Trial Outcomes & Findings for A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer (NCT NCT04194944)

NCT ID: NCT04194944

Last Updated: 2025-10-21

Results Overview

PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE3
• Target enrollment: 261 participants
• Primary outcome timeframe: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months
• Results posted on: 2025-10-21

Participant Flow

If a participant has a recorded death on study, or is alive and being followed but off treatment, then the participant can be considered to be study completer.

Participant milestones

Measure	Selpercatinib (TRT A) 160 milligram (mg) Selpercatinib administered orally, twice daily (BID) continuously in 21-day cycles.	Pemetrexed and Platinum With or Without Pembrolizumab (TRT B) Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose 750 mg\]) IV, or cisplatin 75mg/m2 IV on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Overall Study STARTED	159	102
Overall Study Received at Least One Dose of Study Drug	158	98
Overall Study COMPLETED	61	70
Overall Study NOT COMPLETED	98	32

Reasons for withdrawal

Measure	Selpercatinib (TRT A) 160 milligram (mg) Selpercatinib administered orally, twice daily (BID) continuously in 21-day cycles.	Pemetrexed and Platinum With or Without Pembrolizumab (TRT B) Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose 750 mg\]) IV, or cisplatin 75mg/m2 IV on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Overall Study Lost to Follow-up	3	0
Overall Study Withdrawal by Subject	2	2
Overall Study On Treatment	93	30

Baseline Characteristics

A Study of Selpercatinib (LY3527723) in Participants With Advanced or Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer

Baseline characteristics by cohort

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally BID continuously in 21-day cycles.	Pemetrexed and Platinum With or Without Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin (AUC 5 \[maximum dose 750 mg\] IV) or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.	Total n=261 Participants Total of all reporting groups
Region of Enrollment Brazil	7 Participants n=5 Participants	1 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Japan	15 Participants n=5 Participants	10 Participants n=7 Participants	25 Participants n=5 Participants
Region of Enrollment Argentina	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Poland	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment France	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Ukraine	0 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Spain	7 Participants n=5 Participants	9 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment Canada	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Turkey	8 Participants n=5 Participants	0 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment Belgium	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Taiwan	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Region of Enrollment Italy	20 Participants n=5 Participants	12 Participants n=7 Participants	32 Participants n=5 Participants
Region of Enrollment Mexico	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Israel	1 Participants n=5 Participants	4 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Germany	5 Participants n=5 Participants	4 Participants n=7 Participants	9 Participants n=5 Participants
Age, Continuous	60.2 years STANDARD_DEVIATION 11.3 • n=5 Participants	60.8 years STANDARD_DEVIATION 11.4 • n=7 Participants	60.4 years STANDARD_DEVIATION 11.3 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	57 Participants n=7 Participants	143 Participants n=5 Participants
Sex: Female, Male Male	73 Participants n=5 Participants	45 Participants n=7 Participants	118 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Asian	92 Participants n=5 Participants	52 Participants n=7 Participants	144 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	58 Participants n=5 Participants	43 Participants n=7 Participants	101 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Region of Enrollment Hong Kong	4 Participants n=5 Participants	1 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment Czechia	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment Russia	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment Greece	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment Netherlands	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Region of Enrollment South Korea	8 Participants n=5 Participants	8 Participants n=7 Participants	16 Participants n=5 Participants
Region of Enrollment China	62 Participants n=5 Participants	28 Participants n=7 Participants	90 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

Population: Intent to Treat (ITT) Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment. Participants censored: TRT A: 80, TRT B: 34.

PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) (With Pembrolizumab)	24.84 Months Interval 16.89 to Upper limit of 95% confidence interval is not evaluable due to high censoring.	11.17 Months Interval 8.77 to 16.76

PRIMARY outcome

Timeframe: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received. Participants censored: TRT A: 98, TRT B:45.

PFS is defined as the time from randomization until the occurrence of documented disease progression by the BICR, per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria, or death from any cause in the absence of BICR-documented progressive disease.

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
PFS by BICR (With or Without Pembrolizumab)	24.84 Months Interval 17.31 to Upper limit of 95% confidence interval is not evaluable due to high censoring.	11.17 Months Interval 8.77 to 16.76

SECONDARY outcome

Timeframe: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment.

DCR by BICR (with Pembrolizumab) is defined as the number of participants who achieve a BOR of complete response (CR), partial response (PR), or stable disease (SD) lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Percentage of Participant With Disease Control Rate (DCR) by BICR (With Pembrolizumab)	89.1 Percentage of Participants Interval 82.5 to 93.9	84.3 Percentage of Participants Interval 74.7 to 91.4

SECONDARY outcome

Timeframe: Baseline to Progressive Disease or Death from Any Cause Up to 31 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

DCR by BICR (with or without Pembrolizumab) is defined as the number of participants who achieve a BOR of CR, PR, or SD lasting 16 or more weeks divided by the total number of participants randomized to each treatment arm.

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Percentage of Participant With DCR by BICR (With or Without Pembrolizumab)	89.3 Percentage of Participants Interval 83.4 to 93.7	82.4 Percentage of Participants Interval 73.6 to 89.2

SECONDARY outcome

Timeframe: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment. Participants censored: TRT A: 103; TRT B: 62

PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
PFS2 (With Pembrolizumab)	NA Months Data not available due to high censoring.	NA Months Data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline to Second Disease Progression or Death from Any Cause Up to 38 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received. Participants censored: TRT A: 126; TRT B: 77

PFS2 is defined as the time from randomization to disease progression on the next line of treatment or death from any cause in the absence of observed disease progression.

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
PFS2 (With or Without Pembrolizumab)	NA Months Data not available due to high censoring.	NA Months Data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline through Disease Progression or Death Up to 31 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment.

ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Overall Response Rate (ORR): Percentage of Participants With Complete Response (CR) or Partial Response (PR) by BICR (With Pembrolizumab)	83.7 Percentage of participants Interval 76.2 to 89.6	65.1 Percentage of participants Interval 53.8 to 75.2

SECONDARY outcome

Timeframe: Baseline through Disease Progression or Death Up to 31 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received.

ORR is defined as the number of participants who achieve a best overall response (BOR) of complete response (CR) or partial response (PR) divided by the total number of participants randomized to each treatment arm.

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
ORR: Percentage of Participants With CR or PR by BICR (With or Without Pembrolizumab)	83.6 Percentage of Participants Interval 77.0 to 89.0	62.7 Percentage of Participants Interval 52.6 to 72.1

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment. Participants censored: TRT A:74; TRT B: 25.

DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.

Outcome measures

Measure	Selpercatinib (TRT A) n=108 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=54 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Duration of Response (DoR) by BICR (With Pembrolizumab)	24.18 Months Interval 17.94 to Upper limit of 95% confidence interval not available due to high censoring.	11.47 Months Interval 9.66 to 23.26

SECONDARY outcome

Timeframe: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause Up to 31 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received. Participants censored: TRT A: 90; TRT B: 33.

DoR was defined as the time from the date that measurement criteria for CR or PR (whichever is first recorded) were first met until the first date that disease was recurrent or documented disease progression was observed, or the date of death from any cause in the absence of documented disease progression or recurrence. The DOR according to both BICR and investigator-assessed BOR was evaluated per RECIST 1.1 criteria.

Outcome measures

Measure	Selpercatinib (TRT A) n=133 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=64 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
DOR by BICR (With or Without Pembrolizumab)	24.18 Months Interval 17.94 to Upper limit of 95% Confidence Interval unavailable due to high censoring.	11.99 Months Interval 9.69 to 23.26

SECONDARY outcome

Timeframe: Baseline to Date of Death from Any Cause Up to 38 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment. Participants censored: TRT A: 104; TRT B: 68.

Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data was censored on the last date the participant is known to be alive.

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Overall Survival (OS) (With Pembrolizumab)	NA Months Median OS data not available due to high censoring.	NA Months Median OS data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline to Date of Death from Any Cause Up to 38 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received. Participants censored: TRT A: 127; TRT B: 84.

Overall survival was defined as the time from randomization until death from any cause. If the participant was alive or lost to follow-up at the time of data analysis, OS data will be censored on the last date the participant is known to be alive.

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
OS (With or Without Pembrolizumab)	33.05 Months Interval 33.05 to Upper limit of 95% Confidence Interval unavailable due to high censoring.	NA Months Data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline through Central Nervous System (CNS) Progression or Death up to 31 Months

Population: CNS Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment who had baseline CNS assessment and who had CNS metastasis at baseline.

Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=21 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=21 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST (Response Evaluation Criteria in Solid Tumors) 1.1 by BICR (With Pembrolizumab)	81 Percentage of participants Interval 58.1 to 94.6	57.1 Percentage of participants Interval 34.0 to 78.2

SECONDARY outcome

Timeframe: Baseline through CNS Progression or Death Up to 31 Months

Population: CNS Overall: All participants included in the ITT population who had baseline CNS assessment and who had CNS metastasis at baseline.

Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RECIST 1.1 by BICR (with or without Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=25 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=26 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Intracranial ORR: Percentage of Participants With Intracranial CR or PR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)	84.0 Percentage of participants Interval 63.9 to 95.5	50.0 Percentage of participants Interval 29.9 to 70.1

SECONDARY outcome

Timeframe: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months

Population: CNS Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment who had baseline CNS assessment and who had CNS metastasis at baseline. Participants censored: TRT A: 13; TRT B: 9.

Intracranial DOR per RECIST 1.1 by BICR (with Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=17 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=12 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Median Intracranial DOR Per RECIST 1.1 by BICR (With Pembrolizumab)	NA Months Interval 14.75 to Median and upper limit of 95% Confidence Interval unavailable due to high censoring.	NA Months Interval 8.74 to Median and upper limit of 95% Confidence Interval unavailable due to high censoring.

SECONDARY outcome

Timeframe: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months

Population: CNS Overall: All participants included in the ITT population who had baseline CNS assessment and who had CNS metastasis at baseline. Participants censored: TRT A: 15; TRT B: 9.

Median Intracranial DOR per RECIST 1.1 by BICR (with or without Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=21 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=13 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Median Intracranial DOR Per RECIST 1.1 by BICR (With or Without Pembrolizumab)	NA Months Interval 9.53 to Upper limit of 95% Confidence Interval unavailable due to high censoring.	13.40 Months Interval 4.17 to Upper limit of 95% Confidence Interval unavailable due to high censoring.

SECONDARY outcome

Timeframe: Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months

Population: ITT Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment. Participants censored: TRT A: 99; TRT B: 47.

Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-Symptom Assessment Questionnaire (SAQ) (with Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=129 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=83 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Time to Deterioration of Pulmonary Symptoms (With Pembrolizumab)	NA Months Data not available due to high censoring.	1.9 Months Interval 0.7 to 6.6

SECONDARY outcome

Timeframe: Baseline to Deterioration of Pulmonary Symptoms Up to 31 Months

Population: ITT Population: All randomized participants, even if a participant did not take the assigned treatment, did not receive the correct treatment, or otherwise did not follow the protocol. Participants were analyzed according to the treatment arm they were assigned to regardless of what actual treatment they received. Participants censored: TRT A: 121; TRT B: 58.

Time to Deterioration of Pulmonary Symptoms Measured by the NSCLC-SAQ (with or without Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=159 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=102 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Time to Deterioration of Pulmonary Symptoms (With or Without Pembrolizumab)	NA Months Data not available due to high censoring.	1.6 Months Interval 0.7 to 4.9

SECONDARY outcome

Timeframe: Baseline

The Concordance of the Local Lab and the Central Lab RET Results: Percentage of Participants with RET-Positive Specimens as Called by the Central Lab, which is also RET-Positive as Called by a Local Lab (Positive Percent Agreement)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through CNS Progression or Death Up to 31 Months

Population: CNS Pembrolizumab: Participants included in the ITT population who were stratified with the intent to receive pembrolizumab in the event of the control-arm assignment who had baseline CNS assessment and who had CNS metastasis at baseline. Number of participants censored: TRT A = 112; TRT B = 59.

Time to CNS Progression per RECIST 1.1 by BICR (with Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=120 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=72 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Median Time to CNS Progression Per RECIST 1.1 by BICR (With Pembrolizumab)	NA Months Data not available due to high censoring.	NA Months Data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline through CNS Progression or Death Up to 31 Months

Population: CNS Overall: All participants included in the ITT population who had baseline CNS assessment and who had CNS metastasis at baseline. Participants censored: TRT A: 137; TRT B: = 73.

Time to CNS Progression per RECIST 1.1 by BICR (with or without Pembrolizumab)

Outcome measures

Measure	Selpercatinib (TRT A) n=146 Participants 160 mg Selpercatinib administered orally, BID continuously in 21-day cycles.	Pemetrexed and Platinum With Pembrolizumab (TRT B) n=88 Participants Pemetrexed 500 mg/m2, IV on Day 1 Q3W plus investigator's choice of carboplatin AUC 5 (maximum dose 750 mg) IV or cisplatin 75mg/m2, IV on Day 1 Q3W for 4 cycles, plus investigator's choice with 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Median Time to CNS Progression Per RECIST 1.1 by BICR (With or Without Pembrolizumab)	NA Months Data not available due to high censoring.	NA Months Data not available due to high censoring.

SECONDARY outcome

Timeframe: Baseline through CNS Progression or Death Up to 31 Months

Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with Pembrolizumab)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline through CNS Progression or Death Up to 31 Months

Intracranial ORR: Percentage of Participants with Intracranial CR or PR per RANO-BM by BICR (with or without Pembrolizumab)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months

Intracranial DOR per RANO-BM by BICR (with Pembrolizumab)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Date of Intracranial CR or PR to Date of CNS Progression or Death Due to Any Cause Up to 31 Months

Intracranial DOR per RANO-BM by BICR (with or without Pembrolizumab)

Outcome measures

Outcome data not reported

Adverse Events

Selpercatinib (TRT A)

Serious events: 55 serious events

Other events: 156 other events

Deaths: 32 deaths

Carboplatin or Cisplatin+Pemetrexed+/-Pembrolizumab (TRT B)

Serious events: 23 serious events

Other events: 97 other events

Deaths: 17 deaths

Serious adverse events

Measure	Selpercatinib (TRT A) n=158 participants at risk 160 milligram (mg) Selpercatinib administered orally, twice daily (BID continuously in 21-day cycles.	Carboplatin or Cisplatin+Pemetrexed+/-Pembrolizumab (TRT B) n=98 participants at risk Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus at the investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose 750 mg\]) IV, or cisplatin 75mg/m2 IV on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Blood and lymphatic system disorders Anaemia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Blood and lymphatic system disorders Neutropenia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Angina pectoris	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Atrial fibrillation	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Cardiac arrest	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Cardiac failure	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Myocardial infarction	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Myocardial ischaemia	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Cardiac disorders Pericardial effusion	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Abdominal pain	0.63% 1/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Ascites	1.9% 3/158 • Number of events 7 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Enterocolitis	0.63% 1/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Gastritis erosive	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Haematemesis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Ileus	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Inguinal hernia	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Intestinal obstruction	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Pancreatitis	0.63% 1/158 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Pancreatitis acute	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Small intestinal haemorrhage	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Volvulus	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Asthenia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Chest pain	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Malaise	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Oedema peripheral	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Pyrexia	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Sudden death	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Hepatobiliary disorders Cholecystitis	1.9% 3/158 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Hepatobiliary disorders Hepatic function abnormal	2.5% 4/158 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Hepatobiliary disorders Immune-mediated hepatic disorder	1.3% 2/158 • Number of events 5 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Immune system disorders Anaphylactic shock	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Immune system disorders Hypersensitivity	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Covid-19	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Covid-19 pneumonia	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Erysipelas	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Herpes zoster	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Infectious pleural effusion	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Meningitis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Peritonitis	0.63% 1/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Pneumonia	1.9% 3/158 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Pneumonia viral	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Sepsis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Soft tissue infection	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Urinary tract infection	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Urosepsis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Injury, poisoning and procedural complications Femur fracture	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Injury, poisoning and procedural complications Procedural haemorrhage	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Alanine aminotransferase increased	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Aspartate aminotransferase increased	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Blood creatinine increased	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Electrocardiogram t wave abnormal	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Hepatic enzyme increased	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Neutrophil count decreased	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Platelet count decreased	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 12 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Decreased appetite	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hyperglycaemia	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypokalaemia	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hyponatraemia	0.63% 1/158 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Malnutrition	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Musculoskeletal and connective tissue disorders Back pain	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant pleural effusion	1.3% 2/158 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Cerebral infarction	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Dizziness	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Spinal cord compression	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	2.0% 2/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Renal and urinary disorders Acute kidney injury	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Chylothorax	0.63% 1/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.3% 2/158 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.4% 7/158 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Dermatitis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Drug eruption	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Vascular disorders Hypertension	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Vascular disorders Jugular vein thrombosis	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Vascular disorders Venous thrombosis limb	0.63% 1/158 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").

Other adverse events

Measure	Selpercatinib (TRT A) n=158 participants at risk 160 milligram (mg) Selpercatinib administered orally, twice daily (BID continuously in 21-day cycles.	Carboplatin or Cisplatin+Pemetrexed+/-Pembrolizumab (TRT B) n=98 participants at risk Pemetrexed 500 milligrams per meter squared (mg/m2) administered intravenously (IV) on Day 1, every 3 weeks (Q3W), plus at the investigator's choice of carboplatin area under the concentration versus time curve 5 (AUC 5 \[maximum dose 750 mg\]) IV, or cisplatin 75mg/m2 IV on Day 1 Q3W for 4 cycles, plus investigator's choice with or without 200 mg pembrolizumab IV on Day 1 Q3W up to 35 cycles.
Blood and lymphatic system disorders Anaemia	11.4% 18/158 • Number of events 35 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	58.2% 57/98 • Number of events 209 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Blood and lymphatic system disorders Leukopenia	7.0% 11/158 • Number of events 22 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	8.2% 8/98 • Number of events 37 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Blood and lymphatic system disorders Neutropenia	3.8% 6/158 • Number of events 13 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	18.4% 18/98 • Number of events 61 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Blood and lymphatic system disorders Thrombocytopenia	7.0% 11/158 • Number of events 17 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	10.2% 10/98 • Number of events 20 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Endocrine disorders Hyperthyroidism	2.5% 4/158 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	7.1% 7/98 • Number of events 7 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Endocrine disorders Hypothyroidism	3.2% 5/158 • Number of events 7 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Eye disorders Lacrimation increased	1.9% 3/158 • Number of events 5 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	13.3% 13/98 • Number of events 16 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Abdominal discomfort	5.7% 9/158 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	3.1% 3/98 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Abdominal distension	5.1% 8/158 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	3.1% 3/98 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Abdominal pain	11.4% 18/158 • Number of events 34 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	7.1% 7/98 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Abdominal pain upper	12.7% 20/158 • Number of events 31 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	13.3% 13/98 • Number of events 30 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Ascites	5.7% 9/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Constipation	21.5% 34/158 • Number of events 46 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	39.8% 39/98 • Number of events 67 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Diarrhoea	43.7% 69/158 • Number of events 218 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	24.5% 24/98 • Number of events 33 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Dry mouth	38.6% 61/158 • Number of events 73 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 6 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Nausea	12.7% 20/158 • Number of events 26 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	43.9% 43/98 • Number of events 93 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Stomatitis	12.0% 19/158 • Number of events 28 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	9.2% 9/98 • Number of events 13 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Gastrointestinal disorders Vomiting	12.7% 20/158 • Number of events 38 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	23.5% 23/98 • Number of events 35 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Asthenia	12.7% 20/158 • Number of events 53 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	25.5% 25/98 • Number of events 73 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Chest pain	5.1% 8/158 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	13.3% 13/98 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Face oedema	7.6% 12/158 • Number of events 14 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	4.1% 4/98 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Fatigue	15.2% 24/158 • Number of events 40 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	26.5% 26/98 • Number of events 47 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Malaise	5.1% 8/158 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Oedema	5.7% 9/158 • Number of events 16 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	8.2% 8/98 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Oedema peripheral	25.9% 41/158 • Number of events 57 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	13.3% 13/98 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
General disorders Pyrexia	13.3% 21/158 • Number of events 39 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	22.4% 22/98 • Number of events 41 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Hepatobiliary disorders Hepatic function abnormal	6.3% 10/158 • Number of events 41 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Conjunctivitis	1.9% 3/158 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Covid-19	19.0% 30/158 • Number of events 34 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	18.4% 18/98 • Number of events 18 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Nasopharyngitis	5.7% 9/158 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Paronychia	5.7% 9/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Pneumonia	6.3% 10/158 • Number of events 14 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Upper respiratory tract infection	5.7% 9/158 • Number of events 12 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	3.1% 3/98 • Number of events 3 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Infections and infestations Urinary tract infection	8.9% 14/158 • Number of events 24 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	4.1% 4/98 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Alanine aminotransferase increased	60.1% 95/158 • Number of events 324 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	39.8% 39/98 • Number of events 108 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Aspartate aminotransferase increased	61.4% 97/158 • Number of events 322 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	39.8% 39/98 • Number of events 94 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Bilirubin conjugated increased	12.0% 19/158 • Number of events 54 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Blood alkaline phosphatase increased	12.7% 20/158 • Number of events 36 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	8.2% 8/98 • Number of events 12 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Blood bilirubin increased	37.3% 59/158 • Number of events 230 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Blood creatinine increased	22.8% 36/158 • Number of events 76 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	15.3% 15/98 • Number of events 38 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Blood thyroid stimulating hormone increased	6.3% 10/158 • Number of events 14 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Electrocardiogram qt prolonged	20.3% 32/158 • Number of events 58 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 1 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Gamma-glutamyltransferase increased	12.7% 20/158 • Number of events 56 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	10.2% 10/98 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Lymphocyte count decreased	4.4% 7/158 • Number of events 21 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 28 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Neutrophil count decreased	19.6% 31/158 • Number of events 126 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	25.5% 25/98 • Number of events 90 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Platelet count decreased	20.3% 32/158 • Number of events 92 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	18.4% 18/98 • Number of events 46 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Weight decreased	6.3% 10/158 • Number of events 31 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	9.2% 9/98 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations Weight increased	14.6% 23/158 • Number of events 44 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	7.1% 7/98 • Number of events 20 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Investigations White blood cell count decreased	20.3% 32/158 • Number of events 142 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	25.5% 25/98 • Number of events 72 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Decreased appetite	17.1% 27/158 • Number of events 35 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	33.7% 33/98 • Number of events 56 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hyperglycaemia	3.2% 5/158 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	9.2% 9/98 • Number of events 17 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hyperuricaemia	6.3% 10/158 • Number of events 15 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 20 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypoalbuminaemia	14.6% 23/158 • Number of events 63 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypocalcaemia	8.2% 13/158 • Number of events 34 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	0.00% 0/98 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypokalaemia	14.6% 23/158 • Number of events 33 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	8.2% 8/98 • Number of events 25 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypomagnesaemia	5.1% 8/158 • Number of events 24 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hyponatraemia	8.9% 14/158 • Number of events 47 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Metabolism and nutrition disorders Hypoproteinaemia	5.1% 8/158 • Number of events 24 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	3.1% 3/98 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Musculoskeletal and connective tissue disorders Arthralgia	10.8% 17/158 • Number of events 22 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	9.2% 9/98 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Musculoskeletal and connective tissue disorders Back pain	8.9% 14/158 • Number of events 22 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	12.2% 12/98 • Number of events 19 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Musculoskeletal and connective tissue disorders Myalgia	6.3% 10/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	7.1% 7/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Musculoskeletal and connective tissue disorders Pain in extremity	7.6% 12/158 • Number of events 16 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 8 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Dizziness	7.0% 11/158 • Number of events 12 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	8.2% 8/98 • Number of events 13 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Dysgeusia	5.1% 8/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	12.2% 12/98 • Number of events 22 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Nervous system disorders Headache	13.9% 22/158 • Number of events 30 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	10.2% 10/98 • Number of events 13 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Psychiatric disorders Insomnia	6.3% 10/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 5 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Cough	10.1% 16/158 • Number of events 19 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	15.3% 15/98 • Number of events 22 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.2% 5/158 • Number of events 9 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	14.3% 14/98 • Number of events 18 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/158 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.7% 9/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	4.1% 4/98 • Number of events 4 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Alopecia	7.0% 11/158 • Number of events 12 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 6 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Dermatitis	5.1% 8/158 • Number of events 11 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	1.0% 1/98 • Number of events 2 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Dry skin	5.1% 8/158 • Number of events 10 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	6.1% 6/98 • Number of events 6 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Pruritus	10.1% 16/158 • Number of events 27 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	22.4% 22/98 • Number of events 26 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Rash	22.2% 35/158 • Number of events 54 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	21.4% 21/98 • Number of events 30 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Skin and subcutaneous tissue disorders Rash maculo-papular	3.8% 6/158 • Number of events 16 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	5.1% 5/98 • Number of events 7 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").
Vascular disorders Hypertension	48.1% 76/158 • Number of events 167 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").	7.1% 7/98 • Number of events 18 • Baseline Up to 38 Months Safety population is defined as all participants who received study drug regardless of strata and as pre-specified, adverse events were collected for the TRT B treatment arm as a whole. Analysis of safety data will be based on the actual treatment a participant received on the first study treatment administration regardless of which treatment they were randomized to receive ("as treated").

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-595-5979

Email: ClinicalTrials.gov@lilly.com

Results disclosure agreements

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

Restriction type: GT60