Study Ongoing	155	148	66	79	84
Overall Study Death	54	59	51	42	9
Overall Study Lost to Follow-up	0	2	1	0	0
Overall Study Withdrawal by Subject	3	2	5	3	2

Baseline Characteristics

A Study of Niraparib in Combination With Abiraterone Acetate and Prednisone Versus Abiraterone Acetate and Prednisone for Treatment of Participants With Metastatic Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=212 Participants Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=211 Participants Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=123 Participants Participants with mCRPC and negative HRR gene alteration, received niraparib 200 mg capsule in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=124 Participants Participants with mCRPC and negative HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg n=95 Participants Participants with mCRPC and positive HRR gene alteration, received fixed-dose combination (FDC) of niraparib 200 mg and abiraterone acetate 1000 mg combination tablet orally QD with prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 9 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive same treatment in long-term extension phase.	Total n=765 Participants Total of all reporting groups
Age, Continuous	69.2 years STANDARD_DEVIATION 8.79 • n=10 Participants	68.6 years STANDARD_DEVIATION 8.17 • n=10 Participants	71.2 years STANDARD_DEVIATION 7.11 • n=20 Participants	71.1 years STANDARD_DEVIATION 7.52 • n=45 Participants	69.2 years STANDARD_DEVIATION 8.99 • n=44 Participants	69.7 years STANDARD_DEVIATION 8.25 • n=8 Participants
Sex: Female, Male Female	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	0 Participants n=8 Participants
Sex: Female, Male Male	212 Participants n=10 Participants	211 Participants n=10 Participants	123 Participants n=20 Participants	124 Participants n=45 Participants	95 Participants n=44 Participants	765 Participants n=8 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	26 Participants n=10 Participants	25 Participants n=10 Participants	8 Participants n=20 Participants	12 Participants n=45 Participants	12 Participants n=44 Participants	83 Participants n=8 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	166 Participants n=10 Participants	169 Participants n=10 Participants	110 Participants n=20 Participants	105 Participants n=45 Participants	77 Participants n=44 Participants	627 Participants n=8 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	20 Participants n=10 Participants	17 Participants n=10 Participants	5 Participants n=20 Participants	7 Participants n=45 Participants	6 Participants n=44 Participants	55 Participants n=8 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	1 Participants n=44 Participants	3 Participants n=8 Participants
Race (NIH/OMB) Asian	29 Participants n=10 Participants	41 Participants n=10 Participants	45 Participants n=20 Participants	37 Participants n=45 Participants	14 Participants n=44 Participants	166 Participants n=8 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=10 Participants	0 Participants n=10 Participants	1 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	1 Participants n=8 Participants
Race (NIH/OMB) Black or African American	5 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants	8 Participants n=8 Participants
Race (NIH/OMB) White	160 Participants n=10 Participants	153 Participants n=10 Participants	72 Participants n=20 Participants	83 Participants n=45 Participants	70 Participants n=44 Participants	538 Participants n=8 Participants
Race (NIH/OMB) More than one race	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	0 Participants n=8 Participants
Race (NIH/OMB) Unknown or Not Reported	17 Participants n=10 Participants	16 Participants n=10 Participants	5 Participants n=20 Participants	4 Participants n=45 Participants	7 Participants n=44 Participants	49 Participants n=8 Participants
Region of Enrollment ARGENTINA	2 Participants n=10 Participants	5 Participants n=10 Participants	2 Participants n=20 Participants	7 Participants n=45 Participants	2 Participants n=44 Participants	18 Participants n=8 Participants
Region of Enrollment AUSTRALIA	15 Participants n=10 Participants	12 Participants n=10 Participants	12 Participants n=20 Participants	9 Participants n=45 Participants	3 Participants n=44 Participants	51 Participants n=8 Participants
Region of Enrollment BELGIUM	5 Participants n=10 Participants	1 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants	0 Participants n=44 Participants	11 Participants n=8 Participants
Region of Enrollment BRAZIL	20 Participants n=10 Participants	14 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	10 Participants n=44 Participants	44 Participants n=8 Participants
Region of Enrollment BULGARIA	1 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	1 Participants n=8 Participants
Region of Enrollment CANADA	4 Participants n=10 Participants	7 Participants n=10 Participants	1 Participants n=20 Participants	4 Participants n=45 Participants	3 Participants n=44 Participants	19 Participants n=8 Participants
Region of Enrollment CHINA	7 Participants n=10 Participants	4 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	11 Participants n=8 Participants
Region of Enrollment CZECH REPUBLIC	4 Participants n=10 Participants	3 Participants n=10 Participants	1 Participants n=20 Participants	2 Participants n=45 Participants	1 Participants n=44 Participants	11 Participants n=8 Participants
Region of Enrollment FRANCE	13 Participants n=10 Participants	12 Participants n=10 Participants	5 Participants n=20 Participants	4 Participants n=45 Participants	3 Participants n=44 Participants	37 Participants n=8 Participants
Region of Enrollment GERMANY	0 Participants n=10 Participants	4 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	5 Participants n=44 Participants	9 Participants n=8 Participants
Region of Enrollment HUNGARY	7 Participants n=10 Participants	4 Participants n=10 Participants	3 Participants n=20 Participants	2 Participants n=45 Participants	1 Participants n=44 Participants	17 Participants n=8 Participants
Region of Enrollment ISRAEL	0 Participants n=10 Participants	0 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants	3 Participants n=8 Participants
Region of Enrollment ITALY	9 Participants n=10 Participants	10 Participants n=10 Participants	3 Participants n=20 Participants	3 Participants n=45 Participants	11 Participants n=44 Participants	36 Participants n=8 Participants
Region of Enrollment MALAYSIA	5 Participants n=10 Participants	10 Participants n=10 Participants	17 Participants n=20 Participants	7 Participants n=45 Participants	1 Participants n=44 Participants	40 Participants n=8 Participants
Region of Enrollment MEXICO	3 Participants n=10 Participants	2 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	0 Participants n=44 Participants	5 Participants n=8 Participants
Region of Enrollment NETHERLANDS	3 Participants n=10 Participants	4 Participants n=10 Participants	2 Participants n=20 Participants	2 Participants n=45 Participants	0 Participants n=44 Participants	11 Participants n=8 Participants
Region of Enrollment POLAND	12 Participants n=10 Participants	12 Participants n=10 Participants	11 Participants n=20 Participants	15 Participants n=45 Participants	4 Participants n=44 Participants	54 Participants n=8 Participants
Region of Enrollment PORTUGAL	1 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	0 Participants n=45 Participants	3 Participants n=44 Participants	5 Participants n=8 Participants
Region of Enrollment RUSSIAN FEDERATION	19 Participants n=10 Participants	21 Participants n=10 Participants	6 Participants n=20 Participants	1 Participants n=45 Participants	3 Participants n=44 Participants	50 Participants n=8 Participants
Region of Enrollment SOUTH KOREA	8 Participants n=10 Participants	22 Participants n=10 Participants	21 Participants n=20 Participants	17 Participants n=45 Participants	10 Participants n=44 Participants	78 Participants n=8 Participants
Region of Enrollment SPAIN	12 Participants n=10 Participants	9 Participants n=10 Participants	9 Participants n=20 Participants	12 Participants n=45 Participants	3 Participants n=44 Participants	45 Participants n=8 Participants
Region of Enrollment SWEDEN	4 Participants n=10 Participants	2 Participants n=10 Participants	1 Participants n=20 Participants	1 Participants n=45 Participants	1 Participants n=44 Participants	9 Participants n=8 Participants
Region of Enrollment TAIWAN	8 Participants n=10 Participants	4 Participants n=10 Participants	7 Participants n=20 Participants	12 Participants n=45 Participants	3 Participants n=44 Participants	34 Participants n=8 Participants
Region of Enrollment TURKEY	18 Participants n=10 Participants	16 Participants n=10 Participants	6 Participants n=20 Participants	6 Participants n=45 Participants	5 Participants n=44 Participants	51 Participants n=8 Participants
Region of Enrollment UKRAINE	18 Participants n=10 Participants	20 Participants n=10 Participants	12 Participants n=20 Participants	11 Participants n=45 Participants	9 Participants n=44 Participants	70 Participants n=8 Participants
Region of Enrollment UNITED KINGDOM	2 Participants n=10 Participants	1 Participants n=10 Participants	0 Participants n=20 Participants	3 Participants n=45 Participants	3 Participants n=44 Participants	9 Participants n=8 Participants
Region of Enrollment UNITED STATES	12 Participants n=10 Participants	11 Participants n=10 Participants	2 Participants n=20 Participants	3 Participants n=45 Participants	8 Participants n=44 Participants	36 Participants n=8 Participants

PRIMARY outcome

Timeframe: Up to 32 months

Population: The randomized analysis set for cohort 1 included all randomized participants in Cohort 1. Data for this outcome measure was planned to be collected and analyzed for Cohort 1 only.

Outcome measures

Outcome measures
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=212 Participants Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=211 Participants Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.
Cohort 1: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)	16.46 Months Interval 13.83 to 19.38	13.70 Months Interval 10.91 to 16.39

PRIMARY outcome

Timeframe: Up to 32 months

Population: The randomized analysis set for cohort 1 BRCA subgroup included all randomized participants in Cohort 1 BRCA subgroup. Data for this outcome measure was planned to be collected and analyzed for BRCA subgroup of Cohort 1 only.

As per BICR, rPFS is time interval from the date of randomization to radiographic progression or death, whichever occurred first. Radiographic progression was determined by: (1) progression of soft tissue lesions measured by CT or MRI as per RECIST 1.1; (2) Progression of bone lesions observed by bone scan based on PCWG3 criteria. PCWG3 criteria: bone progression was confirmed by subsequent scan \>=6 weeks later. Week 8 scan was baseline to which all subsequent scans were compared to determine progression. Confirmatory scan \>=2 new lesions indicate progression; scan does not show \>=2 new lesions means no progression. If Week 8 scan \<2 new bone lesions compared to baseline, the initial scan \>=2 new lesions compared to Week 8 scan indicates progression if confirmed by subsequent scan \>=6 weeks later.

Outcome measures

Outcome measures
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=113 Participants Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=112 Participants Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.
Cohort 1 Breast Cancer Gene (BRCA) Subgroup: Radiographic Progression-Free Survival (rPFS) as Assessed by Blinded Independent Central Review (BICR)	16.56 Months Interval 13.86 to Here, NA signifies that upper limit of 95% confidence interval could not be calculated due to the too low number of participants with a rPFS event observed by the time of analysis.	10.87 Months Interval 8.31 to 13.8

Adverse Events

Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg

Serious events: 76 serious events

Other events: 198 other events

Deaths: 55 deaths

Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg

Serious events: 52 serious events

Other events: 178 other events

Deaths: 59 deaths

Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg

Serious events: 66 serious events

Other events: 117 other events

Deaths: 53 deaths

Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg

Serious events: 45 serious events

Other events: 108 other events

Deaths: 44 deaths

Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg

Serious events: 21 serious events

Other events: 83 other events

Deaths: 9 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=212 participants at risk Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=211 participants at risk Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=123 participants at risk Participants with mCRPC and negative HRR gene alteration, received niraparib 200 mg capsule in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=123 participants at risk Participants with mCRPC and negative HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg n=95 participants at risk Participants with mCRPC and positive HRR gene alteration, received fixed-dose combination (FDC) of niraparib 200 mg and abiraterone acetate 1000 mg combination tablet orally QD with prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 9 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive same treatment in long-term extension phase.
Blood and lymphatic system disorders Anaemia	5.7% 12/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.3% 20/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Leukopenia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Lymphoid Tissue Hyperplasia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Lymphopenia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Neutropenia	1.4% 3/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Asthenia	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Thrombocytopenia	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Acute Coronary Syndrome	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Acute Myocardial Infarction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Angina Pectoris	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Angina Unstable	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Arrhythmia	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Arrhythmia Supraventricular	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Atrial Fibrillation	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Cardiac Arrest	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Cardiac Failure	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Cardiac Failure Acute	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Cardio-Respiratory Arrest	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Cor Pulmonale	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Coronary Artery Disease	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Left Ventricular Dysfunction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Myocardial Infarction	1.4% 3/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.4% 3/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Myocardial Ischaemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Palpitations	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Cardiac disorders Tachycardia	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Endocrine disorders Adrenal Insufficiency	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Eye disorders Blindness Unilateral	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Eye disorders Eye Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Abdominal Mass	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Abdominal Pain	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Abdominal Pain Upper	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Anal Haemorrhage	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Colitis Ischaemic	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Constipation	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Diarrhoea	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Dysphagia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Gastric Ulcer	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Gastritis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Gastrointestinal Haemorrhage	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Haematochezia	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Ileus	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Inguinal Hernia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Intestinal Obstruction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Large Intestinal Obstruction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Nausea	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Rectal Haemorrhage	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Small Intestinal Obstruction	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Vomiting	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Adverse Drug Reaction	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Chest Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Fatigue	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Gait Disturbance	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders General Physical Health Deterioration	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Multiple Organ Dysfunction Syndrome	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Non-Cardiac Chest Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Oedema Peripheral	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Pain	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Peripheral Swelling	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Pyrexia	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Hepatobiliary disorders Cholecystitis Chronic	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Hepatobiliary disorders Hepatic Failure	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Hepatobiliary disorders Hepatitis Acute	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Hepatobiliary disorders Jaundice	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Abscess Oral	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Bacteraemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Bronchitis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Cellulitis	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Clostridium Difficile Infection	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Covid-19	2.8% 6/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Covid-19 Pneumonia	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Diverticulitis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Erysipelas	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Escherichia Bacteraemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Gastroenteritis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Infection	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Lower Respiratory Tract Infection	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Medical Device Site Joint Infection	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Meningitis Aseptic	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Pneumonia	3.3% 7/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.9% 4/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.3% 4/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Post Procedural Sepsis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Pyelonephritis	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Pyelonephritis Acute	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Sepsis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Septic Shock	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Suspected Covid-19	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Tooth Infection	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Urinary Tract Infection	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Urosepsis	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Ankle Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Cardiac Valve Rupture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Fall	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Femoral Neck Fracture	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Femur Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Humerus Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Lower Limb Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Lumbar Vertebral Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Patella Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Post Procedural Pulmonary Embolism	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Radiation Proctitis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Road Traffic Accident	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Spinal Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Subdural Haematoma	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Ulna Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Upper Limb Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Vaccination Complication	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Wound Dehiscence	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Aspartate Aminotransferase Increased	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Dehydration	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Diabetes Mellitus Inadequate Control	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hyperglycaemia	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hypocalcaemia	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hypokalaemia	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hypophagia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Type 2 Diabetes Mellitus	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Back Pain	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Bone Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Fistula	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Osteoarthritis	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Osteonecrosis of Jaw	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Osteoporotic Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Pathological Fracture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Acute Myeloid Leukaemia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of Colon	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Basal Cell Carcinoma	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Cancer	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder Transitional Cell Carcinoma	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Adenocarcinoma Stage I	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung Neoplasm Malignant	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous Cell Carcinoma of Lung	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Carotid Artery Stenosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Cauda Equina Syndrome	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Cerebral Arteriosclerosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Cerebrovascular Accident	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Depressed Level of Consciousness	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Dizziness	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Dysarthria	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Facial Paralysis	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Haemorrhage Intracranial	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Headache	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Hemiparesis	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Ischaemic Cerebral Infarction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Lumbar Radiculopathy	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Malignant Spinal Cord Compression	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Myelopathy	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Peroneal Nerve Palsy	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Spinal Cord Compression	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Transient Ischaemic Attack	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Vascular Encephalopathy	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Psychiatric disorders Completed Suicide	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Acute Kidney Injury	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Bladder Mass	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Bladder Obstruction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Bladder Perforation	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Calculus Bladder	0.94% 2/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Chronic Kidney Disease	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Dysuria	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Haematuria	1.4% 3/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Hydronephrosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Micturition Disorder	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Renal Failure	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Renal Impairment	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Ureteric Obstruction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Urethral Stenosis	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Urinary Retention	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.95% 2/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Urinary Tract Obstruction	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Reproductive system and breast disorders Benign Prostatic Hyperplasia	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Acute Respiratory Failure	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Atelectasis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.4% 3/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Dyspnoea Exertional	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pleural Effusion	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pulmonary Embolism	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.2% 3/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Pulmonary Oedema	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Skin and subcutaneous tissue disorders Actinic Keratosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Aortic Aneurysm	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Arteriosclerosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Circulatory Collapse	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Deep Vein Thrombosis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Embolism	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Hypertension	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Hypertensive Crisis	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Hypovolaemic Shock	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Iliac Artery Rupture	0.00% 0/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Orthostatic Hypotension	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Venous Thrombosis Limb	0.47% 1/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.

Other adverse events

Other adverse events
Measure	Cohort 1: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=212 participants at risk Participants with metastatic castration-resistant prostate cancer (mCRPC) and positive homologous recombination repair (HRR) gene alteration, received niraparib 200 milligrams (mg) capsule in combination with abiraterone acetate 1000 mg tablet orally once daily (QD) and prednisone 5 mg tablet orally twice daily (BID) (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 1: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=211 participants at risk Participants with mCRPC and positive HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 2: Niraparib 200 mg + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=123 participants at risk Participants with mCRPC and negative HRR gene alteration, received niraparib 200 mg capsule in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open label extension phase.	Cohort 2: Placebo + Abiraterone Acetate 1000 mg + Prednisone 10 mg n=123 participants at risk Participants with mCRPC and negative HRR gene alteration, received placebo in combination with abiraterone acetate 1000 mg tablet orally QD and prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 29 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants who received placebo and abiraterone acetate plus prednisone were allowed to cross over to receive niraparib 200 mg and abiraterone acetate 1000 mg plus prednisone 10 mg in the open-label extension phase.	Cohort 3: Niraparib 200 mg and Abiraterone Acetate 1000 mg FDC + Prednisone 10 mg n=95 participants at risk Participants with mCRPC and positive HRR gene alteration, received fixed-dose combination (FDC) of niraparib 200 mg and abiraterone acetate 1000 mg combination tablet orally QD with prednisone 5 mg tablet orally BID (total dose 10 mg) in each 28 days treatment cycle starting from Cycle 1 Day 1 up to 9 months. Participants were then followed up for safety up to 5 years after last dose or until death, loss to follow-up, withdrawal of consent, or study termination. Participants were continued to receive same treatment in long-term extension phase.
Blood and lymphatic system disorders Leukopenia	10.4% 22/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 5/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.2% 3/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Anaemia	44.8% 95/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	20.4% 43/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	48.0% 59/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	15.4% 19/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	38.9% 37/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Lymphopenia	9.0% 19/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.9% 4/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.3% 4/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Neutropenia	13.2% 28/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 12/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	17.1% 21/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Blood and lymphatic system disorders Thrombocytopenia	21.2% 45/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.5% 18/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	19.5% 24/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	11.6% 11/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Abdominal Distension	3.8% 8/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.47% 1/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.1% 5/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Abdominal Pain	4.2% 9/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 12/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.3% 4/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Constipation	30.7% 65/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.7% 29/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	30.9% 38/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	20.3% 25/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	24.2% 23/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Diarrhoea	4.7% 10/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.8% 8/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.1% 10/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Dry Mouth	2.8% 6/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.4% 3/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.1% 5/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.81% 1/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Dyspepsia	6.1% 13/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.8% 6/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.3% 6/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Gastritis	1.4% 3/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.4% 3/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.3% 4/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Nausea	23.6% 50/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.7% 29/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	23.6% 29/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.3% 20/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	26.3% 25/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Gastrointestinal disorders Vomiting	13.2% 28/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.6% 14/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.8% 17/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.9% 11/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.4% 8/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Asthenia	15.6% 33/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.0% 19/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	17.9% 22/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	11.4% 14/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	12.6% 12/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Fatigue	26.4% 56/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.6% 35/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	23.6% 29/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	17.1% 21/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.8% 16/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Oedema Peripheral	9.4% 20/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.5% 18/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.0% 16/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	12.2% 15/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
General disorders Pyrexia	5.7% 12/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.2% 11/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Upper Respiratory Tract Infection	3.3% 7/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.8% 8/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Infections and infestations Urinary Tract Infection	9.0% 19/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.2% 11/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.1% 5/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.2% 3/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Injury, poisoning and procedural complications Fall	5.2% 11/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	11.8% 25/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.0% 16/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.2% 4/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Alanine Aminotransferase Increased	4.7% 10/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.4% 22/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.9% 11/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Aspartate Aminotransferase Increased	5.2% 11/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.5% 20/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.8% 12/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.2% 4/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Blood Alkaline Phosphatase Increased	9.9% 21/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.6% 14/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Blood Creatinine Increased	9.0% 19/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.8% 8/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.1% 5/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Investigations Weight Decreased	9.0% 19/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 5/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.3% 20/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Decreased Appetite	14.2% 30/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.2% 13/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	23.6% 29/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.9% 11/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	13.7% 13/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hyperglycaemia	9.9% 21/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.5% 18/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	14.6% 18/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.1% 10/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hyperkalaemia	8.5% 18/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 12/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hypokalaemia	12.7% 27/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.0% 19/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	12.2% 15/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.5% 10/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Metabolism and nutrition disorders Hyponatraemia	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 5/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.6% 2/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Arthralgia	13.2% 28/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.5% 20/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.9% 11/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	16.3% 20/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Back Pain	14.6% 31/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	20.9% 44/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	15.4% 19/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	20.3% 25/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Bone Pain	9.9% 21/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	11.4% 24/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	8.1% 10/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.3% 5/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Muscular Weakness	3.3% 7/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.9% 4/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	1.9% 4/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.2% 11/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.3% 4/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	1.1% 1/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Musculoskeletal and connective tissue disorders Pain in Extremity	4.7% 10/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.6% 14/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.6% 13/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.2% 4/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Dizziness	11.3% 24/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 12/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.6% 13/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.6% 13/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Nervous system disorders Headache	7.5% 16/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	9.0% 19/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.4% 3/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.4% 7/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Psychiatric disorders Insomnia	10.4% 22/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.8% 8/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.2% 3/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Renal and urinary disorders Haematuria	5.7% 12/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	3.8% 8/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 7/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.3% 9/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	0.00% 0/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Cough	7.1% 15/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.7% 10/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	2.1% 2/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Respiratory, thoracic and mediastinal disorders Dyspnoea	15.6% 33/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	5.7% 12/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	12.2% 15/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.5% 8/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	6.3% 6/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Hot Flush	7.1% 15/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	7.1% 15/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.9% 6/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	10.6% 13/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	4.2% 4/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.
Vascular disorders Hypertension	31.1% 66/212 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	20.9% 44/211 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	33.3% 41/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	22.0% 27/123 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.	15.8% 15/95 • Up to 32 months The safety analysis set for Cohort 1 and Cohort 2 included all randomized participants who received at least 1 dose of study drug in Cohort 1 or Cohort 2. The safety analysis set for Cohort 3 included all participants who received at least 1 dose of study drug in Cohort 3.

Additional Information

Executive Medical Director Oncology

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER