Trial Outcomes & Findings for To Investigate the Efficacy and Safety of OPC-6535 in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT00917150)

Last Updated: 2021-04-30

Results Overview

Measurement over time (from baseline over the 24-month treatment period) and change from baseline to end of the treatment period.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

771 participants

Primary outcome timeframe

Baseline, 24 months

Results posted on

2021-04-30

Participant Flow

Participant milestones

Participant milestones
Measure	OPC-6535 12.5 mg Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo Oral administration of placebo once daily for 24 months
Overall Study STARTED	192	198	191	190
Overall Study COMPLETED	155	161	149	156
Overall Study NOT COMPLETED	37	37	42	34

Reasons for withdrawal

Reasons for withdrawal
Measure	OPC-6535 12.5 mg Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo Oral administration of placebo once daily for 24 months
Overall Study Adverse Event	12	7	12	11
Overall Study Death	1	4	3	2
Overall Study Lost to Follow-up	1	0	4	2
Overall Study Physician Decision	0	2	0	1
Overall Study Protocol Violation	5	5	3	5
Overall Study Withdrawal by Subject	15	16	18	11
Overall Study Other than specified	3	3	2	2

Baseline Characteristics

To Investigate the Efficacy and Safety of OPC-6535 in Chronic Obstructive Pulmonary Disease (COPD) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	OPC-6535 12.5 mg n=192 Participants Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=198 Participants Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=191 Participants Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=190 Participants Oral administration of placebo once daily for 24 months	Total n=771 Participants Total of all reporting groups
Age, Continuous	62.2 years STANDARD_DEVIATION 7.63 • n=93 Participants	64.0 years STANDARD_DEVIATION 7.01 • n=4 Participants	63.2 years STANDARD_DEVIATION 7.55 • n=27 Participants	63.4 years STANDARD_DEVIATION 7.24 • n=483 Participants	63.2 years STANDARD_DEVIATION 7.37 • n=36 Participants
Sex: Female, Male Female	14 Participants n=93 Participants	7 Participants n=4 Participants	18 Participants n=27 Participants	15 Participants n=483 Participants	54 Participants n=36 Participants
Sex: Female, Male Male	178 Participants n=93 Participants	191 Participants n=4 Participants	173 Participants n=27 Participants	175 Participants n=483 Participants	717 Participants n=36 Participants
Region of Enrollment South Korea	32 Participants n=93 Participants	37 Participants n=4 Participants	35 Participants n=27 Participants	32 Participants n=483 Participants	136 Participants n=36 Participants
Region of Enrollment Japan	12 Participants n=93 Participants	13 Participants n=4 Participants	10 Participants n=27 Participants	10 Participants n=483 Participants	45 Participants n=36 Participants
Region of Enrollment China	148 Participants n=93 Participants	148 Participants n=4 Participants	146 Participants n=27 Participants	148 Participants n=483 Participants	590 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline, 24 months

Population: ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation.

Measurement over time (from baseline over the 24-month treatment period) and change from baseline to end of the treatment period.

Outcome measures

Outcome measures
Measure	OPC-6535 12.5 mg n=152 Participants Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=163 Participants Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=152 Participants Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=149 Participants Oral administration of placebo once daily for 24 months
Trough Forced Expiratory Volume in 1 Second (FEV1) Change From Baseline to 24 Months	-0.004 Liters Standard Error 0.0481	-0.023 Liters Standard Error 0.0481	-0.018 Liters Standard Error 0.0473	-0.035 Liters Standard Error 0.0480

SECONDARY outcome

Timeframe: Baseline, 24 months

Population: ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation.

Subjects were required to keep a symptom diary throughout the entire trial period from the start of investigational medicinal product (IMP) administration in the washout period until the end of the treatment period. Assessment items included scores for shortness of breath, cough, and sputum, IMP compliance, use of salbutamol and respiratory symptom medications, and smoking status. Subjects recorded a score of between 0 and 3, with 0 indicating no symptoms and 3 indicating a high level of symptoms, for each domain.

Outcome measures

Outcome measures
Measure	OPC-6535 12.5 mg n=150 Participants Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=161 Participants Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=152 Participants Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=151 Participants Oral administration of placebo once daily for 24 months
Change From Baseline at 24 Months in Total Symptom Diary Score	0.063 score on a scale Standard Error 0.0606	0.073 score on a scale Standard Error 0.0606	0.077 score on a scale Standard Error 0.0597	0.101 score on a scale Standard Error 0.0606

SECONDARY outcome

Timeframe: Baseline, 24 months

Population: ITT population consisted of all subjects randomized to double-blind therapy, regardless of any protocol violation.

The SGRQ is a self-administered questionnaire designed to measure and quantify the impact of chronic respiratory disease on health-related quality of life (QOL) and well-being in three domains: symptoms, activity, and impact on daily life. The SGRQ was completed by each subject prior to IMP administration at baseline and at Month 6, Month 12, Month 18, and Month 24 (end of treatment). A weighted score based on population norms for each dimension and total was evaluated. Scores were expressed as a percentage of overall impairment where 100 represented worst possible health status and 0 indicated best possible health status. Scores were calculated when less than 24% of the item scores were missing, otherwise the scores were set to missing. Where there were multiple answers for a question, the worst case was used.

Outcome measures

Outcome measures
Measure	OPC-6535 12.5 mg n=151 Participants Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=157 Participants Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=148 Participants Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=151 Participants Oral administration of placebo once daily for 24 months
Change From Baseline at 24 Months in St. George's Respiratory Questionnaire (SGRQ) Total Score	-9.6 score on a scale Standard Error 3.80	-7.9 score on a scale Standard Error 3.80	-7.7 score on a scale Standard Error 3.73	-10.4 score on a scale Standard Error 3.80

Adverse Events

OPC-6535 12.5 mg

Serious events: 47 serious events

Other events: 108 other events

Deaths: 1 deaths

OPC-6535 25 mg

Serious events: 47 serious events

Other events: 116 other events

Deaths: 5 deaths

OPC-6535 50 mg

Serious events: 50 serious events

Other events: 102 other events

Deaths: 3 deaths

Placebo

Serious events: 46 serious events

Other events: 105 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Director of Clinical Trials

Otsuka Pharmaceutical Co., LTD.

Phone: +81-3-6361-7366

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	OPC-6535 12.5 mg n=192 participants at risk Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=196 participants at risk Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=191 participants at risk Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=190 participants at risk Oral administration of placebo once daily for 24 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disorder	11.5% 22/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	12.2% 24/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	11.5% 22/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	12.6% 24/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.0% 2/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.5% 3/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Respiratory, thoracic and mediastinal disorders Hiccups	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pneumonia	3.6% 7/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Upper respiratory tract infection	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.51% 1/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pulmonary tuberculosis	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Sinusitis	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.51% 1/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Appendicitis	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Bronchitis	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Bronchopneumonia	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Cellulitis	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.51% 1/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Hepatitis C	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Herpes zoster	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Herpes zoster infection neurological	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Influenza	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Lobar pneumonia	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Lung infection	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Nasopharyngitis	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pneumonia bacterial	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pseudomembranous colitis	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pulmonary tuberculoma	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Septic shock	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.1% 2/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Astrocytoma malignant	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bone neoplasm	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Brain cancer metastatic	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Chronic myelomonocytic leukaemia	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Head and neck cancer	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic cancer metastatic	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large cell lung cancer stage IV	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Large intestine carcinoma	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neuroendocrine tumour	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.51% 1/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Prostate cancer	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Renal cell carcinoma	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.

Other adverse events
Measure	OPC-6535 12.5 mg n=192 participants at risk Oral administration of 12.5mg OPC-6535 once daily for 24 months	OPC-6535 25 mg n=196 participants at risk Oral administration of 25mg OPC-6535 once daily for 24 months	OPC-6535 50 mg n=191 participants at risk Oral administration of 50 mg OPC-6535 once daily for 24 months (started from 25 mg for the first 2 weeks and the dose was titrated to 50 mg from the third week)	Placebo n=190 participants at risk Oral administration of placebo once daily for 24 months
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	30.2% 58/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	34.2% 67/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	27.2% 52/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	30.0% 57/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Respiratory, thoracic and mediastinal disorders Productive cough	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.1% 8/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.6% 7/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.1% 6/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Nasopharyngitis	17.2% 33/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	10.7% 21/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	9.9% 19/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	11.6% 22/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Infections and infestations Pneumonia	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.51% 1/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Diarrhoea	4.7% 9/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	5.1% 10/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	9.4% 18/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.2% 8/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Abdominal pain upper	4.2% 8/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	5.6% 11/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	5.2% 10/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Gastritis	1.6% 3/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.6% 7/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.7% 9/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Abdominal distension	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.1% 6/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Abdominal discomfort	1.0% 2/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.5% 3/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.2% 8/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Toothache	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Nausea	1.6% 3/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Gastrooesophageal reflux disease	2.6% 5/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.5% 3/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Abdominal pain	0.00% 0/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.1% 6/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Gastrointestinal disorders Dyspepsia	1.0% 2/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Investigations Blood creatine phosphokinase increased	2.6% 5/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Investigations Protein urine present	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.52% 1/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.1% 2/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Musculoskeletal and connective tissue disorders Myalgia	1.0% 2/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.6% 7/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Nervous system disorders Headache	3.6% 7/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.1% 8/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Nervous system disorders Dizziness	1.0% 2/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	3.6% 7/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Metabolism and nutrition disorders Anorexia	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	5.2% 10/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Metabolism and nutrition disorders Hyperlipidaemia	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.00% 0/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.1% 2/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Cardiac disorders Angina pectoris	0.52% 1/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
General disorders Pyrexia	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.5% 3/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	0.53% 1/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Renal and urinary disorders Proteinuria	2.6% 5/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Vascular disorders Hypertension	2.1% 4/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	4.1% 8/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.6% 5/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Reproductive system and breast disorders Benign prostatic hyperplasia	3.1% 6/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.6% 3/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.
Blood and lymphatic system disorders Thrombocytopenia	4.2% 8/192 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.0% 4/196 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	1.0% 2/191 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.	2.1% 4/190 • Treatment-emergent adverse events (TEAEs) were collected from the start of IMP administration until follow-up (2 weeks after the end of treatment or early termination) Safety analyses were conducted on the safety population, defined all randomized subjects who took at least one dose of the IMP. A TEAE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of the IMP, regardless of judgment of relationship to the IMP.