To evaluate the efficacy, safety and tolerability at 8 weeks (2-months), 52 weeks (12-months), and 104 Weeks (24-months) post the start of the following treatment regimens in participants with: Drug Sensitive TB (DS-TB) patients given BPaMZ for 17 Weeks ( or 4 months) vs. Standard HRZE/HR treatment given for 26 weeks (or 6 months) and Drug Resistant TB (DR-TB) patients given BPaMZ for 26 Weeks (or 6 months)

Phase 2c multi-center, open-label, partially randomized clinical trial in DS-TB and DR-TB participants.

All participants in the below arms will have follow-up for a period of 104 weeks (24 months) from the start of therapy.

Participants with Drug Sensitive TB (DS-TB):

Participants with DS-TB will be randomized to one of two treatment arms. These participants will receive either BPaMZ daily for 17 weeks (4 months), or HRZE/HR combination tablets daily for 26 weeks (6 months). participants will be stratified for co-infection with human immunodeficiency virus (HIV) and cavitation.

Participants with Drug Resistant TB (DR-TB):

Participants with DR-TB will be assigned to receive BPaMZ daily for 26 weeks (6 months).

Inclusion Criteria:

• Sputum positive for tubercule bacilli (at least 1+ on the International Union Against Tuberculosis and Lung Disease [IUATLD]/WHO scale (Appendix 1) on smear microscopy) at the trial laboratory.
• Participants with one of the following pulmonary TB conditions:

DS-TB treatment arm participants should be:

• sensitive to rifampicin and isoniazid by rapid sputum based test AND
• either newly diagnosed for TB or have a history of being untreated for at least 3 years after cure from a previous episode of TB.

DR-TB treatment arm participants should be Resistant to rifampicin and/or isoniazid.

• Of non-childbearing potential or willing to practice effective methods of birth control
• Body weight (in light clothing and no shoes) ≥ 30 kg.
• Completed informed consent form

Exclusion Criteria:

• Karnofsky score <60%
• Any risk factor for QT prolongation
• Any planned contraindicated medicines
• Resistant to fluoroquinolones (rapid, sputum-based molecular screening tests).

Any of the following lab toxicities/abnormalities:

• CD4+ count < 100 cells/µL (HIV infected participants)
• platelets <75,000/mm³
• creatinine >1.5 times upper limit of normal (ULN)
• eGFR ≤ 60 mL/min
• haemoglobin <8.0 g/dL
• serum potassium less than the lower limit of normal for the laboratory.
• GGT: greater than 3 x ULN
• AST: ≥3.0 x ULN to be excluded;
• ALT: ≥3.0 x ULN to be excluded
• ALP: ≥3.0 x ULN to be excluded
• Total bilirubin: >1.5 x ULN to be excluded;
• Direct bilirubin: greater than 1x ULN to be excluded

IPD from the trial will be submitted to Critical Path Institute which will make fully anonymized data available through the Tuberculosis Platform for Aggregation of Clinical TB Studies (TB-PACTS) database. Data sets for Drug susceptibility data, Demographic data, MTB diagnostic testing results, Concomitant medications information, Adverse event information, Treatment adherence information, Co-morbidities, Treatment outcomes, HIV co-infection information, CD4 counts, TB disease symptoms from all collected IPD will be made available.

Data is expected to become available in mid-2024.

Researchers must agree to the Terms and Conditions for Use of the TB-PACTS data platform and submit an online application form to request access to the data platform.