Trial Outcomes & Findings for A Phase 1/2 Trial of Multiple Oral Doses of OPC-167832 for Uncomplicated Pulmonary Tuberculosis (NCT NCT03678688)

Last Updated: 2023-11-18

Results Overview

Bacterial load in sputum at each collection time point was measured by CFU counts on agar media culture. EBA was determined by the rate of decline per day in log10CFU/mL during the first 14 days of treatment. Change from baseline in log 10 CFU was calculated as post-baseline minus baseline. A larger EBA in positive direction indicates a better drug effect.

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

122 participants

Primary outcome timeframe

Baseline to Day 14

Results posted on

2023-11-18

Participant Flow

Participants took part in this study at two investigative sites in South Africa from 18 October 2018 to 11 March 2022.

Participants with uncomplicated, smear-positive, drug-susceptible pulmonary tuberculosis were enrolled in two stages. Stage 1: A total of 76 participants were randomized in 4 cohorts to receive either OPC-167832 10 milligrams (mg), 30 mg, 90 mg \& 3 mg or a combination of rifampicin, isoniazid, ethambutol, and pyrazinamide (RHEZ). Stage 2: A total of 46 participants were randomized in 4 groups to receive OPC-167832+delamanid, OPC-167832+bedaquilline (BDQ), OPC-167832+delamanid+BDQ or RHEZ.

Participant milestones

Participant milestones
Measure	Stage 1: 10 mg OPC-167832 Participants received OPC-167832, 10 milligrams (mg), orally, once daily (QD), from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Overall Study STARTED	14	14	17	14	17	14	14	14	4
Overall Study Efficacy Analysis Set/ MITT Set	14	11	14	14	15	11	11	12	4
Overall Study Safety Analysis Set	14	14	17	14	16	13	13	14	4
Overall Study Pharmacokinetic (PK) Analysis Set	14	14	17	14	11	13	13	14	4
Overall Study COMPLETED	14	14	14	13	16	10	9	11	4
Overall Study NOT COMPLETED	0	0	3	1	1	4	5	3	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.
Overall Study Reason not Specified	3	0	1	0	0	0
Overall Study Non-Covid Related Adverse Event	0	1	0	0	2	1
Overall Study Covid Related Adverse Event	0	0	0	3	1	1
Overall Study Physician Decision	0	0	0	1	0	0
Overall Study Withdrawal by Subject	0	0	0	0	2	1

Baseline Characteristics

A Phase 1/2 Trial of Multiple Oral Doses of OPC-167832 for Uncomplicated Pulmonary Tuberculosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=17 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=17 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.	Total n=122 Participants Total of all reporting groups
Age, Continuous	31.7 years STANDARD_DEVIATION 14.6 • n=5 Participants	34.9 years STANDARD_DEVIATION 12.8 • n=7 Participants	36.2 years STANDARD_DEVIATION 13.3 • n=5 Participants	37.2 years STANDARD_DEVIATION 15.6 • n=4 Participants	33.4 years STANDARD_DEVIATION 10.9 • n=21 Participants	34.1 years STANDARD_DEVIATION 9.9 • n=8 Participants	29.8 years STANDARD_DEVIATION 8.9 • n=8 Participants	30.1 years STANDARD_DEVIATION 8.2 • n=24 Participants	31.3 years STANDARD_DEVIATION 9.5 • n=42 Participants	33.4 years STANDARD_DEVIATION 11.9 • n=42 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	5 Participants n=21 Participants	2 Participants n=8 Participants	2 Participants n=8 Participants	4 Participants n=24 Participants	1 Participants n=42 Participants	38 Participants n=42 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants	10 Participants n=4 Participants	12 Participants n=21 Participants	12 Participants n=8 Participants	12 Participants n=8 Participants	10 Participants n=24 Participants	3 Participants n=42 Participants	84 Participants n=42 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	0 Participants n=42 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	12 Participants n=7 Participants	17 Participants n=5 Participants	14 Participants n=4 Participants	15 Participants n=21 Participants	14 Participants n=8 Participants	14 Participants n=8 Participants	14 Participants n=24 Participants	4 Participants n=42 Participants	118 Participants n=42 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	4 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	8 Participants n=5 Participants	7 Participants n=7 Participants	11 Participants n=5 Participants	6 Participants n=4 Participants	8 Participants n=21 Participants	7 Participants n=8 Participants	10 Participants n=8 Participants	9 Participants n=24 Participants	3 Participants n=42 Participants	69 Participants n=42 Participants
Race/Ethnicity, Customized Other	6 Participants n=5 Participants	7 Participants n=7 Participants	5 Participants n=5 Participants	8 Participants n=4 Participants	9 Participants n=21 Participants	7 Participants n=8 Participants	4 Participants n=8 Participants	5 Participants n=24 Participants	1 Participants n=42 Participants	52 Participants n=42 Participants
Race/Ethnicity, Customized White	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=8 Participants	0 Participants n=8 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants	1 Participants n=42 Participants

PRIMARY outcome

Timeframe: Baseline to Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=10 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=13 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=11 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=14 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)	-1.93 sputum log10CFU/mL Standard Error 0.98	-2.12 sputum log10CFU/mL Standard Error 1.01	-2.08 sputum log10CFU/mL Standard Error 0.75	-1.69 sputum log10CFU/mL Standard Error 1.15	-2.79 sputum log10CFU/mL Standard Error 0.96	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=17 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=13 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Maximum (Peak) Plasma Concentration (Cmax) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	20.7 nanogram per milliliter (ng/mL) Standard Deviation 6.92	53.7 nanogram per milliliter (ng/mL) Standard Deviation 9.16	128 nanogram per milliliter (ng/mL) Standard Deviation 50.5	391 nanogram per milliliter (ng/mL) Standard Deviation 116	157 nanogram per milliliter (ng/mL) Standard Deviation 44.1	154 nanogram per milliliter (ng/mL) Standard Deviation 39.6	140 nanogram per milliliter (ng/mL) Standard Deviation 41.2	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration. Overall number of participants analyzed is the number of participants with data available for analysis.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Cmax at Steady-state (Cmax,ss) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	28.2 ng/mL Standard Deviation 10.9	67.3 ng/mL Standard Deviation 11.9	190 ng/mL Standard Deviation 63.6	492 ng/mL Standard Deviation 99.8	208 ng/mL Standard Deviation 60.5	175 ng/mL Standard Deviation 31.3	183 ng/mL Standard Deviation 51.9	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=17 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=13 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Time to Cmax (Tmax) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	3.17 hours Interval 2.17 to 4.17	4.15 hours Interval 1.17 to 5.15	3.15 hours Interval 2.15 to 5.17	3.25 hours Interval 2.13 to 5.17	2.83 hours Interval 1.83 to 4.83	3.17 hours Interval 1.17 to 5.18	3.83 hours Interval 1.8 to 7.9	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Tmax of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	3.17 hours Interval 1.18 to 5.17	3.15 hours Interval 1.15 to 5.13	3.13 hours Interval 2.13 to 5.13	3.17 hours Interval 2.13 to 5.13	2.83 hours Interval 1.82 to 5.83	3.13 hours Interval 2.17 to 4.25	2.83 hours Interval 1.83 to 4.85	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=13 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=17 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=12 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Area Under the Concentration-Time Curve (AUC) From Time Zero to Time t (the Last Observable Concentration, Here t=24) (AUC0-24), for OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	178 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 65.1	569 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 102	1290 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 532	4050 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 1240	1450 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 392	1490 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 490	1420 nanogram.hour per milliliter (ng*h/mL) Standard Deviation 378	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: AUC Calculated Over the Dosing Interval at Steady-state (AUCτ) for OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	349 ng*h/mL Standard Deviation 143	874 ng*h/mL Standard Deviation 127	2490 ng*h/mL Standard Deviation 928	5690 ng*h/mL Standard Deviation 1010	2500 ng*h/mL Standard Deviation 709	2020 ng*h/mL Standard Deviation 563	2000 ng*h/mL Standard Deviation 730	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

T1/2,z is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. Half-life (T1/2) is determined in the terminal phase after drug administration, which is calculated from the relationship T1/2 = ln2/λz where λz is the terminal-phase slope obtainable from non-compartmental analysis (NCA). The values reported for this outcome measure (OM) are estimates and not actual observed data.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=9 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Terminal-phase Elimination Half-life (t1/2,z) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	22.3 hours Interval 10.3 to 36.7	15.3 hours Interval 9.2 to 22.5	14.2 hours Interval 5.6 to 29.1	14.4 hours Interval 9.8 to 30.1	14.4 hours Interval 13.3 to 20.4	14.7 hours Interval 6.2 to 22.1	11.2 hours Interval 6.8 to 19.1	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Apparent Clearance From Plasma at Steady-state (CLss/F) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	164 mL/minute (min) Standard Deviation 62.6	195 mL/minute (min) Standard Deviation 28.8	231 mL/minute (min) Standard Deviation 91.8	272 mL/minute (min) Standard Deviation 53.8	215 mL/minute (min) Standard Deviation 61.0	269 mL/minute (min) Standard Deviation 88.5	283 mL/minute (min) Standard Deviation 103	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Accumulation Ratio of Cmax (RCmax) for OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	1.39 ratio Standard Deviation 0.381	1.26 ratio Standard Deviation 0.167	1.56 ratio Standard Deviation 0.399	1.36 ratio Standard Deviation 0.362	1.34 ratio Standard Deviation 0.349	1.23 ratio Standard Deviation 0.191	1.30 ratio Standard Deviation 0.244	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=13 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Accumulation Ratio of AUC (RAUC) for OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	1.99 ratio Standard Deviation 0.550	1.60 ratio Standard Deviation 0.289	2.01 ratio Standard Deviation 0.565	1.55 ratio Standard Deviation 0.416	1.70 ratio Standard Deviation 0.378	1.47 ratio Standard Deviation 0.314	1.36 ratio Standard Deviation 0.237	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Cmax Normalized to Dose (Cmax/Dose) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	9.42 (ng/mL)/mg Standard Deviation 3.63	6.73 (ng/mL)/mg Standard Deviation 1.19	6.34 (ng/mL)/mg Standard Deviation 2.12	5.46 (ng/mL)/mg Standard Deviation 1.11	6.94 (ng/mL)/mg Standard Deviation 2.02	5.85 (ng/mL)/mg Standard Deviation 1.04	6.10 (ng/mL)/mg Standard Deviation 1.73	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=11 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUCτ Normalized to Dose (AUCτ/Dose) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)	116 (ng*h/mL)/mg Standard Deviation 47.6	87.4 (ng*h/mL)/mg Standard Deviation 12.7	82.8 (ng*h/mL)/mg Standard Deviation 30.9	63.3 (ng*h/mL)/mg Standard Deviation 11.2	83.5 (ng*h/mL)/mg Standard Deviation 23.6	67.2 (ng*h/mL)/mg Standard Deviation 18.8	66.5 (ng*h/mL)/mg Standard Deviation 24.3	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax of Delamanid	181 ng/mL Standard Deviation 41.8	198 ng/mL Standard Deviation 57.5	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax,ss of Delamanid	401 ng/mL Standard Deviation 102	442 ng/mL Standard Deviation 188	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of Delamanid	3.82 hours Interval 1.83 to 5.83	4.82 hours Interval 2.83 to 7.9	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of Delamanid	3.83 hours Interval 1.83 to 5.83	3.83 hours Interval 2.7 to 7.83	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=12 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUC0-24 of Delamanid	2140 ng.h/mL Standard Deviation 613	2440 ng.h/mL Standard Deviation 957	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUCτ of Delamanid	5460 ng*h/mL Standard Deviation 1620	5860 ng*h/mL Standard Deviation 2310	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

T1/2,z is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. Half-life (T1/2) is determined in the terminal phase after drug administration, which is calculated from the relationship T1/2 = ln2/λz where λz is the terminal-phase slope obtainable using the NCA method. The values reported for this OM are estimates and not actual observed data.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=9 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=9 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: T1/2,z of Delamanid	25.4 hours Interval 16.3 to 38.4	25.1 hours Interval 17.6 to 56.4	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: CLss/F of Delamanid From Plasma	983 mL/min Standard Deviation 264	966 mL/min Standard Deviation 330	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: RCmax of Delamanid	2.26 ratio Standard Deviation 0.647	2.19 ratio Standard Deviation 0.601	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: RAUC of Delamanid	2.69 ratio Standard Deviation 0.683	2.49 ratio Standard Deviation 0.897	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax/Dose of Delamanid	1.34 (ng/mL)/mg Standard Deviation 0.339	1.47 (ng/mL)/mg Standard Deviation 0.625	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUCτ/Dose of Delamanid	18.2 (ng*h/mL)/mg Standard Deviation 5.40	19.5 (ng*h/mL)/mg Standard Deviation 7.71	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=12 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax of Bedaquiline	5150 ng/mL Standard Deviation 1860	5750 ng/mL Standard Deviation 2320	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax,ss of Bedaquiline	5030 ng/mL Standard Deviation 1850	6080 ng/mL Standard Deviation 1660	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=12 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of Bedaquiline	5.17 hours Interval 4.13 to 8.15	4.83 hours Interval 3.82 to 7.9	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of Bedaquiline	5.17 hours Interval 3.15 to 5.2	4.85 hours Interval 4.83 to 5.82	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=12 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=13 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUC0-24 of Bedaquiline	44900 ng*h/mL Standard Deviation 12800	47000 ng*h/mL Standard Deviation 15600	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUCτ of Bedaquiline	55900 ng*h/mL Standard Deviation 16000	66000 ng*h/mL Standard Deviation 19200	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

T1/2,z is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. Half-life (T1/2) is determined in the terminal phase after drug administration, which is calculated from the relationship T1/2 = ln2/λz where λz is the terminal-phase slope obtainable using the NCA method. The values reported for this OM are estimates and not actual observed data. Hence, the value might not lie within the sampling timepoints provided in the timeframe.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=5 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=7 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: T1/2,z of Bedaquiline	NA hours Interval 14.4 to 139.7 For the parameter that was not reported, due to less than 50% of the subjects having enough data to estimate the parameter, the descriptive statistic was not determined and not reported.	81.1 hours Interval 54.2 to 155.4	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: CLss/F of BDQ From Plasma	140 mL/min Standard Deviation 85.9	109 mL/min Standard Deviation 31.4	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax/Dose of Bedaquiline	12.6 (ng/mL)/mg Standard Deviation 4.62	15.2 (ng/mL)/mg Standard Deviation 4.14	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUCτ/Dose of Bedaquiline	140 (ng*h/mL)/mg Standard Deviation 40.0	165 (ng*h/mL)/mg Standard Deviation 48.0	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP.

An AE is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were all AEs which started after the start of randomized study drug treatment or if the event was continuous from baseline and was serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=17 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=16 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Number of Participants With Treatment-emergent Adverse Events (AEs)	10 Participants	13 Participants	13 Participants	11 Participants	15 Participants	9 Participants	11 Participants	9 Participants	3 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP. Number analyzed is the number of participants with data available for analysis for each specified vital sign parameter.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=17 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=16 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=13 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values Heart Rate: > 120 beats per minute (bpm) and >= 15 bpm Change from Baseline	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values Diastolic Blood Pressure: < 50 mmHg and >= 15 mmHg Decrease from Baseline	0 Participants	1 Participants	2 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values Systolic Blood Pressure: < 90 mmHg and >= 20 mmHg Decrease from Baseline	1 Participants	3 Participants	2 Participants	2 Participants	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values Weight: >= 5% Increase from Baseline	3 Participants	4 Participants	2 Participants	1 Participants	9 Participants	0 Participants	5 Participants	2 Participants	2 Participants

PRIMARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP. Overall number of participants analyzed is the number of participants with data available for analysis.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=13 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=16 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=12 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters ST/T Morphology: Symmetrical T-wave Inversion	1 Participants	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters Rhythm: Ventricular Premature Beat	0 Participants	1 Participants	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters ST/T Morphology: Myocardial Ischemia	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline to Day 14

Population: MITT Analysis Set included randomized participants who were agar media culture positive at baseline (either at Day -2 or at Day -1, or both), received any dose of IMP, and had at least one post-baseline CFU count value. Overall number of participants analyzed is the number of participants with data available for analysis. As pre-specified in the protocol and SAP, for Stage 2 data for participants in RHEZ arm was not included in this analysis.

LAM is a key component of the M. tuberculosis cell wall and the decline of sputum LAM concentrations has been shown to correlate closely with CFU decreases in sputum counted on agar media during the first 14 days of TB treatment. Sputum LAM concentration at each collection time point was measured using MGIT system. Baseline LAM was calculated as the log 10 of the average from Day -2 and Day -1 and the change from baseline in log10 was calculated as post-baseline minus baseline for each parameter.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=13 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=15 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System Raw	-1.52 log10 LAM picograms (pg)/ml Standard Deviation 0.79	-1.41 log10 LAM picograms (pg)/ml Standard Deviation 0.75	-1.44 log10 LAM picograms (pg)/ml Standard Deviation 0.67	-1.35 log10 LAM picograms (pg)/ml Standard Deviation 0.76	-1.19 log10 LAM picograms (pg)/ml Standard Deviation 0.75	-1.93 log10 LAM picograms (pg)/ml Standard Deviation 1.22	-0.97 log10 LAM picograms (pg)/ml Standard Deviation 0.62	-2.06 log10 LAM picograms (pg)/ml Standard Deviation 1.03	—
Stage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System Processed	-1.43 log10 LAM picograms (pg)/ml Standard Deviation 1.07	-1.55 log10 LAM picograms (pg)/ml Standard Deviation 0.90	-1.40 log10 LAM picograms (pg)/ml Standard Deviation 0.77	-1.42 log10 LAM picograms (pg)/ml Standard Deviation 0.74	-1.05 log10 LAM picograms (pg)/ml Standard Deviation 0.61	-2.05 log10 LAM picograms (pg)/ml Standard Deviation 1.26	-0.87 log10 LAM picograms (pg)/ml Standard Deviation 0.66	-1.84 log10 LAM picograms (pg)/ml Standard Deviation 1.39	—

SECONDARY outcome

Timeframe: Day 1 to Day 14 of treatment period + 42 days of inoculation period (up to 56 days)

TTD is the time from start of inoculation of a sputum sample until a MGIT machine detects a positive signal during the 42-day incubation period. One TTD measurement, reported in days and hours was taken at each of the visits at Days -2, -1, 2, 4, 6, 8, 10, 12 and 14. TTD values were then calculated as "days + hours/24" to be used in deriving the analysis values of TTD. Each sample collected from Day -2 to Day 14 were inoculated for 42 days. Baseline TTD was derived using Day -2 and Day -1 MGIT culture with a pure positive result for Mycobacterium tuberculosis. Postbaseline TTD analysis values from Day 1 were derived based on the MGIT culture result as follows: If MGIT culture result was negative for MTB complex, TTD was set to 42 days; If the MGIT culture was pure positive for MTB, but the TTD took longer than 42 days, TTD was capped at 42 days.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=14 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=13 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=13 Participants Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=15 Participants Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=11 Participants Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=10 Participants Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System	4.28 days Standard Deviation 2.88	9.54 days Standard Deviation 13.63	18.15 days Standard Deviation 15.06	3.33 days Standard Deviation 2.74	7.44 days Standard Deviation 1.65	8.93 days Standard Deviation 10.31	5.33 days Standard Deviation 2.54	14.26 days Standard Deviation 13.57	—

SECONDARY outcome

Timeframe: Baseline to Day 14

Population: MITT Analysis Set included randomized participants who were agar media culture positive at baseline (either at Day -2 or at Day -1, or both), received any dose of IMP, and had at least one post-baseline CFU count value. Overall number analyzed is the number of participants with data available for analysis. As pre-specified in the protocol and SAP, for Stage 2 data for participants in RHEZ arm was not included in this analysis.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=8 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=9 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=7 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Change From Baseline in TB Bacterial Load in Sputum as a Measure of EBA	-2.17 Sputum log10 CFU/mL Standard Error 1.83	-1.97 Sputum log10 CFU/mL Standard Error 1.29	-2.73 Sputum log10 CFU/mL Standard Error 1.51	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 2 hours and 6 hours post-dose on Day 14

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=4 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Plasma Concentration of Rifampin 2 hours Post-dose	4020 ng/mL Standard Deviation 2450	—	—	—	—	—	—	—	—
Stage 2: Plasma Concentration of Rifampin 6 hours Post-dose	1880 ng/mL Standard Deviation 811	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 2 hours and 6 hours post-dose on Day 14

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 1: Plasma Concentration of Isoniazid 2 hours Post-dose	4.16 microgram per millilitre (ug/mL) Standard Deviation 1.45	—	—	—	—	—	—	—	—
Stage 1: Plasma Concentration of Isoniazid 6 hours Post-dose	1.58 microgram per millilitre (ug/mL) Standard Deviation 0.837	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration.

DM-6705 is a metabolite of delamanid.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax of DM-6705	10.3 ng/mL Standard Deviation 10.5	14.6 ng/mL Standard Deviation 11.6	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

DM-6705 is a metabolite of delamanid.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax,ss of DM-6705	84.0 ng/mL Standard Deviation 27.5	112 ng/mL Standard Deviation 51.9	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1; Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration. Number analyzed is the number of participants with data available for analysis at the specified time point.

DM-6705 is a metabolite of delamanid.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of DM-6705 Day 1	4.82 hours Interval 1.83 to 23.63	4.83 hours Interval 1.83 to 23.58	—	—	—	—	—	—	—
Stage 2: Tmax of DM-6705 Day 14	4.83 hours Interval 0.33 to 7.83	4.85 hours Interval 2.7 to 11.85	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1; Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

Population: PK Analysis Set included all participants who received at least one dose of IMP and had 1 quantifiable drug concentration. Overall number analyzed is the number of participants with data available for analysis. Number analyzed is the number of participants with data available for analysis at the specified time point.

DM-6705 is a metabolite of delamanid.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=12 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUC0-24 for DM-6705 Day 1	103 ng*h/mL Standard Deviation 54.2	166 ng*h/mL Standard Deviation 124	—	—	—	—	—	—	—
Stage 2: AUC0-24 for DM-6705 Day 14	1620 ng*h/mL Standard Deviation 458	1980 ng*h/mL Standard Deviation 850	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

T1/2,z is the time required to divide the plasma concentration by two after reaching pseudo-equilibrium, and not the time required to eliminate half the administered dose. Half-life (T1/2) was determined in the terminal phase after drug administration, which was calculated from the relationship T1/2 = ln2/λz where λz is the terminal-phase slope obtainable using the NCA method. The values reported for this OM are estimates and not actual observed data. Hence, the value might not lie within the sampling timepoints provided in the timeframe.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=5 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=4 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: T1/2,z of DM-6705	NA hours Interval 90.2 to 509.1 For the parameter that was not reported, due to less than 50% of the subjects having enough data to estimate the parameter, the descriptive statistic was not determined and not reported.	NA hours Interval 95.8 to 1219.9 For the parameter that was not reported, due to less than 50% of the subjects having enough data to estimate the parameter, the descriptive statistic was not determined and not reported.	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=12 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax of N-Desmethyl Bedaquiline	95.4 ng/mL Standard Deviation 44.7	88.2 ng/mL Standard Deviation 17.5	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Cmax,ss of N-Desmethyl Bedaquiline	489 ng/mL Standard Deviation 154	575 ng/mL Standard Deviation 112	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours (±15 minutes) postdose on Day 1; Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Tmax of N-Desmethyl Bedaquiline Day 1	23.93 hours Interval 6.17 to 24.05	11.86 hours Interval 7.82 to 23.88	—	—	—	—	—	—	—
Stage 2: Tmax of N-Desmethyl Bedaquiline Day 14	15.08 hours Interval 0.0 to 48.0	7.83 hours Interval 3.83 to 23.63	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1; Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72, 96, 120 and 144 hours postdose on Day 14

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=10 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: AUC0-24 for N-Desmethyl Bedaquiline Day 1	1380 ng*h/mL Standard Deviation 731	1410 ng*h/mL Standard Deviation 326	—	—	—	—	—	—	—
Stage 2: AUC0-24 for N-Desmethyl Bedaquiline Day 14	10100 ng*h/mL Standard Deviation 3080	11800 ng*h/mL Standard Deviation 1920	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP.

An AE is defined as any untoward medical occurrence in a clinical trial participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. TEAEs were all adverse events which started after the start of randomized study drug treatment or if the event was continuous from baseline and was serious, study drug-related, or resulted in death, discontinuation, interruption, or reduction of study therapy.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=13 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Number of Participants With TEAEs on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline	9 Participants	11 Participants	9 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=13 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=13 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=14 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline Heart Rate: > 120 bpm and >= 15 bpm change from baseline	0 Participants	1 Participants	0 Participants	—	—	—	—	—	—
Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline Systolic blood pressure: < 90 mmHg and >= 20 mmHg decrease from baseline	1 Participants	1 Participants	1 Participants	—	—	—	—	—	—
Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline Diastolic blood pressure: < 50 mmHg and >= 15 mmHg decrease from baseline	0 Participants	2 Participants	0 Participants	—	—	—	—	—	—
Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline Weight: >= 5% increase from baseline	0 Participants	5 Participants	2 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug to end of follow up period (up to 34 days)

Population: Safety Analysis Set included participants who were randomized and received any dose of IMP. Overall number of participants analyzed is the number of participants available for analysis.

Outcome measures

Outcome measures
Measure	Stage 1: 10 mg OPC-167832 n=11 Participants Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=11 Participants Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=12 Participants Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Stage 2: Number of Participants With Clinically Significant Changes in ECG Evaluations on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline Rhythm: Ventricular Premature Beat	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Stage 2: Number of Participants With Clinically Significant Changes in ECG Evaluations on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline ST/T Morphology: Myocardial Ischemia	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—
Stage 2: Number of Participants With Clinically Significant Changes in ECG Evaluations on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline ST/T Morphology: Symmetrical T-wave Inversion	0 Participants	0 Participants	0 Participants	—	—	—	—	—	—

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 1 and Day 14

Outcome measures

Outcome data not reported

Adverse Events

Stage 1: 10 mg OPC-167832

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Stage 1: 30 mg OPC-167832

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Stage 1: 90 mg OPC-167832

Serious events: 0 serious events

Other events: 13 other events

Deaths: 0 deaths

Stage 1: 3 mg OPC-167832

Serious events: 1 serious events

Other events: 10 other events

Deaths: 0 deaths

Stage 1: RHEZ

Serious events: 0 serious events

Other events: 15 other events

Deaths: 0 deaths

Stage 2: 30 mg OPC-167832 + 300 mg Delamanid

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Stage 2: 30 mg OPC-167832 + 400 mg BDQ

Serious events: 2 serious events

Other events: 11 other events

Deaths: 0 deaths

Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Stage 2: RHEZ

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Stage 1: 10 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=17 participants at risk Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=16 participants at risk Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid n=13 participants at risk Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 participants at risk Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 participants at risk Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 participants at risk Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Anal abscess	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.

Other adverse events

Other adverse events
Measure	Stage 1: 10 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 10 mg, orally, QD, from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 30 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 30 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 90 mg OPC-167832 n=17 participants at risk Participants received OPC-167832, 90 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: 3 mg OPC-167832 n=14 participants at risk Participants received OPC-167832, 3 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 1: RHEZ n=16 participants at risk Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD from Day 1 through Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid n=13 participants at risk Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg, orally, QD from Day 1 through Day 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 400 mg BDQ n=13 participants at risk Participants received OPC-167832, 30 mg, in combination with BDQ, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, QD, orally from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ n=14 participants at risk Participants received OPC-167832, 30 mg, in combination with delamanid, 300 mg and BDQ, 400 mg, orally, QD, from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. BDQ was then administered at a dose of 400 mg, orally, QD from Days 3 to 14. After Day 14, participants received RHEZ according to the local standard of care regimen up to Day 20.	Stage 2: RHEZ n=4 participants at risk Participants received a single dose of RHEZ (each tablet containing 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, QD, from Day 1 through Day 20.
Blood and lymphatic system disorders Anaemia	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Cardiac disorders Atrioventricular Block First Degree	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Cardiac disorders Ventricular Extrasystoles	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Ear and labyrinth disorders Ear Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Eye disorders Conjunctival Irritation	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	11.8% 2/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Eye disorders Eye Irritation	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Eye disorders Eye Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Eye disorders Eye Pruritus	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Abdominal Pain	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	12.5% 2/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Anorectal Discomfort	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Constipation	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Diarrhoea	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Dyspepsia	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Gastritis	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Gingival Bleeding	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Nausea	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	25.0% 1/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Toothache	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Vomiting	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	12.5% 2/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Catheter Site Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Chest Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Fatigue	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Injection Site Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Non-cardiac Chest Pain	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Pyrexia	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Vessel Puncture Site Haematoma	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Vessel Puncture Site Swelling	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Abscess Limb	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Fungal Skin Infection	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Hordeolum	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Lower Respiratory Tract Infection	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Periodontitis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Skin Infection	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Tinea Capitis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Tinea Versicolour	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Tonsillitis	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Upper Respiratory Tract Infection	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Injury, poisoning and procedural complications Arthropod Bite	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Investigations Alanine Aminotransferase Increased	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Investigations Blood Creatine Phosphokinase Increased	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Investigations Liver Function Test Increased	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Metabolism and nutrition disorders Decreased Appetite	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Arthralgia	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Back Pain	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Costochondritis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Muscle Spasms	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Myalgia	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	17.6% 3/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Pain in Extremity	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Dizziness	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	23.1% 3/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Headache	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	28.6% 4/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	11.8% 2/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	21.4% 3/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	12.5% 2/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	30.8% 4/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Neuropathy Peripheral	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Paraesthesia	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Somnolence	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Psychiatric disorders Insomnia	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Renal and urinary disorders Dysuria	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Reproductive system and breast disorders Dysmenorrhoea	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Haemoptysis	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	18.8% 3/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Nasal Congestion	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Oropharyngeal Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Pleuritic Pain	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Acne	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Dermatitis Acneiform	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Dermatitis Allergic	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Dermatitis Contact	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	5.9% 1/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Dry Skin	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Pruritus	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	35.7% 5/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	17.6% 3/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	37.5% 6/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	14.3% 2/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	25.0% 1/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Rash	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	25.0% 1/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Rash Pruritic	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Vascular disorders Hot Flush	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Vascular disorders Orthostatic Hypotension	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	6.2% 1/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Abdominal Pain Lower	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Abdominal Pain Upper	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Gastrointestinal disorders Abdominal Tenderness	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Carbuncle	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Covid-19	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Pharyngitis	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Infections and infestations Tooth Abscess	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Injury, poisoning and procedural complications Lower Limb Fracture	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Injury, poisoning and procedural complications Muscle Strain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Metabolism and nutrition disorders Hyperuricaemia	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	25.0% 1/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Musculoskeletal and connective tissue disorders Neck Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Nervous system disorders Muscle Contractions Involuntary	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Respiratory, thoracic and mediastinal disorders Throat Irritation	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Rash Maculo-papular	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.1% 1/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Skin and subcutaneous tissue disorders Rash Papular	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
Reproductive system and breast disorders Testicular Pain	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	7.7% 1/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.
General disorders Inflammation	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/17 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/16 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	15.4% 2/13 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/14 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.	0.00% 0/4 • From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2) Safety Analysis Set included participants who were randomized and received any dose of IMP.

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 Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.
Publication restrictions are in place

Restriction type: OTHER