Pulmonary TBPhase 2NCT05221502

Safety and Efficacy Evaluation of 4-month Regimen of OPC-167832, Delamanid and Bedaquiline in Participants With Drug-Susceptible Pulmonary TB

A Phase 2 study testing Delamanid, Bedaquiline and RHEZ in people with Pulmonary TB, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 6 sites in South Africa.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This trial will assess the safety and efficacy of OPC-167832 combined with delamanid and bedaquiline in participants with drug-susceptible tuberculosis (DS-TB) administered for 17 weeks compared to rifampin, isoniazid, ethambutol, pyrazinamide (RHEZ) administered for 26 weeks. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Pulmonary TB
What is being tested?: Delamanid, Bedaquiline and RHEZ
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 122 participants
Where: 6 sitesSouth Africa
Study dates: 12 Apr 2022to 19 May 2024
Phase: Phase 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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Able to provide written, informed consent prior to initiation of any trial-related procedures or treatments, and able, in the opinion of the investigator, to comply with all the requirements of the trial.
Male or female participants between 18 and 65 years of age (inclusive) at the screening visit.
Body weight ≥ 35.0 kg at the screening visit.
Newly diagnosed, rifampin and isoniazid susceptible (on the screening sample) pulmonary TB.
Able to spontaneously produce sputum.
Females of childbearing potential (FOCBP) must agree to use 2 different approved methods of birth control or remain abstinent throughout their participation in the trial and for 12 weeks after the last dose of IMP or dose of RHEZ.
Male participants must agree to use 2 different approved methods of birth control or remain abstinent throughout their participation in the trial and for 12 weeks after the last dose of IMP or RHEZ.

Who cannot join

Participants are known or suspected of having resistance to rifampin, isoniazid, ethambutol, pyrazinamide, DLM, or BDQ either confirmed by the laboratory, or based on epidemiological history, at screening.
Evidence of clinically significant metabolic (for example, including ongoing or current hypokalemia [ie, potassium <3.5 mEq/dL at screening]), gastrointestinal, neurological, psychiatric, endocrine or liver (eg, 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, uncontrolled 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 DLM, BDQ, OPC 167832, rifampin, isoniazid, pyrazinamide, or ethambutol is contraindicated.
Any prior treatment for M tuberculosis within the past 2 years.

Show all 26Show fewer

Any treatment with a drug active against M tuberculosis (eg, quinolones) within the 3 months prior to screening.
Clinical evidence of severe extrapulmonary TB (eg, 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 creatinine clearance/estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2, or hepatic impairment characterized by alanine transaminase or aspartate transaminase > 2.0 × upper limit of normal of the clinical laboratory reference range or bilirubin > 2.0 × upper limit of normal of the clinical laboratory reference range, at screening.
Screening glucose (nonfasting) ≥ 200 mg/dL or glycosylated hemoglobin (HbA1c) ≥ 6.5%.
QTcF > 450 msec in male participants (> 470 msec in female participants), atrioventricular block II or III, bi-fasicular block, at screening or current or history of clinically significant ventricular arrhythmias. Other ECG abnormalities, if considered clinically significant by the investigator.
Participants receiving any of the prohibited medications (see Section 6.5.1) 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.
Current history of significant drug and/or alcohol abuse that is likely to result in poor adherence to trial requirements or that would pose a risk to the participant's well-being during the course of the trial.
History of current hepatitis or carriers of hepatitis B surface antigen (HBsAg) and/or anti hepatitis C virus (HCV).
Participants who test positive for cocaine or other drugs of abuse (excluding known prescription stimulants and other prescribed medications and marijuana) at screening are excluded. Detectable levels of alcohol, marijuana, barbiturates, or opiates in the drug screen are not exclusionary if, in the investigator's documented opinion, the participant does not meet Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for moderate to severe substance use disorder and the positive test does not signal a clinical condition that would impact the safety of the participant or interpretation of the trial results, and participation is agreed to by the medical monitor prior to treatment.
History of having taken an investigational drug within 30 days preceding trial entry.
A history of difficulty in donating blood.
Donation of blood or plasma within 30 days prior to dosing.
History of serious mental disorders that, in the opinion of the investigator, would exclude the participant from participating in this trial.
Any known prior exposure to OPC-167832, DLM, or BDQ.
Participants with significant medical comorbidities that in the opinion of the investigator, should not participate in the trial.
Participants with Karnofsky score < 60 will be excluded from the trial.
Participants testing positive for active severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection at screening.
Participants with HIV co infection not on a stable anti-retroviral regimen consisting of tenofovir, emtricitabine/ lamivudine, dolutegravir (ie > 3 months), or who have a detectable viral load, or who have a CD4 count < 350 cells/mm3 will be excluded from the trial.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

South Africa6 sites

TASK Applied Science, Brooklyn Chest Hospital Premises
Cape Town, 7100
University of CapeTown Lung Center Institute
Cape Town, 7700
Themba Lethu Clinic Clinical HIV Research Unit (CHRU)
Johannesburg, 2092
Perinatal HIV Research Unit Tshepong Hospital Complex
Klerksdorp, 2574
Setshaba Research Center
Pretoria, 0152
Aurum Institute - Tembisa Clinical Research Centre
Tembisa, Gauteng, 1632

Other trials in South Africa

About this study

Official title: A Multicenter, Phase 2b/c, Open-label, Randomized, Dose-finding Trial to Evaluate the Safety and Efficacy of a 4 Month Regimen of OPC-167832 in Combination With Delamanid and Bedaquiline in Subjects With Drug-susceptible Pulmonary Tuberculosis in Comparison With Standard Treatment

Read the detailed description

Eligible participants for this study have a diagnosis of pulmonary DS-TB.

This is a Phase 2b/c multicenter, open-label, randomized, dose-finding study, consisting of up to 26 weeks of treatment period.

Following a screening period of up to 14 days, eligible participants will be randomized in the study.

Randomization will be stratified by presence of bilateral cavitation on screening chest x-ray (yes or no). After the end of the treatment period, participants will be followed until 12 months post randomization.

Conditions: Pulmonary TB
Being tested: Delamanid, Bedaquiline, RHEZ, Rifampin, Isoniazid
Medical subject headings: Tuberculosis, Pulmonary

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DelamanidDrug
Delamanid (300 mg QD) for 17 weeks
BedaquilineDrug
Bedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks
RHEZDrug
Also called RIFAFOUR
RHEZ (RIFAFOUR single dose combination tablets) for 8 weeks
RifampinDrug
Rifampin tablets for 18 weeks
IsoniazidDrug
Isoniazid tablets for 18 weeks
OPC-167832 10 mgDrug
OPC-167832 (10 mg QD) for 17 weeks
OPC-167832 30 mgDrug
OPC-167832 (30 mg QD) for 17 weeks
OPC-167832 90 mgDrug
OPC-167832 (90 mg QD) for 17 weeks

Study groups in NCT05221502
Study group	Role	What they receive
Delamanid + Bedaquiline + OPC-167832 10 mg	Experimental	Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, once daily (QD), bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, thrice weekly (TIW) and OPC-167832, 10 mg, oral tablets, QD for a total of 17 weeks. Receives: Drug: Delamanid; Drug: Bedaquiline; Drug: OPC-167832 10 mg
Delamanid + Bedaquiline + OPC-167832 30 mg	Experimental	Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 30 mg, oral tablets, QD for a total of 17 weeks. Receives: Drug: Delamanid; Drug: Bedaquiline; Drug: OPC-167832 30 mg
Delamanid + Bedaquiline + OPC-167832 90 mg	Experimental	Participants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 90 mg, oral tablets, QD for a total of 17 weeks. Receives: Drug: Delamanid; Drug: Bedaquiline; Drug: OPC-167832 90 mg
Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)	Active comparator	Participants will receive RHEZ, orally, QD for 8 weeks followed by 18 weeks of rifampin and isoniazid for a total of 26 weeks. Receives: Drug: RHEZ; Drug: Rifampin; Drug: Isoniazid

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment. Serious AE are AEs that leads to death, is life threatening, requires or prolongs hospitalization, significant disability, congenital anomaly or birth defect, and other medically important serious advent.
AEs were graded on a severity 3-point scale as follows: Mild: Discomfort noticed, but no disruption to daily activity.; Moderate: Discomfort sufficient to reduce or affect normal daily activity.;Severe: Inability to work or perform normal daily activity. As pre-specified in statistical analysis plan (SAP),Division of AIDS (DAIDS v2.1) criteria was used and AEs graded as follows:Grade 1-Mild;Grade 2-Moderate;Grade 3-Severe;Grade 4-Life Threatening;Grade 5-Death.
Measured: From first dose of study drug up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities
Laboratory assessments included clinical chemistry (Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Calcium, Creatinine, estimated Glomerular Filtration Rate (eGFR), Glucose, Fasting and Non-Fasting, Cholesterol, Inorganic Phosphorus, Magnesium, Potassium, Sodium, Triglycerides and Uric Acid), hematology (Activated Partial Thromboplastin Time, Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio (INR), Absolute CD4+ Count, Absolute Lymphocytes, Absolute Neutrophil Count, Hemoglobin, Platelet Count, White Blood Cell), and urinalysis (Urine Glucose, Blood and Protein). As pre-specified in statistical analysis plan (SAP), Division of AIDS (DAIDS) criteria was used and abnormalities were graded as follows:Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death. Laboratory values with DAIDS Grade ≥3 were considered as potentially clinically relevant abnormalities and are reported here.
Measured: Baseline up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Abnormalities in the Vital Signs
Vital signs measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body weight, and body temperature. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and sitting positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per DAIDS criteria pre-specified in SAP. Each vital sign parameter was graded using the DAIDS criteria as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Potentially Life Threatening; Grade 5 - Death. The categories with at least one participant with clinically significant value of any grade for vital signs are reported here.
Measured: Baseline up to end of follow up period (up to Week 52)
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities
3 ECGs were performed at baseline (Day -1) spaced 5 to 10 minutes apart, and 3 ECGs at all subsequent visits during the treatment and follow-up periods. The categories with at least one participant with clinically relevant ECG abnormalities are reported here.
Measured: Baseline up to end of follow up period (up to Week 52)
Number of Participants With an AE Reported as DAIDS Grade 3 or Higher
An AE was defined as any untoward medical occurrence in a clinical trial participant administered a treatment that does not necessarily have a causal relationship with the treatment. All AEs were graded on a 5-point scale according to DAIDS Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death.
Measured: From first dose of study drug up to end of follow up period (up to approximately Week 52)
Number of Participants With TEAEs Leading to Discontinuation of Treatment
An AE was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment.
Measured: From first dose of the study drug up to end of follow up period (up to approximately Week 52)
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) by End of Treatment (Week 17)
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% confidence interval (CI) was calculated using Clopper Pearson (exact) confidence interval model.
Measured: Week 17
Percentage of Participants Who Achieved SCC in MGIT by End of Treatment (Week 26)
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.
Measured: Week 26

Secondary outcomes (5)

Percentage of Participants Who Achieved SCC in MGIT by the End of 8 Weeks of Treatment
A participant was classified as having achieved SCC if he/she achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the 8 weeks of treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.
Measured: Week 8
Time to Detection of MGIT Cultures
Time to detection of MGIT cultures was the time assessed, in days, when a sputum culture result was positive using the MGIT system during the routine 42-day incubation period. A longer time to detection represented a lower burden of mycobacterium tuberculosis (MTB) organisms present in the sputum.
Measured: Baseline up to Week 52
Percentage of Participants Achieving Negative Sputum Lipoarabinomannan (LAM) by 8 Weeks of Treatment and by End of Treatment
Sputum LAM concentrations were measured on up to 3 samples collected at baseline and postbaseline at Week 8 and at end of treatment. A participant was classified as having achieved negative sputum conversion in LAM if the participant has the first of 2 visits of at least 1 week apart with sputum LAM negative (below the lower limit of quantification) and without a positive sputum LAM result in between. Numeric sputum LAM concentration data was converted to a binary variable using the rule: if the sputum LAM concentration was less than 10 picograms per milliliter (pg/mL) then it was interpreted as a negative result. If the sputum LAM concentration was greater than or equal to 10 pg/mL then it was interpreted as positive result. SCC for LAM was considered to have been achieved if there were negative results at two consecutive visits with non-missing results. 95% CI was calculated using Clopper Pearson (exact) confidence interval model.
Measured: Week 8, and End of Treatment Period - Week 17 (for OPC-167832 arms) and Week 26 (for RHEZ arm)
Percentage of Participants With Acquired Drug Resistance
Acquired resistance was defined as a post-baseline resistant result at any timepoint after a baseline susceptible result. Baseline was defined as Day -1, if Day -1 was missing then Day 1 was used, if day 1 was missing then Week 1 was used. Resistance data was collected for streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, bedaquiline and delamanid. Susceptibility testing (DST) for anti-TB medications was performed on positive M tuberculosis isolates from Day -1 or Day 1 cultures, and on the end of treatment sputum specimen. Percentage of participants who were susceptible at baseline and developed resistance to the indicated drug (class) at any post-baseline visits was summarized.
Measured: Baseline up to Week 52
Time to Sputum Culture Conversion (SCC)
Sputum culture conversion occurs when a participant has the first of 2 consecutive visits of at least 7 days apart with sputum cultures negative and without a positive sputum culture result in between, as well as no positive sputum culture after the negative results. If a participant had a positive MGIT culture result throughout the study period, then the participant was considered as not having achieved SCC within the period under consideration. The time to SCC in this case was censored. Time to SCC was calculated from date of first dose using MGIT cultures without the mitigation method measures.
Measured: From the first dose of the study up to the end of the follow-up period (up to Week 52)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Apr 202219 May 2024

First posted3 Feb 2022
Study start12 Apr 2022
Primary completion8 Apr 2024
Study completion19 May 2024

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 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 122 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05221502
Sponsor's protocol ID: 323-201-00006
Status last verified: Jul 2026
First submitted: 20 Aug 2021
Last updated: 12 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

Publications

Dawson R, Diacon AH, Variava E, Moloantoa T, Brumskine W, Ngwanto T, Zuma-Gwala N, Osman A, Rassool M, Bennet JA, Liu Y, Xu R, Li W, Takuva S, Hafkin J. Efficacy and safety of a 4-month quabodepistat, delamanid, and bedaquiline regimen for drug-susceptible pulmonary tuberculosis: a multicentre, open-label, randomised, proof-of-concept, non-inferiority, phase 2b/c trial. Lancet Infect Dis. 2026 May 29:S1473-3099(26)00143-X. doi: 10.1016/S1473-3099(26)00143-X. Online ahead of print.
PubMed 42214407
Dawson R, Diacon AH, Takuva S, Liu Y, Zheng B, Karwe V, Hafkin J. Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy. Trials. 2024 Jan 19;25(1):70. doi: 10.1186/s13063-024-07912-5.
PubMed 38243296

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Not yet recruitingPhase 2
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All Pulmonary TB trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Multicenter, Phase 2b/c, Open-label, Randomized, Dose-finding Trial to Evaluate the Safety and Efficacy of a 4 Month Regimen of OPC-167832 in Combination With Delamanid and Bedaquiline in Subjects With Drug-susceptible Pulmonary Tuberculosis in Comparison With Standard Treatment
ClinicalTrials.gov ID: NCT05221502
Acronym / sponsor ID: 323-201-00006
Conditions: Pulmonary TB
Phase: Phase 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: 12 Apr 2022 (actual)
Primary completion: 8 Apr 2024 (actual)
Study completion: 19 May 2024 (actual)
First posted: 3 Feb 2022 (actual)
Results: Posted 12 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Eligible participants for this study have a diagnosis of pulmonary DS-TB.

This is a Phase 2b/c multicenter, open-label, randomized, dose-finding study, consisting of up to 26 weeks of treatment period.

Following a screening period of up to 14 days, eligible participants will be randomized in the study.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 4

Arm	Type	Receives
Delamanid + Bedaquiline + OPC-167832 10 mg	Experimental	Drug: Delamanid, Drug: Bedaquiline, Drug: OPC-167832 10 mgParticipants will receive a combination regimen of delamanid, 300 mg, oral tablets, once daily (QD), bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, thrice weekly (TIW) and OPC-167832, 10 mg, oral tablets, QD for a total of 17 weeks.
Delamanid + Bedaquiline + OPC-167832 30 mg	Experimental	Drug: Delamanid, Drug: Bedaquiline, Drug: OPC-167832 30 mgParticipants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 30 mg, oral tablets, QD for a total of 17 weeks.
Delamanid + Bedaquiline + OPC-167832 90 mg	Experimental	Drug: Delamanid, Drug: Bedaquiline, Drug: OPC-167832 90 mgParticipants will receive a combination regimen of delamanid, 300 mg, oral tablets, QD, bedaquiline, 400 mg, oral tablets, QD for 2 weeks, then 200 mg, TIW and OPC-167832, 90 mg, oral tablets, QD for a total of 17 weeks.
Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)	Active comparator	Drug: RHEZ, Drug: Rifampin, Drug: IsoniazidParticipants will receive RHEZ, orally, QD for 8 weeks followed by 18 weeks of rifampin and isoniazid for a total of 26 weeks.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Able to provide written, informed consent prior to initiation of any trial-related procedures or treatments, and able, in the opinion of the investigator, to comply with all the requirements of the trial.
Male or female participants between 18 and 65 years of age (inclusive) at the screening visit.
Body weight ≥ 35.0 kg at the screening visit.
Newly diagnosed, rifampin and isoniazid susceptible (on the screening sample) pulmonary TB.
Able to spontaneously produce sputum.

Key exclusion criteria (26 listed)

Participants are known or suspected of having resistance to rifampin, isoniazid, ethambutol, pyrazinamide, DLM, or BDQ either confirmed by the laboratory, or based on epidemiological history, at screening.
Evidence of clinically significant metabolic (for example, including ongoing or current hypokalemia [ie, potassium <3.5 mEq/dL at screening]), gastrointestinal, neurological, psychiatric, endocrine or liver (eg, 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, uncontrolled 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 DLM, BDQ, OPC 167832, rifampin, isoniazid, pyrazinamide, or ethambutol is contraindicated.

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
DelamanidDelamanid (300 mg QD) for 17 weeks	Drug	Delamanid + Bedaquiline + OPC-167832 10 mg, Delamanid + Bedaquiline + OPC-167832 30 mg, Delamanid + Bedaquiline + OPC-167832 90 mg
BedaquilineBedaquiline (400 mg QD x 2 weeks, then 200 mg TIW) for 17 weeks	Drug	Delamanid + Bedaquiline + OPC-167832 10 mg, Delamanid + Bedaquiline + OPC-167832 30 mg, Delamanid + Bedaquiline + OPC-167832 90 mg
RHEZAlso: RIFAFOURRHEZ (RIFAFOUR single dose combination tablets) for 8 weeks	Drug	Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)
RifampinRifampin tablets for 18 weeks	Drug	Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)
IsoniazidIsoniazid tablets for 18 weeks	Drug	Rifampin, Isoniazid, Ethambutol, and Pyrazinamide (RHEZ)
OPC-167832 10 mgOPC-167832 (10 mg QD) for 17 weeks	Drug	Delamanid + Bedaquiline + OPC-167832 10 mg
OPC-167832 30 mgOPC-167832 (30 mg QD) for 17 weeks	Drug	Delamanid + Bedaquiline + OPC-167832 30 mg
OPC-167832 90 mgOPC-167832 (90 mg QD) for 17 weeks	Drug	Delamanid + Bedaquiline + OPC-167832 90 mg

Primary outcome

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria
Time frame: From first dose of study drug up to end of follow up period (up to Week 52)
An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment. Serious AE are AEs that leads to death, is life threatening, requires or prolongs hospitalization, significant disability, congenital anomaly or birth defect, and other medically important serious advent. AEs were graded on a severity 3-point scale as follows: Mild: Discomfort noticed, but no disruption to daily activity.; Moderate: Discomfort sufficient to reduce or affect normal daily activity.;Severe: Inability to work or perform normal daily activity. As pre-specified in statistical analysis plan (SAP),Division of AIDS (DAIDS v2.1) criteria was used and AEs graded as follows:Grade 1-Mild;Grade 2-Moderate;Grade 3-Severe;Grade 4-Life Threatening;Grade 5-Death.
Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities
Time frame: Baseline up to end of follow up period (up to Week 52)
Laboratory assessments included clinical chemistry (Albumin, Alkaline Phosphatase, Aspartate Aminotransferase, Total Bilirubin, Calcium, Creatinine, estimated Glomerular Filtration Rate (eGFR), Glucose, Fasting and Non-Fasting, Cholesterol, Inorganic Phosphorus, Magnesium, Potassium, Sodium, Triglycerides and Uric Acid), hematology (Activated Partial Thromboplastin Time, Prothrombin Time, Partial Thromboplastin Time, International Normalized Ratio (INR), Absolute CD4+ Count, Absolute Lymphocytes, Absolute Neutrophil Count, Hemoglobin, Platelet Count, White Blood Cell), and urinalysis (Urine Glucose, Blood and Protein). As pre-specified in statistical analysis plan (SAP), Division of AIDS (DAIDS) criteria was used and abnormalities were graded as follows:Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death. Laboratory values with DAIDS Grade ≥3 were considered as potentially clinically relevant abnormalities and are reported here.
Number of Participants With Potentially Clinically Relevant Abnormalities in the Vital Signs
Time frame: Baseline up to end of follow up period (up to Week 52)
Vital signs measurements included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, body weight, and body temperature. Blood pressure (i.e., SBP, DBP) and heart rate were measured in the supine and sitting positions after the participant had been in each position for at least 3 minutes. The participants were categorized based on the clinically relevant vital sign values as per DAIDS criteria pre-specified in SAP. Each vital sign parameter was graded using the DAIDS criteria as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Potentially Life Threatening; Grade 5 - Death. The categories with at least one participant with clinically significant value of any grade for vital signs are reported here.
Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities
Time frame: Baseline up to end of follow up period (up to Week 52)
3 ECGs were performed at baseline (Day -1) spaced 5 to 10 minutes apart, and 3 ECGs at all subsequent visits during the treatment and follow-up periods. The categories with at least one participant with clinically relevant ECG abnormalities are reported here.
Number of Participants With an AE Reported as DAIDS Grade 3 or Higher
Time frame: From first dose of study drug up to end of follow up period (up to approximately Week 52)
An AE was defined as any untoward medical occurrence in a clinical trial participant administered a treatment that does not necessarily have a causal relationship with the treatment. All AEs were graded on a 5-point scale according to DAIDS Table for Grading the Severity of Adult and Pediatric AEs as follows: Grade 1 - Mild; Grade 2 - Moderate; Grade 3 - Severe; Grade 4 - Life Threatening; Grade 5 - Death.
Number of Participants With TEAEs Leading to Discontinuation of Treatment
Time frame: From first dose of the study drug up to end of follow up period (up to approximately Week 52)
An AE was defined as any untoward medical occurrence in a clinical trial participant administered an investigational medicinal product or trial treatment and which does not necessarily have a causal relationship with this treatment. TEAEs are AEs with an onset date on or after the start of treatment.
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) in Mycobacteria Growth Indicator Tube® (MGIT) by End of Treatment (Week 17)
Time frame: Week 17
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% confidence interval (CI) was calculated using Clopper Pearson (exact) confidence interval model.
Percentage of Participants Who Achieved SCC in MGIT by End of Treatment (Week 26)
Time frame: Week 26
A participant was classified as having achieved SCC if the participant achieved first 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis at least 1 week apart (±4 days) after his/her last sputum culture that was positive for growth, and did not have a positive sputum culture result in between, and by the end of the treatment. Efficacy was assessed by using the MGIT liquid culture system. 95% CI is calculated using Clopper Pearson (exact) confidence interval model.

5 secondary outcomes

Percentage of Participants Who Achieved SCC in MGIT by the End of 8 Weeks of Treatment
Time frame: Week 8
Time to Detection of MGIT Cultures
Time frame: Baseline up to Week 52
Percentage of Participants Achieving Negative Sputum Lipoarabinomannan (LAM) by 8 Weeks of Treatment and by End of Treatment
Time frame: Week 8, and End of Treatment Period - Week 17 (for OPC-167832 arms) and Week 26 (for RHEZ arm)
Percentage of Participants With Acquired Drug Resistance
Time frame: Baseline up to Week 52
Time to Sputum Culture Conversion (SCC)
Time frame: From the first dose of the study up to the end of the follow-up period (up to Week 52)

Results and safety

Results posted to the registry on 12 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Delamanid + Bedaquiline + OPC-167832 10 mg	20	20
Delamanid + Bedaquiline + OPC-167832 30 mg	42	39
Delamanid + Bedaquiline + OPC-167832 90 mg	39	38
RHEZ	21	21

Primary outcome: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria

Time frame: From first dose of study drug up to end of follow up period (up to Week 52). Count of participants. Unit: Participants

Measure	Delamanid + Bedaquiline + OPC-167832 10 mg n = 20	Delamanid + Bedaquiline + OPC-167832 30 mg n = 42	Delamanid + Bedaquiline + OPC-167832 90 mg n = 38	RHEZ n = 21
TEAE	17	37	30	21
Serious TEAE	2	3	0	0
Severe TEAE	3	5	2	1
TEAE Related to Study Drug	4	8	5	6
TEAE Leading to Study Discontinuation	0	1	0	0
TEAE Leading to Death	0	1	0	0
DAIDS Grade 1 TEAE	4	12	9	8
DAIDS Grade 2 TEAE	9	19	17	12

Population analysed: Safety analysis set included all randomized participants who took any dose of the study treatment.

Primary outcome: Number of Participants With Potentially Clinically Relevant Laboratory Test Abnormalities

Time frame: Baseline up to end of follow up period (up to Week 52). Count of participants. Unit: Participants

Measure	Delamanid + Bedaquiline + OPC-167832 10 mg n = 20	Delamanid + Bedaquiline + OPC-167832 30 mg n = 42	Delamanid + Bedaquiline + OPC-167832 90 mg n = 38	RHEZ n = 21
Alanine Aminotransferase (U/L): High: Grade 3	0	0	0	1
Aspartate Aminotransferase (U/L): High: Grade 3	0	1	2	1
Aspartate Aminotransferase (U/L): High: Grade 4	1	0	1	0
Bilirubin (umol/L): High: Grade 3	0	0	1	0
Bilirubin (umol/L): High: Grade 4	1	0	0	0
Cholesterol (Total) (mmol/L): High: Grade 3	0	0	1	0
Creatinine (umol/L): High: Grade 3	3	3	5	1
eGFR (mL/min): Low: Grade 3	2	6	8	0

Population analysed: Safety Analysis Set included all randomized participants who took any dose of the study treatment. "Number analyzed" indicates the number of participants evaluable for the specific category.

Primary outcome: Number of Participants With Potentially Clinically Relevant Abnormalities in the Vital Signs

Time frame: Baseline up to end of follow up period (up to Week 52). Count of participants. Unit: Participants

Measure	Delamanid + Bedaquiline + OPC-167832 10 mg n = 20	Delamanid + Bedaquiline + OPC-167832 30 mg n = 42	Delamanid + Bedaquiline + OPC-167832 90 mg n = 38	RHEZ n = 21
Hypertension- DBP: Grade 1	8	8	13	8
Hypertension- DBP: Grade 2	2	4	3	1
Hypertension- DBP: Grade 3	1	2	1	1
Hypertension- SBP: Grade 1	8	10	16	8
Hypertension- SBP: Grade 2	3	2	2	2
Hypertension- SBP: Grade 3	1	0	1	0
Body Temperature Increased: Grade 1	1	3	2	2
Body Temperature Increased: Grade 2	0	3	3	2

Population analysed: Safety analysis set included all randomized participants who took any dose of the study treatment.

Primary outcome: Number of Participants With Potentially Clinically Relevant Electrocardiogram (ECG) Abnormalities

Time frame: Baseline up to end of follow up period (up to Week 52). Count of participants. Unit: Participants

Measure	Delamanid + Bedaquiline + OPC-167832 10 mg n = 20	Delamanid + Bedaquiline + OPC-167832 30 mg n = 42	Delamanid + Bedaquiline + OPC-167832 90 mg n = 38	RHEZ n = 21
First Degree AV Block: > 200 msec	1	6	3	0
Increase in QT: >450 msec	4	7	3	2
Increase in QT: >480 msec	2	0	0	0
Increase in QTcB: >450 msec	5	15	7	3
Increase in QTcB: >480 msec	2	4	0	0
Increase in QTcB: >60 Increase from baseline	0	2	1	0
Increase in QTcB: >=30 to <=60 Increase from baseline	6	20	13	5
Increase in QTcF: >450 msec	5	8	4	1

Population analysed: Safety analysis set included all randomized participants who took any dose of the study treatment.

5 secondary outcomes are reported in the full results.

Adverse events

Time frame: From first dose of the study drug up to end of follow up period (up to Week 52). Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Delamanid + Bedaquiline + OPC-167832 10 mg	2 of 20 (10%)	17 of 20 (85%)	0 of 20
Delamanid + Bedaquiline + OPC-167832 30 mg	3 of 42 (7.1%)	31 of 42 (73.8%)	1 of 42
Delamanid + Bedaquiline + OPC-167832 90 mg	0 of 38 (0%)	25 of 38 (65.8%)	0 of 38
RHEZ	0 of 21 (0%)	20 of 21 (95.2%)	0 of 21

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42214407Dawson R, Diacon AH, Variava E, Moloantoa T, Brumskine W, Ngwanto T, Zuma-Gwala N, Osman A, Rassool M, Bennet JA, Liu Y, Xu R, Li W, Takuva S, Hafkin J. Efficacy and safety of a 4-month quabodepistat, delamanid, and bedaquiline regimen for drug-susceptible pulmonary tuberculosis: a multicentre, open-label, randomised, proof-of-concept, non-inferiority, phase 2b/c trial. Lancet Infect Dis. 2026 May 29:S1473-3099(26)00143-X. doi: 10.1016/S1473-3099(26)00143-X. Online ahead of print.
Derived from this study: PubMed 38243296Dawson R, Diacon AH, Takuva S, Liu Y, Zheng B, Karwe V, Hafkin J. Quabodepistat in combination with delamanid and bedaquiline in participants with drug-susceptible pulmonary tuberculosis: protocol for a multicenter, phase 2b/c, open-label, randomized, dose-finding trial to evaluate safety and efficacy. Trials. 2024 Jan 19;25(1):70. doi: 10.1186/s13063-024-07912-5.
Otsuka Clinical Trial Website:Link provided by the sponsor.
Otsuka Clinical Trial Transparency:Link provided by the sponsor.
Individual participant dataSharing planned: Yes. Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.

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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.

The record lists no contact. Use the official record to reach the sponsor.

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Delamanid, Bedaquiline and RHEZ in people with Pulmonary TB, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 6 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 7 inclusion and 26 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 12 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 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 phase mean?

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 12 Aug 2026). 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?

Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Severe TEAEs, TEAEs Related to Study Drug, TEAEs Leading to Study Discontinuation, TEAEs Leading to Death, and All Grade TEAEs Based on DAIDS Criteria (time frame: From first dose of study drug up to end of follow up period (up to Week 52)). The study lists 8 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 NCT05221502, 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 12 Aug 2026.