CompletedNCT03678688Updated Nov 18, 2023Results posted

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

A Phase 1/2 interventional study of 10 mg OPC-167832 and 30 mg OPC-167832 in Pulmonary TB, sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc.. Completed at 3 sites in South Africa. Open to participants aged 18 Years to 64 Years. Per ClinicalTrials.gov, last updated 2023-11-18.

Sponsored by Otsuka Pharmaceutical Development & Commercialization, Inc. (part of Otsuka Holdings Co., Ltd.) · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 122
Allocation: Randomized
Ages: 18 Years to 64 Years
Sex: All

Study summary

This trial will evaluate the safety, tolerability, pharmacokinetics (PK), and efficacy of multiple oral doses of OPC-167832 in participants with uncomplicated, smear-positive, drug-susceptible pulmonary tuberculosis (TB).

Conditions studied

Pulmonary TB

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Tuberculosis, Pulmonary 340

In context

Tuberculosis, Pulmonary

340 studies on the registry are indexed under Tuberculosis, Pulmonary; 69 are open to participants now.

This study's enrollment of 122 is below the median of 150 across 243 interventional studies indexed under Tuberculosis, Pulmonary.

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Lead sponsor

Otsuka Pharmaceutical Development & Commercialization, Inc. is the lead sponsor of 293 studies on the registry; 18 are open to participants now.

Of its 105 completed or terminated interventional studies of FDA-regulated products, 70 (67%) have results posted.

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Who can participate

Ages eligible: 18 Years to 64 Years
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Able to provide written, informed consent prior to initiation of any trial-related procedures, and able, in the opinion of the investigator, to comply with all the requirements of the trial.
Male or female participants between 18 and 64 years of age (inclusive) at the screening visit.
Body mass index ≥ 16.0 and ≤ 32.0 kilograms per meters squared (kg/m\^2) (inclusive) at the screening visit.
Newly diagnosed, uncomplicated, drug-susceptible pulmonary TB.
Microscopy performed on a sputum smear at screening indicates presence of acid-fast bacilli (at least 1+).
Able to produce an adequate volume of sputum (approximately 10 millilitres (mL) or more estimated overnight production).
Female participants of childbearing potential must agree to use 2 different approved methods of birth control or remain abstinent throughout the participation in the trial and for 12 weeks after the last dose of trial treatment (investigational medicinal product (IMP) or RHEZ).
Male participants must agree to use 2 different approved methods of birth control or remain abstinent throughout the participation in the trial and for 12 weeks after the last dose of trial treatment (IMP or RHEZ).

Exclusion criteria

Exclusion Criteria:

Participants are known or suspected of having resistance to rifampicin, isoniazid, ethambutol, or pyrazinamide using any combination of Xpert Mycobacterium tuberculosis/Rifampin (MTB/RIF), line probe assay, culture, and/or epidemiologic history at screening.
Poor general condition where no delay in treatment can be tolerated or where immediate hospital admission is warranted.
Evidence of clinically significant metabolic (including ongoing or current hypokalemia), gastrointestinal, neurological, psychiatric, endocrine or liver (e.g., hepatitis B and C) disease; malignancy; or other abnormalities (other than the indication being studied).
History of or current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia or symptom strongly suggestive of such a problem (for example, syncope or palpitations), tachyarrhythmia or status after myocardial infarction.
Known bleeding disorders or family history of bleeding disorders.
Any diseases or conditions in which the use of delamanid, rifampicin, isoniazid, pyrazinamide, ethambutol, or Bedaquiline is contraindicated.
Any prior treatment for M. tuberculosis within the past 3 years.
Any treatment with a drug active against M. tuberculosis (e.g., quinolones) within the 3 months prior to screening.
Clinical evidence of severe extrapulmonary TB (e.g., miliary TB, abdominal TB, urogenital TB, osteoarthritic TB, TB meningitis).
Evidence of pulmonary silicosis, lung fibrosis, or other lung condition considered as severe by the investigator (other than TB). In particular any underlying condition that could interfere with the assessment of x-ray images, sputum collection, or interpretation of sputum findings, or otherwise compromise the subject's participation in the trial.
Any renal impairment characterized by serum creatinine clearance of \<60 millilitres per minute (mL/min), or hepatic impairment characterized by alanine transaminase, aspartate transaminase, or total bilirubin >1.5 x upper limit of normal (ULN) of the clinical laboratory reference range at screening.
For Stage 1, participants who are human immunodeficiency virus (HIV) positive are excluded. For Stage 2, participants with HIV co-infection who are on antiretroviral drugs during screening or with CD4 cell count \<500/ millimeters cubed (mm\^3) are excluded.
Changes in the electrocardiogram (ECG) such as QTcF >450 milliseconds (msec), atrioventricular block II or III, bi-fasicular block, at screening or current history of clinically significant ventricular arrhythmias. Other ECG changes if considered clinically significant by the investigator.
Participants receiving any of the prohibited medications within the specified periods or who would be likely to require prohibited concomitant therapy during the trial.
Female participants who are breast-feeding or who have a positive pregnancy test result prior to receiving the first dose of IMP or RHEZ on Day 1.
History of significant drug and/or alcohol abuse within 2 years prior to screening.
History of or current hepatitis or carriers of HBsAg and/or anti-HCV.
Positive urine or blood alcohol test and/or urine drug screen for substance abuse at screening (not including cannabinoids).
History of having taken an investigational drug within 30 days preceding trial entry (ie, prior to screening).
A history of difficulty in donating blood.
Donation of blood or plasma within 30 days prior to dosing.
Consumption of alcohol and/or grapefruit, grapefruit juice, Seville oranges, or Seville orange juice and related products within 72 hours prior to the first dose of IMP or RHEZ on Day 1.
History of serious mental disorders that, in the opinion of the investigator, would exclude the subject from participating in this trial.
Any known prior exposure to OPC-167832, delamanid or Bedaquiline.
Participants with significant medical comorbidities that in the opinion of the investigator, should not participate in the trial.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Sequential assignment
Masking: None (open label)
Enrollment: 122 participants (actual)

Study arms

Active comparator
Stage 1: RHEZ
Participants received a single dose of RHEZ (each tablet containing 150 milligrams (mg) rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol), orally, once daily (QD) from Day 1 through Day 20.
Drug: RHEZ
Experimental
Stage 1: 10 mg OPC-167832
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.
Drug: 10 mg OPC-167832
Experimental
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.
Drug: 30 mg OPC-167832
Experimental
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.
Drug: 90 mg OPC-167832
Experimental
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.
Drug: 3 mg OPC-167832
Experimental
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.
Drug: 30 mg OPC-167832 + 300 mg delamanid
Experimental
Stage 2: 30 mg OPC-167832 + 400 mg Bedaquiline (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.
Drug: 30 mg OPC-167832 + 400 mg BDQ
Experimental
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.
Drug: 30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQ
Active comparator
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.
Drug: RHEZ

Interventions

Drug10 mg OPC-167832
Once daily oral dose of 10 mg OPC-167832 from Day 1 through Day 14.
Drug30 mg OPC-167832
Once daily oral dose of 30 mg OPC-167832 from Day 1 through Day 14.
Drug90 mg OPC-167832
Once daily oral dose of 90 mg OPC-167832 from Day 1 through Day 14.
Drug3 mg OPC-167832
Once daily oral dose of 3 mg OPC-167832 from Day 1 through Day 14.
DrugRHEZ
RHEZ was used in both Stage 1 and Stage 2. Each tablet contains 150 mg rifampicin, 75 mg isoniazid, 400 mg pyrazinamide, and 275 mg ethambutol. Participants received a single-dose from Day 1 through Day 20. The total number of tablets per day was based on the pretreatment body weight: * Participants weighing 30 to 37 kg received 2 tablets per day * Participants weighing 38 to 54 kg received 3 tablets per day * Participants weighing 55 to 70 kg received 4 tablets per day * Participants weighing \> 70 kg received 5 tablets per day
Drug30 mg OPC-167832 + 300 mg delamanid
Drug pages: Quabodepistat · OPC-67683
Once daily oral dose of 30 mg OPC-167832 plus 300 mg delamanid from Day 1 through Day 14.
Drug30 mg OPC-167832 + 400 mg BDQ
Once daily oral dose of 30 mg OPC-167832 plus 400 mg BDQ from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. The dose of BDQ was 400 mg QD for Days 3 to 14.
Drug30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQ
Once daily oral dose of 30 mg OPC-167832 plus 300 mg delamanid plus 400 mg BDQ from Day 1 through Day 14. Participants received a loading dose of 700 mg BDQ on Day 1 and 500 mg on Day 2. The dose of BDQ was 400 mg QD for Days 3 to 14.

What researchers measure

Primary outcomes

Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)
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.
Time frame: Baseline to Day 14
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)
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
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)
Time frame: 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
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)
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 1 and Stage 2: Tmax of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)
Time frame: 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
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)
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
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)
Time frame: 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
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)
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.
Time frame: 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
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)
Time frame: 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
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)
Time frame: 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
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)
Time frame: 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
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)
Time frame: 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
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)
Time frame: 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
Stage 2: Cmax of Delamanid
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Cmax,ss of Delamanid
Time frame: 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
Stage 2: Tmax of Delamanid
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Tmax of Delamanid
Time frame: 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
Stage 2: AUC0-24 of Delamanid
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: AUCτ of Delamanid
Time frame: 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
Stage 2: T1/2,z of Delamanid
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.
Time frame: 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
Stage 2: CLss/F of Delamanid From Plasma
Time frame: 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
Stage 2: RCmax of Delamanid
Time frame: 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
Stage 2: RAUC of Delamanid
Time frame: 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
Stage 2: Cmax/Dose of Delamanid
Time frame: 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
Stage 2: AUCτ/Dose of Delamanid
Time frame: 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
Stage 2: Cmax of Bedaquiline
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Cmax,ss of Bedaquiline
Time frame: 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
Stage 2: Tmax of Bedaquiline
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Tmax of Bedaquiline
Time frame: 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
Stage 2: AUC0-24 of Bedaquiline
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: AUCτ of Bedaquiline
Time frame: 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
Stage 2: T1/2,z of Bedaquiline
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.
Time frame: 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
Stage 2: CLss/F of BDQ From Plasma
Time frame: 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
Stage 2: Cmax/Dose of Bedaquiline
Time frame: 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
Stage 2: AUCτ/Dose of Bedaquiline
Time frame: 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
Stage 1 and Stage 2: Number of Participants With Treatment-emergent Adverse Events (AEs)
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.
Time frame: From first dose of study drug to end of follow up period (up to 34 days)
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values
Time frame: From first dose of study drug to end of follow up period (up to 34 days)
Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Time frame: From first dose of study drug to end of follow up period (up to 34 days)

Secondary outcomes

Stage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System
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.
Time frame: Baseline to Day 14
Stage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System
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.
Time frame: Day 1 to Day 14 of treatment period + 42 days of inoculation period (up to 56 days)
Stage 2: Change From Baseline in TB Bacterial Load in Sputum as a Measure of EBA
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.
Time frame: Baseline to Day 14
Stage 2: Plasma Concentration of Rifampin
Time frame: 2 hours and 6 hours post-dose on Day 14
Stage 1: Plasma Concentration of Isoniazid
Time frame: 2 hours and 6 hours post-dose on Day 14
Stage 2: Cmax of DM-6705
DM-6705 is a metabolite of delamanid.
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Cmax,ss of DM-6705
DM-6705 is a metabolite of delamanid.
Time frame: 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
Stage 2: Tmax of DM-6705
DM-6705 is a metabolite of delamanid.
Time frame: 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
Stage 2: AUC0-24 for DM-6705
DM-6705 is a metabolite of delamanid.
Time frame: 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
Stage 2: T1/2,z of DM-6705
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.
Time frame: 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
Stage 2: Cmax of N-Desmethyl Bedaquiline
N-Desmethyl Bedaquiline is a metabolite of BDQ.
Time frame: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Cmax,ss of N-Desmethyl Bedaquiline
N-Desmethyl Bedaquiline is a metabolite of BDQ.
Time frame: 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
Stage 2: Tmax of N-Desmethyl Bedaquiline
N-Desmethyl Bedaquiline is a metabolite of BDQ.
Time frame: 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
Stage 2: AUC0-24 for N-Desmethyl Bedaquiline
N-Desmethyl Bedaquiline is a metabolite of BDQ.
Time frame: 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
Stage 2: Number of Participants With TEAEs on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline
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.
Time frame: From first dose of study drug to end of follow up period (up to 34 days)
Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline
Time frame: From first dose of study drug to end of follow up period (up to 34 days)
Stage 2: Number of Participants With Clinically Significant Changes in ECG Evaluations on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline
Time frame: From first dose of study drug to end of follow up period (up to 34 days)

Other outcomes

Correlation of QT Interval and Plasma Concentrations of OPC-167832 and/or Delamanid and/or Bedaquiline
Time frame: Day 1 and Day 14

Results

Posted Nov 18, 2023

Participant flow

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

Participant flow — Overall Study
Milestone	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ
Started	14	14	17	14	17	14	14	14	4
Efficacy analysis set/ mitt set	14	11	14	14	15	11	11	12	4
Safety analysis set	14	14	17	14	16	13	13	14	4
Pharmacokinetic (pk) analysis set	14	14	17	14	11	13	13	14	4
Completed	14	14	14	13	16	10	9	11	4
Not completed	0	0	3	1	1	4	5	3	0
Withdrew: Reason not specified	0	0	3	0	1	0	0	0	0
Withdrew: Non-covid related adverse event	0	0	0	1	0	0	2	1	0
Withdrew: Covid related adverse event	0	0	0	0	0	3	1	1	0
Withdrew: Physician decision	0	0	0	0	0	1	0	0	0
Withdrew: Withdrawal by subject	0	0	0	0	0	0	2	1	0

Outcome measures

PrimaryStage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)

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.

Time frame:: Baseline to Day 14
Reported as:: Mean · sputum log10CFU/mL

Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)
sputum log10CFU/mL	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ
Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)	-1.93 ± 0.98	-2.12 ± 1.01	-2.08 ± 0.75	-1.69 ± 1.15	-2.79 ± 0.96

Statistical analysis

Stage 1: 10 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.689 · 95% CI 0.485 to 0.939The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 1: 10 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.689 · 95% CI 0.467 to 0.911The confidence interval for the EBA ratio is estimated using Taylor's method.
Stage 1: 30 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.759 · 95% CI 0.517 to 1.051The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 1: 30 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.759 · 95% CI 0.497 to 1.020The confidence interval for the EBA ratio is estimated using Taylor's method.
Stage 1: 90 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.745 · 95% CI 0.567 to 0.973The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 1: 90 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.745 · 95% CI 0.547 to 0.943The confidence interval for the EBA ratio is estimated using Taylor's method.
Stage 1: 3 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.605 · 95% CI 0.353 to 0.896The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 1: 3 mg OPC-167832 vs Stage 1: RHEZ · Eba ratio: 0.605 · 95% CI 0.338 to 0.871The confidence interval for the EBA ratio is estimated using Taylor's method.

PrimaryStage 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)

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · nanogram per milliliter (ng/mL)

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)
nanogram per milliliter (ng/mL)	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 6.92	53.7 ± 9.16	128 ± 50.5	391 ± 116	157 ± 44.1	154 ± 39.6	140 ± 41.2

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · ng/mL

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)
ng/mL	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 10.9	67.3 ± 11.9	190 ± 63.6	492 ± 99.8	208 ± 60.5	175 ± 31.3	183 ± 51.9

PrimaryStage 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)

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Median · hours

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)
hours	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 (2.17 to 4.17)	4.15 (1.17 to 5.15)	3.15 (2.15 to 5.17)	3.25 (2.13 to 5.17)	2.83 (1.83 to 4.83)	3.17 (1.17 to 5.18)	3.83 (1.80 to 7.90)

PrimaryStage 1 and Stage 2: Tmax of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)

Time frame:: 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
Reported as:: Median · hours

Stage 1 and Stage 2: Tmax of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)
hours	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 (1.18 to 5.17)	3.15 (1.15 to 5.13)	3.13 (2.13 to 5.13)	3.17 (2.13 to 5.13)	2.83 (1.82 to 5.83)	3.13 (2.17 to 4.25)	2.83 (1.83 to 4.85)

PrimaryStage 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)

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · nanogram.hour per milliliter (ng*h/mL)

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)
nanogram.hour per milliliter (ng*h/mL)	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 65.1	569 ± 102	1290 ± 532	4050 ± 1240	1450 ± 392	1490 ± 490	1420 ± 378

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · ng*h/mL

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)
ng*h/mL	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 143	874 ± 127	2490 ± 928	5690 ± 1010	2500 ± 709	2020 ± 563	2000 ± 730

PrimaryStage 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)

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.

Time frame:: 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
Reported as:: Median · hours

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)
hours	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 (10.3 to 36.7)	15.3 (9.2 to 22.5)	14.2 (5.6 to 29.1)	14.4 (9.8 to 30.1)	14.4 (13.3 to 20.4)	14.7 (6.2 to 22.1)	11.2 (6.8 to 19.1)

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · mL/minute (min)

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)
mL/minute (min)	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 62.6	195 ± 28.8	231 ± 91.8	272 ± 53.8	215 ± 61.0	269 ± 88.5	283 ± 103

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · ratio

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)
ratio	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 0.381	1.26 ± 0.167	1.56 ± 0.399	1.36 ± 0.362	1.34 ± 0.349	1.23 ± 0.191	1.30 ± 0.244

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · ratio

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)
ratio	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 0.550	1.60 ± 0.289	2.01 ± 0.565	1.55 ± 0.416	1.70 ± 0.378	1.47 ± 0.314	1.36 ± 0.237

PrimaryStage 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)

Time frame:: 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
Reported as:: Mean · (ng/mL)/mg

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)
(ng/mL)/mg	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 3.63	6.73 ± 1.19	6.34 ± 2.12	5.46 ± 1.11	6.94 ± 2.02	5.85 ± 1.04	6.10 ± 1.73

PrimaryStage 2: AUCτ Normalized to Dose (AUCτ/Dose) of OPC-167832 When Administered Alone (Stage 1) and in Combination With Delamanid, and BDQ (Stage 2)

Time frame:: 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
Reported as:: Mean · (ng*h/mL)/mg

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)
(ng*h/mL)/mg	Stage 1: 3 mg OPC-167832	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
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 ± 47.6	87.4 ± 12.7	82.8 ± 30.9	63.3 ± 11.2	83.5 ± 23.6	67.2 ± 18.8	66.5 ± 24.3

PrimaryStage 2: Cmax of Delamanid

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng/mL

Stage 2: Cmax of Delamanid
ng/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax of Delamanid	181 ± 41.8	198 ± 57.5

PrimaryStage 2: Cmax,ss of Delamanid

Time frame:: 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
Reported as:: Mean · ng/mL

Stage 2: Cmax,ss of Delamanid
ng/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax,ss of Delamanid	401 ± 102	442 ± 188

PrimaryStage 2: Tmax of Delamanid

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Median · hours

Stage 2: Tmax of Delamanid
hours	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Tmax of Delamanid	3.82 (1.83 to 5.83)	4.82 (2.83 to 7.90)

PrimaryStage 2: Tmax of Delamanid

Time frame:: 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
Reported as:: Median · hours

Stage 2: Tmax of Delamanid
hours	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Tmax of Delamanid	3.83 (1.83 to 5.83)	3.83 (2.70 to 7.83)

PrimaryStage 2: AUC0-24 of Delamanid

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng.h/mL

Stage 2: AUC0-24 of Delamanid
ng.h/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUC0-24 of Delamanid	2140 ± 613	2440 ± 957

PrimaryStage 2: AUCτ of Delamanid

Time frame:: 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
Reported as:: Mean · ng*h/mL

Stage 2: AUCτ of Delamanid
ng*h/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUCτ of Delamanid	5460 ± 1620	5860 ± 2310

PrimaryStage 2: T1/2,z of Delamanid

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.

Time frame:: 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
Reported as:: Median · hours

Stage 2: T1/2,z of Delamanid
hours	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: T1/2,z of Delamanid	25.4 (16.3 to 38.4)	25.1 (17.6 to 56.4)

PrimaryStage 2: CLss/F of Delamanid From Plasma

Time frame:: 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
Reported as:: Mean · mL/min

Stage 2: CLss/F of Delamanid From Plasma
mL/min	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: CLss/F of Delamanid From Plasma	983 ± 264	966 ± 330

PrimaryStage 2: RCmax of Delamanid

Time frame:: 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
Reported as:: Mean · ratio

Stage 2: RCmax of Delamanid
ratio	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: RCmax of Delamanid	2.26 ± 0.647	2.19 ± 0.601

PrimaryStage 2: RAUC of Delamanid

Time frame:: 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
Reported as:: Mean · ratio

Stage 2: RAUC of Delamanid
ratio	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: RAUC of Delamanid	2.69 ± 0.683	2.49 ± 0.897

PrimaryStage 2: Cmax/Dose of Delamanid

Time frame:: 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
Reported as:: Mean · (ng/mL)/mg

Stage 2: Cmax/Dose of Delamanid
(ng/mL)/mg	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax/Dose of Delamanid	1.34 ± 0.339	1.47 ± 0.625

PrimaryStage 2: AUCτ/Dose of Delamanid

Time frame:: 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
Reported as:: Mean · (ng*h/mL)/mg

Stage 2: AUCτ/Dose of Delamanid
(ng*h/mL)/mg	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUCτ/Dose of Delamanid	18.2 ± 5.40	19.5 ± 7.71

PrimaryStage 2: Cmax of Bedaquiline

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng/mL

Stage 2: Cmax of Bedaquiline
ng/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax of Bedaquiline	5150 ± 1860	5750 ± 2320

PrimaryStage 2: Cmax,ss of Bedaquiline

Time frame:: 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
Reported as:: Mean · ng/mL

Stage 2: Cmax,ss of Bedaquiline
ng/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax,ss of Bedaquiline	5030 ± 1850	6080 ± 1660

PrimaryStage 2: Tmax of Bedaquiline

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Median · hours

Stage 2: Tmax of Bedaquiline
hours	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Tmax of Bedaquiline	5.17 (4.13 to 8.15)	4.83 (3.82 to 7.90)

PrimaryStage 2: Tmax of Bedaquiline

Time frame:: 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
Reported as:: Median · hours

Stage 2: Tmax of Bedaquiline
hours	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Tmax of Bedaquiline	5.17 (3.15 to 5.20)	4.85 (4.83 to 5.82)

PrimaryStage 2: AUC0-24 of Bedaquiline

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng*h/mL

Stage 2: AUC0-24 of Bedaquiline
ng*h/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUC0-24 of Bedaquiline	44900 ± 12800	47000 ± 15600

PrimaryStage 2: AUCτ of Bedaquiline

Time frame:: 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
Reported as:: Mean · ng*h/mL

Stage 2: AUCτ of Bedaquiline
ng*h/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUCτ of Bedaquiline	55900 ± 16000	66000 ± 19200

PrimaryStage 2: T1/2,z of Bedaquiline

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.

Time frame:: 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
Reported as:: Median · hours

Stage 2: T1/2,z of Bedaquiline
hours	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: T1/2,z of Bedaquiline	NA (14.4 to 139.7)	81.1 (54.2 to 155.4)

PrimaryStage 2: CLss/F of BDQ From Plasma

Time frame:: 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
Reported as:: Mean · mL/min

Stage 2: CLss/F of BDQ From Plasma
mL/min	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: CLss/F of BDQ From Plasma	140 ± 85.9	109 ± 31.4

PrimaryStage 2: Cmax/Dose of Bedaquiline

Time frame:: 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
Reported as:: Mean · (ng/mL)/mg

Stage 2: Cmax/Dose of Bedaquiline
(ng/mL)/mg	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax/Dose of Bedaquiline	12.6 ± 4.62	15.2 ± 4.14

PrimaryStage 2: AUCτ/Dose of Bedaquiline

Time frame:: 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
Reported as:: Mean · (ng*h/mL)/mg

Stage 2: AUCτ/Dose of Bedaquiline
(ng*h/mL)/mg	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: AUCτ/Dose of Bedaquiline	140 ± 40.0	165 ± 48.0

PrimaryStage 1 and Stage 2: Number of Participants With Treatment-emergent Adverse Events (AEs)

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.

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · Participants

Stage 1 and Stage 2: Number of Participants With Treatment-emergent Adverse Events (AEs)
Participants	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ
Stage 1 and Stage 2: Number of Participants With Treatment-emergent Adverse Events (AEs)	10	13	13	11	15	9	11	9	3

PrimaryStage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · Participants

Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Vital Sign Values
Participants	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ
Heart Rate: > 120 beats per minute (bpm) and >= 15 bpm Change from Baseline	1	1	0	1	1	0	1	0	0
Diastolic Blood Pressure: < 50 mmHg and >= 15 mmHg Decrease from Baseline	0	1	2	1	0	0	2	0	0
Systolic Blood Pressure: < 90 mmHg and >= 20 mmHg Decrease from Baseline	1	3	2	2	0	1	1	1	0
Weight: >= 5% Increase from Baseline	3	4	2	1	9	0	5	2	2

PrimaryStage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · Participants

Stage 1 and Stage 2: Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Parameters
Participants	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: RHEZ
Rhythm: Ventricular Premature Beat	0	1	1	1
ST/T Morphology: Myocardial Ischemia	2	0	0	0
ST/T Morphology: Symmetrical T-wave Inversion	1	0	1	1

SecondaryStage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System

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.

Time frame:: Baseline to Day 14
Reported as:: Mean · log10 LAM picograms (pg)/ml

Stage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System
log10 LAM picograms (pg)/ml	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Raw	-1.52 ± 0.79	-1.41 ± 0.75	-1.44 ± 0.67	-1.35 ± 0.76	-1.19 ± 0.75	-1.93 ± 1.22	-0.97 ± 0.62	-2.06 ± 1.03
Processed	-1.43 ± 1.07	-1.55 ± 0.90	-1.40 ± 0.77	-1.42 ± 0.74	-1.05 ± 0.61	-2.05 ± 1.26	-0.87 ± 0.66	-1.84 ± 1.39

SecondaryStage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System

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.

Time frame:: Day 1 to Day 14 of treatment period + 42 days of inoculation period (up to 56 days)
Reported as:: Mean · days

Stage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System
days	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System	4.28 ± 2.88	9.54 ± 13.63	18.15 ± 15.06	3.33 ± 2.74	7.44 ± 1.65	8.93 ± 10.31	5.33 ± 2.54	14.26 ± 13.57

SecondaryStage 2: Change From Baseline in TB Bacterial Load in Sputum as a Measure of EBA

Time frame:: Baseline to Day 14
Reported as:: Mean · Sputum log10 CFU/mL

Stage 2: Change From Baseline in TB Bacterial Load in Sputum as a Measure of EBA
Sputum log10 CFU/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Change From Baseline in TB Bacterial Load in Sputum as a Measure of EBA	-2.17 ± 1.83	-1.97 ± 1.29	-2.73 ± 1.51

Statistical analysis

Stage 2: 30 mg OPC-167832 + 300 mg Delamanid vs Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ · Eba ratio: 1.256 · 95% CI 0.626 to 3.175The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 2: 30 mg OPC-167832 + 300 mg Delamanid vs Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ · Eba ratio: 1.256 · 95% CI 0.362 to 2.151The confidence interval for the EBA ratio is estimated using Taylor's method.
Stage 2: 30 mg OPC-167832 + 400 mg BDQ vs Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ · Eba ratio: 1.385 · 95% CI 0.736 to 2.656The confidence interval for the EBA ratio is estimated using Fieller's method.
Stage 2: 30 mg OPC-167832 + 400 mg BDQ vs Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ · Eba ratio: 1.385 · 95% CI 0.564 to 2.206The confidence interval for the EBA ratio is estimated using Taylor's method.

SecondaryStage 2: Plasma Concentration of Rifampin

Time frame:: 2 hours and 6 hours post-dose on Day 14
Reported as:: Mean · ng/mL

Stage 2: Plasma Concentration of Rifampin
ng/mL	Stage 2: RHEZ
2 hours Post-dose	4020 ± 2450
6 hours Post-dose	1880 ± 811

SecondaryStage 1: Plasma Concentration of Isoniazid

Time frame:: 2 hours and 6 hours post-dose on Day 14
Reported as:: Mean · microgram per millilitre (ug/mL)

Stage 1: Plasma Concentration of Isoniazid
microgram per millilitre (ug/mL)	Stage 1: RHEZ
2 hours Post-dose	4.16 ± 1.45
6 hours Post-dose	1.58 ± 0.837

SecondaryStage 2: Cmax of DM-6705

DM-6705 is a metabolite of delamanid.

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng/mL

Stage 2: Cmax of DM-6705
ng/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax of DM-6705	10.3 ± 10.5	14.6 ± 11.6

SecondaryStage 2: Cmax,ss of DM-6705

DM-6705 is a metabolite of delamanid.

Time frame:: 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
Reported as:: Mean · ng/mL

Stage 2: Cmax,ss of DM-6705
ng/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax,ss of DM-6705	84.0 ± 27.5	112 ± 51.9

SecondaryStage 2: Tmax of DM-6705

DM-6705 is a metabolite of delamanid.

Time frame:: 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
Reported as:: Median · hours

Stage 2: Tmax of DM-6705
hours	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Day 1	4.82 (1.83 to 23.63)	4.83 (1.83 to 23.58)
Day 14	4.83 (0.33 to 7.83)	4.85 (2.70 to 11.85)

SecondaryStage 2: AUC0-24 for DM-6705

DM-6705 is a metabolite of delamanid.

Time frame:: 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
Reported as:: Mean · ng*h/mL

Stage 2: AUC0-24 for DM-6705
ng*h/mL	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Day 1	103 ± 54.2	166 ± 124
Day 14	1620 ± 458	1980 ± 850

SecondaryStage 2: T1/2,z of DM-6705

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.

Time frame:: 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
Reported as:: Median · hours

Stage 2: T1/2,z of DM-6705
hours	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: T1/2,z of DM-6705	NA (90.2 to 509.1)	NA (95.8 to 1219.9)

SecondaryStage 2: Cmax of N-Desmethyl Bedaquiline

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Time frame:: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Reported as:: Mean · ng/mL

Stage 2: Cmax of N-Desmethyl Bedaquiline
ng/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax of N-Desmethyl Bedaquiline	95.4 ± 44.7	88.2 ± 17.5

SecondaryStage 2: Cmax,ss of N-Desmethyl Bedaquiline

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Time frame:: 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
Reported as:: Mean · ng/mL

Stage 2: Cmax,ss of N-Desmethyl Bedaquiline
ng/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Cmax,ss of N-Desmethyl Bedaquiline	489 ± 154	575 ± 112

SecondaryStage 2: Tmax of N-Desmethyl Bedaquiline

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Time frame:: 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
Reported as:: Median · hours

Stage 2: Tmax of N-Desmethyl Bedaquiline
hours	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Day 1	23.93 (6.17 to 24.05)	11.86 (7.82 to 23.88)
Day 14	15.08 (0.00 to 48.0)	7.83 (3.83 to 23.63)

SecondaryStage 2: AUC0-24 for N-Desmethyl Bedaquiline

N-Desmethyl Bedaquiline is a metabolite of BDQ.

Time frame:: 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
Reported as:: Mean · ng*h/mL

Stage 2: AUC0-24 for N-Desmethyl Bedaquiline
ng*h/mL	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Day 1	1380 ± 731	1410 ± 326
Day 14	10100 ± 3080	11800 ± 1920

SecondaryStage 2: Number of Participants With TEAEs on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline

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.

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · Participants

Stage 2: Number of Participants With TEAEs on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline
Participants	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Stage 2: Number of Participants With TEAEs on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline	9	11	9

SecondaryStage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · Participants

Stage 2: Number of Participants With Clinically Significant Vital Sign Changes on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline
Participants	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Heart Rate: > 120 bpm and >= 15 bpm change from baseline	0	1	0
Diastolic blood pressure: < 50 mmHg and >= 15 mmHg decrease from baseline	0	2	0
Systolic blood pressure: < 90 mmHg and >= 20 mmHg decrease from baseline	1	1	1
Weight: >= 5% increase from baseline	0	5	2

SecondaryStage 2: Number of Participants With Clinically Significant Changes in ECG Evaluations on Administration of OPC-167832 in Combination With Delamanid and/or Bedaquiline

Time frame:: From first dose of study drug to end of follow up period (up to 34 days)
Reported as:: Count of participants · 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
Participants	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ
Rhythm: Ventricular Premature Beat	0	0	0
ST/T Morphology: Myocardial Ischemia	0	0	0
ST/T Morphology: Symmetrical T-wave Inversion	0	0	0

Other pre-specifiedCorrelation of QT Interval and Plasma Concentrations of OPC-167832 and/or Delamanid and/or Bedaquiline

Time frame:: Day 1 and Day 14

Results for this outcome have not been posted.

Adverse events

Collected over From first dose of study drug to end of follow up period (up to approximately 34 days in each Stage 1 and Stage 2). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Stage 1: 10 mg OPC-167832	0/14 (0%)	0/14 (0%)	10/14 (71.4%)
Stage 1: 30 mg OPC-167832	0/14 (0%)	0/14 (0%)	13/14 (92.9%)
Stage 1: 90 mg OPC-167832	0/17 (0%)	0/17 (0%)	13/17 (76.5%)
Stage 1: 3 mg OPC-167832	0/14 (0%)	1/14 (7.1%)	10/14 (71.4%)
Stage 1: RHEZ	0/16 (0%)	0/16 (0%)	15/16 (93.8%)
Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	0/13 (0%)	0/13 (0%)	9/13 (69.2%)
Stage 2: 30 mg OPC-167832 + 400 mg BDQ	0/13 (0%)	2/13 (15.4%)	11/13 (84.6%)
Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	0/14 (0%)	0/14 (0%)	9/14 (64.3%)
Stage 2: RHEZ	0/4 (0%)	0/4 (0%)	3/4 (75%)

Most frequent serious events

Most frequent serious events
Event	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ
Anal abscessInfections and infestations	0/14	0/14	0/17	0/14	0/16	0/13	1/13	0/14	0/4
PneumothoraxRespiratory, thoracic and mediastinal disorders	0/14	0/14	0/17	0/14	0/16	0/13	1/13	0/14	0/4
HaemoptysisRespiratory, thoracic and mediastinal disorders	0/14	0/14	0/17	1/14	0/16	0/13	0/13	0/14	0/4

Most frequent other events

Showing 10 of 93

Most frequent other events
Event	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ
PruritusSkin and subcutaneous tissue disorders	1/14	5/14	3/17	2/14	6/16	0/13	1/13	2/14	1/4
HeadacheNervous system disorders	3/14	4/14	2/17	3/14	2/16	2/13	4/13	1/14	0/4
NauseaGastrointestinal disorders	1/14	0/14	0/17	1/14	1/16	2/13	0/13	3/14	1/4
RashSkin and subcutaneous tissue disorders	0/14	1/14	0/17	0/14	1/16	1/13	1/13	0/14	1/4
HyperuricaemiaMetabolism and nutrition disorders	0/14	0/14	0/17	0/14	0/16	0/13	0/13	0/14	1/4
DizzinessNervous system disorders	1/14	1/14	0/17	1/14	1/16	0/13	3/13	1/14	0/4
Eye PainEye disorders	0/14	3/14	0/17	0/14	0/16	0/13	0/13	0/14	0/4
VomitingGastrointestinal disorders	2/14	2/14	0/17	0/14	2/16	1/13	0/13	3/14	0/4
Non-cardiac Chest PainGeneral disorders	3/14	0/14	0/17	0/14	0/16	0/13	0/13	0/14	0/4
HaemoptysisRespiratory, thoracic and mediastinal disorders	1/14	1/14	1/17	0/14	3/16	1/13	0/13	0/14	0/4

Baseline characteristics

Randomized Analysis Set included participants who were randomized into the trial.

Age, Continuous
Age, Continuous(years)	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ	Total
Mean	31.7 ± 14.6	34.9 ± 12.8	36.2 ± 13.3	37.2 ± 15.6	33.4 ± 10.9	34.1 ± 9.9	29.8 ± 8.9	30.1 ± 8.2	31.3 ± 9.5	33.4 ± 11.9

Sex: Female, Male
Sex: Female, Male(Participants)	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ	Total
Female	4	8	8	4	5	2	2	4	1	38
Male	10	6	9	10	12	12	12	10	3	84

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ	Total
Hispanic or Latino	0	0	0	0	0	0	0	0	0	0
Not Hispanic or Latino	14	12	17	14	15	14	14	14	4	118
Unknown or Not Reported	0	2	0	0	2	0	0	0	0	4

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Stage 1: 10 mg OPC-167832	Stage 1: 30 mg OPC-167832	Stage 1: 90 mg OPC-167832	Stage 1: 3 mg OPC-167832	Stage 1: RHEZ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid	Stage 2: 30 mg OPC-167832 + 400 mg BDQ	Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ	Stage 2: RHEZ	Total
Black or African American	8	7	11	6	8	7	10	9	3	69
Other	6	7	5	8	9	7	4	5	1	52
White	0	0	1	0	0	0	0	0	0	1

Study locations

3 sites

University of Cape Town (Pty) Ltd.
Cape Town, Mowbray 7700, South Africa
Satellite Site: Task at Brooklyn Chest Hospital
Cape Town, 7405, South Africa
TASK Clinical Research Centre
Cape Town, 7530, South Africa

References and documents

Publications

Shin E, Bhat AG, Ramanathan M. Large Language Models for Clinical Trial Protocol Assessments. Clin Pharmacol Ther. 2026 Feb;119(2):393-402. doi: 10.1002/cpt.70096. Epub 2025 Oct 21. PubMed 41121745 ↗
Dawson R, Diacon AH, De Jager V, Narunsky K, Moodley VM, Stinson KW, Liu Y, Zheng B, Hafkin J. Safety, pharmacokinetics, and early bactericidal activity of quabodepistat in combination with delamanid, bedaquiline, or both in adults with pulmonary tuberculosis: a randomised, active-controlled, open-label trial. Lancet Infect Dis. 2025 Apr;25(4):435-444. doi: 10.1016/S1473-3099(24)00601-7. Epub 2024 Nov 26. PubMed 39612928 ↗

Study documents

Study protocol · May 12, 2021
Statistical analysis plan · May 19, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Timeline

Tracking since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reached

Ran from Oct 2018 to primary completion in Feb 2022, 39 months.

Results were first posted in Nov 2023, 1 year 9 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered: Sep 18, 2018
First posted: Sep 20, 2018
StartActual: Oct 18, 2018
Primary completionActual: Feb 14, 2022
CompletionActual: Mar 11, 2022
Results first posted: Nov 18, 2023
Last update: Nov 18, 2023

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Nov 18, 2023, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03678688
Lead sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.
Collaborators: Bill and Melinda Gates Foundation
Responsible party: Sponsor
First posted: Sep 20, 2018
Start date: Oct 18, 2018
Primary completion: Feb 14, 2022
Completion: Mar 11, 2022
Results posted: Nov 18, 2023
Last update: Nov 18, 2023

Study contacts

Veronique R de Jager, MD

principal investigator · TASK Clinical Research Centre

Prof. Rodney Dawson, MD

principal investigator · University of Cape Town (Pty) Ltd.

Prof. Andreas Diacon

principal investigator · TASK Clinical Research Centre (TCRC)

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.

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Studies of the drugs tested here: Quabodepistat · OPC-67683

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Tuberculosis, Pulmonary →

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Otsuka Pharmaceutical Development & Commercialization, Inc. →

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

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