Pulmonary TBPhase 1/2NCT03678688
A Phase 1/2 Trial of Multiple Oral Doses of OPC-167832 for Uncomplicated Pulmonary Tuberculosis
A Phase 1/2 study testing 10 mg OPC-167832, 30 mg OPC-167832 and 90 mg OPC-167832 in people with Pulmonary TB, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 3 sites in South Africa.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Pulmonary TB
- What is being tested?
- 10 mg OPC-167832, 30 mg OPC-167832 and 90 mg OPC-167832
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 122 participants
- Where
- 3 sitesSouth Africa
- Study dates
- 18 Oct 2018to 11 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
3 sites in 1 country.
South Africa3 sites
University of Cape Town (Pty) Ltd.
Cape Town, Mowbray, 7700
Satellite Site: Task at Brooklyn Chest Hospital
Cape Town, 7405
TASK Clinical Research Centre
Cape Town, 7530
About this study
Official title: A Phase 1/2, Active-controlled, Randomized, Open-label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Oral Doses of OPC-167832 Tablets in Subjects With Uncomplicated, Smear-positive, Drug-susceptible Pulmonary Tuberculosis
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
- Pulmonary TB
- Being tested
- 10 mg OPC-167832, 30 mg OPC-167832, 90 mg OPC-167832, 3 mg OPC-167832, RHEZ
- Medical subject headings
- Tuberculosis, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
10 mg OPC-167832Drug
Once daily oral dose of 10 mg OPC-167832 from Day 1 through Day 14.
30 mg OPC-167832Drug
Once daily oral dose of 30 mg OPC-167832 from Day 1 through Day 14.
90 mg OPC-167832Drug
Once daily oral dose of 90 mg OPC-167832 from Day 1 through Day 14.
3 mg OPC-167832Drug
Once daily oral dose of 3 mg OPC-167832 from Day 1 through Day 14.
RHEZDrug
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
30 mg OPC-167832 + 300 mg delamanidDrug
Once daily oral dose of 30 mg OPC-167832 plus 300 mg delamanid from Day 1 through Day 14.
30 mg OPC-167832 + 400 mg BDQDrug
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.
30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Stage 1: RHEZ | Active comparator | 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. Receives: Drug: RHEZ |
| Stage 1: 10 mg OPC-167832 | Experimental | 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. Receives: Drug: 10 mg OPC-167832 |
| Stage 1: 30 mg OPC-167832 | Experimental | 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. Receives: Drug: 30 mg OPC-167832 |
| Stage 1: 90 mg OPC-167832 | Experimental | 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. Receives: Drug: 90 mg OPC-167832 |
| Stage 1: 3 mg OPC-167832 | Experimental | 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. Receives: Drug: 3 mg OPC-167832 |
| Stage 2: 30 mg OPC-167832 + 300 mg Delamanid | Experimental | 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. Receives: Drug: 30 mg OPC-167832 + 300 mg delamanid |
| Stage 2: 30 mg OPC-167832 + 400 mg Bedaquiline (BDQ) | Experimental | 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. Receives: Drug: 30 mg OPC-167832 + 400 mg BDQ |
| Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ | Experimental | 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. Receives: Drug: 30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQ |
| Stage 2: RHEZ | Active comparator | 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. Receives: Drug: RHEZ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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.
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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)
Measured: 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
Measured: 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
Measured: 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
Measured: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Tmax of Delamanid
Measured: 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
Measured: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: AUCτ of Delamanid
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: Tmax of Bedaquiline
Measured: 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
Measured: Predose and 0.5, 1, 2, 3, 4, 5, 6, 8, 12, and 24 hours postdose on Day 1
Stage 2: AUCτ of Bedaquiline
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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
Measured: 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
Measured: From first dose of study drug to end of follow up period (up to 34 days)
Secondary outcomes (17)
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.
Measured: 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.
Measured: 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.
Measured: Baseline to Day 14
Stage 2: Plasma Concentration of Rifampin
Measured: 2 hours and 6 hours post-dose on Day 14
Stage 1: Plasma Concentration of Isoniazid
Measured: 2 hours and 6 hours post-dose on Day 14
Stage 2: Cmax of DM-6705
DM-6705 is a metabolite of delamanid.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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
Measured: From first dose of study drug to end of follow up period (up to 34 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2018
- Study start18 Oct 2018
- Primary completion14 Feb 2022
- Study completion11 Mar 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Pulmonary TBStudies of the same condition, open and under way.
- More trials run by Otsuka Pharmaceutical Development & Commercialization, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This will be a multiple-dose trial of OPC-167832 with 2 stages. Stage 1 is a multiple ascending dose trial planned to be conducted in 4 sequential cohorts of 18 participants each. There will be 2 arms (OPC-167832, combination of rifampicin, isoniazid, ethambutol, and pyrazinamide (RHEZ)) in each cohort. Stage 2 will be a parallel group comparison of 4 treatment regimens: 1) OPC-167832 plus Delamanid 2) OPC-167832 plus Bedaquiline 3) OPC-167832 plus Delamanid plus Bedaquiline 4) RHEZ.
- Masking
- None (open label)
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Bill and Melinda Gates Foundation
- Responsible party
- Sponsor
- Investigators
- Veronique R de Jager, MD, Principal investigator, TASK Clinical Research CentreProf. Rodney Dawson, MD, Principal investigator, University of Cape Town (Pty) Ltd.Prof. Andreas Diacon, Principal investigator, TASK Clinical Research Centre (TCRC)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03678688
- Sponsor's protocol ID
- 323-201-00003
- Other IDs
- OPP1178898
- Status last verified
- Oct 2023
- First submitted
- 18 Sep 2018
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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 41121745Dawson 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 at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/2, Active-controlled, Randomized, Open-label Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Oral Doses of OPC-167832 Tablets in Subjects With Uncomplicated, Smear-positive, Drug-susceptible Pulmonary Tuberculosis
- ClinicalTrials.gov ID
- NCT03678688
- Acronym / sponsor ID
- 323-201-00003
- Conditions
- Pulmonary TB
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Otsuka Pharmaceutical Development & Commercialization, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Bill and Melinda Gates Foundation
- Study start
- 18 Oct 2018 (actual)
- Primary completion
- 14 Feb 2022 (actual)
- Study completion
- 11 Mar 2022 (actual)
- First posted
- 20 Sep 2018 (actual)
- Results
- Posted 18 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 9
- Model description
- This will be a multiple-dose trial of OPC-167832 with 2 stages. Stage 1 is a multiple ascending dose trial planned to be conducted in 4 sequential cohorts of 18 participants each. There will be 2 arms (OPC-167832, combination of rifampicin, isoniazid, ethambutol, and pyrazinamide (RHEZ)) in each cohort. Stage 2 will be a parallel group comparison of 4 treatment regimens: 1) OPC-167832 plus Delamanid 2) OPC-167832 plus Bedaquiline 3) OPC-167832 plus Delamanid plus Bedaquiline 4) RHEZ.
| Arm | Type | Receives |
|---|---|---|
| Stage 1: RHEZ | Active comparator | Drug: RHEZParticipants 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. |
| Stage 1: 10 mg OPC-167832 | Experimental | Drug: 10 mg OPC-167832Participants 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 | Experimental | Drug: 30 mg OPC-167832Participants 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 | Experimental | Drug: 90 mg OPC-167832Participants 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 | Experimental | Drug: 3 mg OPC-167832Participants 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 2: 30 mg OPC-167832 + 300 mg Delamanid | Experimental | Drug: 30 mg OPC-167832 + 300 mg delamanidParticipants 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 Bedaquiline (BDQ) | Experimental | Drug: 30 mg OPC-167832 + 400 mg BDQParticipants 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 | Experimental | Drug: 30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQParticipants 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 | Active comparator | Drug: RHEZParticipants 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. |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- 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+).
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 10 mg OPC-167832Once daily oral dose of 10 mg OPC-167832 from Day 1 through Day 14. | Drug | Stage 1: 10 mg OPC-167832 |
| 30 mg OPC-167832Once daily oral dose of 30 mg OPC-167832 from Day 1 through Day 14. | Drug | Stage 1: 30 mg OPC-167832 |
| 90 mg OPC-167832Once daily oral dose of 90 mg OPC-167832 from Day 1 through Day 14. | Drug | Stage 1: 90 mg OPC-167832 |
| 3 mg OPC-167832Once daily oral dose of 3 mg OPC-167832 from Day 1 through Day 14. | Drug | Stage 1: 3 mg OPC-167832 |
| RHEZRHEZ 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 | Drug | Stage 1: RHEZ, Stage 2: RHEZ |
| 30 mg OPC-167832 + 300 mg delamanidOnce daily oral dose of 30 mg OPC-167832 plus 300 mg delamanid from Day 1 through Day 14. | Drug | Stage 2: 30 mg OPC-167832 + 300 mg Delamanid |
| 30 mg OPC-167832 + 400 mg BDQOnce 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. | Drug | Stage 2: 30 mg OPC-167832 + 400 mg Bedaquiline (BDQ) |
| 30 mg OPC-167832 + 300 mg delamanid + 400 mg BDQOnce 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. | Drug | Stage 2: 30 mg OPC-167832 + 300 mg Delamanid + 400 mg BDQ |
Primary outcome
Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA)
Time frame: Baseline to Day 14
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.
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)
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
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.
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
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
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.
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
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
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.
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)
Time frame: From first dose of study drug to end of follow up period (up to 34 days)
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.
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)
17 secondary outcomes
Stage 1 and Stage 2: Change From Baseline in Lipoarabinomannan (LAM) in the Mycobacteria Growth Indicator Tube® (MGIT) System
Time frame: Baseline to Day 14
Stage 1 and Stage 2: Change From Baseline in Time to Detection (TTD) in the MGIT System
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
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
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
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
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
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
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
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
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
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
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
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41121745Shin 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.
- Derived from this study: PubMed 39612928Dawson 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
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)
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 10 mg OPC-167832, 30 mg OPC-167832 and 90 mg OPC-167832 in people with Pulmonary TB, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 3 sites in South Africa.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Stage 1: Change From Baseline in TB Bacterial Load in Sputum as a Measure of Early Bactericidal Activity (EBA) (time frame: Baseline to Day 14). The study lists 38 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03678688, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.