Trial Outcomes & Findings for Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 (Alobresib) as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer (NCT NCT02607228)

Last Updated: 2020-12-08

Results Overview

A DLT was a toxicity, considered possibly related to alobresib, and which occurred during the DLT assessment window (Days 1 through 28) in each cohort: Grade ≥ 4 neutropenia (absolute neutrophil count (ANC) \< 500/mm\^3), Grade ≥ 3 neutropenia (ANC\< 1000/mm\^3) with fever (a single temperature \> 38.3°C or a sustained temperature of ≥ 38°C for more than 1 hour (h)), Grade ≥ 3 thrombocytopenia, Grade ≥ 2 bleeding (eg, gastrointestinal, respiratory, epistaxis, purpura), Grade ≥ 3 non hematologic toxicity, except- Grade 3 nausea or emesis with maximum duration of 48 h on adequate medical therapy and Grade 3 diarrhea which persists for \< 72 h in the absence of maximal medical therapy, Grade ≥ 2 non hematologic treatment emergent adverse event (TEAE) that in the opinion of the investigator was of potential clinical significance such that further dose escalation would expose participants to unacceptable risk, treatment interruption ≥ 7 days due to unresolved toxicity.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

31 participants

Primary outcome timeframe

Day 1 through Day 28

Results posted on

2020-12-08

Participant Flow

Participants were enrolled at 4 study sites in the United States. The first participant was screened on 08 December 2015. The last study visit occurred on 03 September 2019. Phase 2 Dose Expansion of the study was not conducted. Results are reported for only Dose Escalation Monotherapy and Combination Therapy.

43 participants were screened.

Participant milestones

Participant milestones
Measure	Monotherapy: Alobresib 2 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Overall Study STARTED	5	4	3	6	5	6	2
Overall Study COMPLETED	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	5	4	3	6	5	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Monotherapy: Alobresib 2 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Overall Study Progressive Disease	4	3	1	5	4	3	1
Overall Study Adverse Event	1	0	1	0	1	1	1
Overall Study Investigator's Discretion	0	0	1	0	0	1	0
Overall Study Withdrew Consent	0	1	0	0	0	1	0
Overall Study Study Terminated by Sponsor	0	0	0	1	0	0	0

Baseline Characteristics

Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GS-5829 (Alobresib) as a Single Agent and In Combination With Enzalutamide in Participants With Metastatic Castrate-Resistant Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Total n=31 Participants Total of all reporting groups
Age, Continuous	68.2 years STANDARD_DEVIATION 9.28 • n=5 Participants	67.3 years STANDARD_DEVIATION 10.69 • n=7 Participants	67.7 years STANDARD_DEVIATION 5.69 • n=5 Participants	66.8 years STANDARD_DEVIATION 9.39 • n=4 Participants	69.2 years STANDARD_DEVIATION 6.61 • n=21 Participants	62.5 years STANDARD_DEVIATION 10.23 • n=8 Participants	67.0 years STANDARD_DEVIATION 0.00 • n=8 Participants	66.7 years STANDARD_DEVIATION 8.25 • n=24 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=8 Participants	2 Participants n=8 Participants	31 Participants n=24 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	2 Participants n=24 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	3 Participants n=21 Participants	5 Participants n=8 Participants	2 Participants n=8 Participants	28 Participants n=24 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Race/Ethnicity, Customized Race · Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=8 Participants	0 Participants n=8 Participants	3 Participants n=24 Participants
Race/Ethnicity, Customized Race · White	4 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=21 Participants	5 Participants n=8 Participants	2 Participants n=8 Participants	27 Participants n=24 Participants
Race/Ethnicity, Customized Race · Other	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	1 Participants n=24 Participants
Region of Enrollment United States	5 Participants n=5 Participants	4 Participants n=7 Participants	3 Participants n=5 Participants	6 Participants n=4 Participants	5 Participants n=21 Participants	6 Participants n=8 Participants	2 Participants n=8 Participants	31 Participants n=24 Participants

PRIMARY outcome

Timeframe: Day 1 through Day 28

Population: The DLT Analysis Set included all participants in the Safety Analysis Set who completed all treatment and safety procedures through Day 28, inclusive, or experienced a DLT prior to Day 28, exclusive.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: Number of Participants Experienced Dose Limiting Toxicities (DLTs)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

PRIMARY outcome

Timeframe: Week 24

Population: The Phase 2 Dose Expansion of the study was not conducted.

The non-progression rate at Week 24 was defined as the proportion of participants who did not progress by Week 24.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Monotherapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Day 8 and Cycle 2 Day 1; Combination therapy: Predose, 0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose on Cycle 1 Days 1 and 15

Population: The PK Analysis Set included participants who took at least 1 dose of study drug and have at least 1 non-missing postdose concentration value. Participants with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Cmax is the maximum observed concentration of drug in plasma.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib Cycle 1 Day 1	—	—	—	—	—	111.07 ng/mL Standard Deviation 37.957	199.00 ng/mL Standard Deviation 9.899
Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib Cycle 1 Day 8	263.00 ng/mL Standard Deviation 141.875	263.75 ng/mL Standard Deviation 132.011	367.33 ng/mL Standard Deviation 49.359	293.33 ng/mL Standard Deviation 123.362	526.00 ng/mL Standard Deviation 280.391	—	—
Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib Cycle 1 Day 15	—	—	—	—	—	84.4 ng/mL Standard Deviation 48.58	173.5 ng/mL Standard Deviation 28.99
Phase 1b Dose Escalation: Cmax: Maximum Observed Plasma Concentration of Alobresib Cycle 2 Day 1	—	220.50 ng/mL Standard Deviation 95.459	—	203.50 ng/mL Standard Deviation 143.543	641.00 ng/mL Standard Deviation NA Standard Deviation (SD) was not estimable for 1 participant.	—	—

SECONDARY outcome

Population: Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

Ctau is the observed concentration of drug in plasma at the end of dosing.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib Cycle 1 Day 8	180.00 ng/mL Standard Deviation 77.679	156.78 ng/mL Standard Deviation 100.307	141.67 ng/mL Standard Deviation 22.811	70.93 ng/mL Standard Deviation 32.905	157.20 ng/mL Standard Deviation 126.996	—	—
Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib Cycle 1 Day 15	—	—	—	—	—	8.8 ng/mL Standard Deviation 7.77	3.9 ng/mL Standard Deviation 3.21
Phase 1b Dose Escalation: Ctau: Observed Drug Concentration at the End of the Dosing Interval of Alobresib Cycle 2 Day 1	—	127.60 ng/mL Standard Deviation 59.963	—	33.80 ng/mL Standard Deviation NA SD was not estimable for 1 participant.	268.00 ng/mL Standard Deviation NA SD was not estimable for 1 participant.	—	—

SECONDARY outcome

Population: Participants in the PK Analysis Set with available data were analyzed. Monotherapy: Samples were not collected at Cycle 1 Day 1 and Cycle 1 Day 15; samples were only collected for participants who received alobresib 3 mg, 6 mg and 9 mg doses at Cycle 2 Day 1. Combination Therapy: Samples were not collected at Cycle 1 Day 8 and Cycle 2 Day 1.

AUClast is the concentration of drug over time zero to last concentration (area under the plasma concentration versus time curve).

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib Cycle 1 Day 1	—	—	—	—	—	1026.99 h*ng/mL Standard Deviation 359.220	1741.42 h*ng/mL Standard Deviation 737.521
Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib Cycle 1 Day 8	4207.55 h*ng/mL Standard Deviation 2319.854	3742.30 h*ng/mL Standard Deviation 2106.308	4646.08 h*ng/mL Standard Deviation 890.441	3105.70 h*ng/mL Standard Deviation 1008.730	4494.79 h*ng/mL Standard Deviation 4124.948	—	—
Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib Cycle 1 Day 15	—	—	—	—	—	652.7 h*ng/mL Standard Deviation 395.52	701.3 h*ng/mL Standard Deviation 353.25
Phase 1b Dose Escalation: AUClast: Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration of Alobresib Cycle 2 Day 1	—	3264.79 h*ng/mL Standard Deviation 2024.141	—	1709.71 h*ng/mL Standard Deviation 264.402	10264.74 h*ng/mL Standard Deviation NA SD was not estimable for 1 participant.	—	—

SECONDARY outcome

AUCtau is defined as the concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib Cycle 1 Day 8	4264.51 h*ng/mL Standard Deviation 2384.628	3758.92 h*ng/mL Standard Deviation 2076.013	4655.48 h*ng/mL Standard Deviation 949.099	3128.58 h*ng/mL Standard Deviation 998.059	7217.02 h*ng/mL Standard Deviation 4559.957	—	—
Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib Cycle 1 Day 15	—	—	—	—	—	765.3 h*ng/mL Standard Deviation 373.39	701.3 h*ng/mL Standard Deviation 353.25
Phase 1b Dose Escalation: AUCtau: Area Under the Plasma Concentration Versus Time Curve Over the Dosing Interval of Alobresib Cycle 2 Day 1	—	3243.01 h*ng/mL Standard Deviation 2110.324	—	1522.75 h*ng/mL Standard Deviation NA SD was not estimable for 1 participant.	10264.74 h*ng/mL Standard Deviation NA SD was not estimable for 1 participant.	—	—

SECONDARY outcome

Tmax is the time observed for the Cmax of alobresib.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib Cycle 1 Day 1	—	—	—	—	—	1.07 hours Interval 0.5 to 2.92	0.46 hours Interval 0.42 to 0.5
Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib Cycle 1 Day 8	0.50 hours Interval 0.48 to 23.85	0.66 hours Interval 0.5 to 1.05	0.58 hours Interval 0.5 to 2.0	1.42 hours Interval 0.5 to 3.97	0.72 hours Interval 0.5 to 2.08	—	—
Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib Cycle 1 Day 15	—	—	—	—	—	0.5 hours Interval 0.5 to 7.9	0.5 hours Interval 0.5 to 0.5
Phase 1b Dose Escalation: Tmax: Time (Observed Time Point) of Cmax of Alobresib Cycle 2 Day 1	—	1.76 hours Interval 0.5 to 3.02	—	4.93 hours Interval 3.87 to 6.0	4.08 hours Interval 4.08 to 4.08	—	—

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: Participants in the Full Analysis Set were analyzed.

PSA response was defined as percentage of participants with ≥ 30% decline in PSA from baseline by 12 weeks.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Percentage of Participants Who Had ≥ 30% Reduction in Prostate Specific Antigen (PSA) From Baseline at Week 12	0.0 percentage of participants	0.0 percentage of participants	33.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Participants in the Full Analysis Set were analyzed.

PFS was defined as the interval from first dose date of study drug to the earlier of the first documentation of definitive disease progression (assessed per PCWG2) or death from any cause. PCWG2 criteria for progression was determined as 'Decline from baseline' when record start of therapy to first prostate-specific antigen (PSA) increase that is ≥ 25% and ≥ 2 ng/mL above the nadir and confirmed by a second value 3 or more weeks later; 'No decline from baseline' when PSA progression ≥ 25% and ≥ 2 ng/mL after 12 weeks.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=2 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=5 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=1 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Progression Free Survival (PFS)	2.61 months Interval 1.58 to 8.61	2.10 months Interval 1.97 to 2.6	4.17 months Interval 2.79 to 5.55	2.78 months Interval 2.69 to 11.07	2.69 months Interval 0.53 to 14.0	3.25 months Interval 1.15 to 21.59	5.98 months Upper and lower limit of 95% confidence interval are not estimable for 1 participant.

SECONDARY outcome

Timeframe: Up to approximately 4 years

Population: Participants in the Full Analysis Set were analyzed.

OS is defined as the interval from first dose date of study drug to death from any cause.

Outcome measures

Outcome measures
Measure	Monotherapy: Alobresib 2 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 Participants Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 Participants Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 Participants Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Overall Survival (OS)	NA months Data were not evaluable because participants discontinued the study without death.	NA months Interval 3.12 to Data were not evaluable because participants discontinued the study without death.	NA months Data were not evaluable because participants discontinued the study without death.	NA months Data were not evaluable because participants discontinued the study without death.	NA months Data were not evaluable because participants discontinued the study without death.	NA months Interval 1.15 to Data were not evaluable because participants discontinued the study without death.	NA months Data were not evaluable because participants discontinued the study without death.

Adverse Events

Monotherapy: Alobresib 2 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Monotherapy: Alobresib 3 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 1 deaths

Monotherapy: Alobresib 4 mg

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Monotherapy: Alobresib 6 mg

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Monotherapy: Alobresib 9 mg

Serious events: 2 serious events

Other events: 5 other events

Deaths: 0 deaths

Combination Therapy: Alobresib 3 mg + Enzalutamide

Serious events: 2 serious events

Other events: 5 other events

Deaths: 1 deaths

Combination Therapy: Alobresib 6 mg + Enzalutamide

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Monotherapy: Alobresib 2 mg n=5 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 participants at risk Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 participants at risk Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Eye disorders Retinal detachment	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Diverticular perforation	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Asthenia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Fatigue	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Pyrexia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Urinary tract infection	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Fall	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Back pain	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Central nervous system lesion	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Cerebrovascular accident	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Embolic stroke	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Acute kidney injury	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Reproductive system and breast disorders Pelvic pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.

Other adverse events

Other adverse events
Measure	Monotherapy: Alobresib 2 mg n=5 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 2 mg tablets administered orally once daily to determine the maximum tolerated dose (MTD).	Monotherapy: Alobresib 3 mg n=4 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 3 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 4 mg n=3 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 4 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 6 mg n=6 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 6 mg tablets administered orally once daily to determine the MTD.	Monotherapy: Alobresib 9 mg n=5 participants at risk Participants who had progressed on either abiraterone and/or enzalutamide, received alobresib 9 mg tablets administered orally once daily to determine the MTD.	Combination Therapy: Alobresib 3 mg + Enzalutamide n=6 participants at risk Participants who had progressed on abiraterone, received alobresib 3 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.	Combination Therapy: Alobresib 6 mg + Enzalutamide n=2 participants at risk Participants who had progressed on abiraterone, received alobresib 6 mg tablets administered orally once daily in combination with enzalutamide 160 mg capsules administered orally once daily.
Blood and lymphatic system disorders Anaemia	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Ear and labyrinth disorders Ear pruritus	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Abdominal distension	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Abdominal pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Constipation	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Diarrhoea	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 3/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Dry mouth	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Dysphagia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Eructation	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Nausea	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	60.0% 3/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Stomatitis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Asthenia	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Catheter site extravasation	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Chest pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Chills	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Device related thrombosis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Early satiety	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Fatigue	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	100.0% 3/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 3/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	80.0% 4/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 2/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Feeling cold	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Gait disturbance	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Influenza like illness	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Non-cardiac chest pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Oedema peripheral	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
General disorders Pain	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Abdominal infection	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Herpes zoster	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Kidney infection	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Oral candidiasis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Tooth infection	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Infections and infestations Viral infection	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Contusion	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Fall	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Iliotibial band syndrome	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Joint injury	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Muscle strain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Skin abrasion	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Upper limb fracture	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Injury, poisoning and procedural complications Wound haemorrhage	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Investigations Aspartate aminotransferase increased	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Investigations Blood bilirubin increased	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Investigations Blood creatinine increased	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Investigations Platelet count decreased	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Investigations Weight decreased	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Metabolism and nutrition disorders Decreased appetite	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	80.0% 4/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Metabolism and nutrition disorders Dehydration	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	40.0% 2/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Metabolism and nutrition disorders Hyperkalaemia	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	66.7% 2/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 2/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Flank pain	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Groin pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Joint swelling	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 3/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Musculoskeletal and connective tissue disorders Pathological fracture	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Burning sensation	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Cognitive disorder	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Dysgeusia	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Headache	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Hemiparesis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Memory impairment	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Neuropathy peripheral	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Paraesthesia	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Psychiatric disorders Abnormal dreams	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Psychiatric disorders Anxiety	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Psychiatric disorders Confusional state	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Psychiatric disorders Depression	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Acute kidney injury	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Dysuria	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Haematuria	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Pollakiuria	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Renal pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	50.0% 1/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Urinary retention	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Urinary tract disorder	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Renal and urinary disorders Urinary tract obstruction	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Reproductive system and breast disorders Erectile dysfunction	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Reproductive system and breast disorders Pelvic pain	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 1/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Epistaxis	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Skin and subcutaneous tissue disorders Erythema	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	33.3% 2/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Vascular disorders Deep vein thrombosis	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	25.0% 1/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Vascular disorders Hot flush	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Vascular disorders Hypertension	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	16.7% 1/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.
Vascular disorders Hypotension	0.00% 0/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/4 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/3 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	20.0% 1/5 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/6 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.	0.00% 0/2 • Adverse Events: From first dose through last dose of the study drug (maximum: 131 weeks) plus 30 days; All-Cause Mortality: First dose date up to approximately 4 years The Safety Analysis Set included all participants who received \>= 1 dose of study treatment with treatment group designated according to actual treatment.

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years.
Publication restrictions are in place

Restriction type: OTHER