Bactericidal Activity and Safety of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Drug-susceptible Pulmonary Tuberculosis

NCT07517445 | Recruiting Phase 2 DMC

• 1 other identifier: Gates MRI TBD15-201
• Study Type: interventional
• Target: 165
• Locations: 1 country
• Sites: 4

Brief Summary

The purpose of this study is to determine if nicotinamide in combination with bedaquiline, pretomanid, and linezolid, is safe and effective in treating drug-susceptible pulmonary tuberculosis.

Conditions

Drug Susceptible Pulmonary Tuberculosis

Keywords

Nicotinamide; bedaquiline; pretomanid; linezolid; drug-susceptible pulmonary tuberculosis

Outcome Measures

Primary Outcomes (6)

• Bactericidal Activity

  Proportion of participants with sputum culture conversion SCC to negative for Mtb in MGIT liquid culture by Week 8 (Day 56, End of Treatment \[EOTx\]), defined as two consecutive Mtb-negative culture results, collected at least 1 day apart (i.e., not collected on the same day), occurring by Week 9 (Day 64) with no subsequent Mtb-positive cultures through Week 9 (Day 64)

  From randomization through Day 64 (EOT)

• Safety: SAEs

  Proportion of participants with this event

  From randomization through Day 64 (EOT)

• Safety: TEAEs

  Proportion of participants with this event

  From randomization through Day 64 (EOT)

• Safety: AESIs

  Proportion of participants with this event

  From randomization through Day 64 (EOT)

• Safety: TEAEs leading to treatment discontinuation

  Proportion of participants with this event

  From randomization through Day 64 (EOT)

• Safety: TEAEs leading to NAM dose reduction

  Proportion of participants with this event

  From randomization through Day 64 (EOT)

Secondary Outcomes (3)

• Bactericidal Activity

  Randomization through Day 64 (EOT)

• Bactericidal activity

  Randomization through Day 56 (EOTx)

• Evaluate the PK of NAM when administered with BPaL in Group 1 and 2

  Day 1 and Day 14

Study Arms (3)

BPAL/NAM1500

EXPERIMENTAL

Nicotinamide, bedaquiline, pretomanid, linezolid

Drug: Bedaquiline, pretomanid, linezolid; Dietary Supplement: Nicotinamide (NAM)

BPAL/NAM2500

EXPERIMENTAL

Nicotinamide, bedaquiline, pretomanid, linezolid

Drug: Bedaquiline, pretomanid, linezolid; Dietary Supplement: Nicotinamide (NAM)

BPAL

ACTIVE COMPARATOR

Bedaquiline, pretomanid, linezolid

Drug: Bedaquiline, pretomanid, linezolid

Interventions

Bedaquiline, pretomanid, linezolid DRUG

Group 1 (Approximately 55 participants), Combination of NAM 1500 mg twice daily (BID) with bedaquiline (200 mg once daily \[QD\]), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days

BPAL/NAM1500

Nicotinamide (NAM) DIETARY_SUPPLEMENT

Group 1 (Approximately 55 participants), Combination of NAM 2500 mg twice daily (BID) with bedaquiline (200 mg once daily \[QD\]), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days

Also known as: Nicotinamide also abbreviated as NAM and also known as niacinamide .

BPAL/NAM1500; BPAL/NAM2500

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-65 years at consent
• Body weight 40-100 kg at screening
• Written informed consent obtained
• Newly diagnosed pulmonary TB, rifampicin- and isoniazid-sensitive
• ≥1+ AFB smear OR positive Xpert semi-quantitative result
• Molecular confirmation of M. tuberculosis
• Chest X-ray consistent with TB (Investigator assessment)
• Able to spontaneously produce sputum
• Contraception requirements met
• Females Of Child Bearing Potential: 2 approved contraceptive methods or abstinence
• Males: contraception or abstinence through 90 days post-dose

You may not qualify if:

• Prior TB within 3 years, \>1 prior episode, or anti-TB treatment within 60 days
• Extrapulmonary TB (except non-significant pleural/lymph node disease)
• Clinically significant comorbidities or substance abuse impacting safety/compliance
• Pregnant or breastfeeding
• HIV-positive AND any of the following:
• Not on ART or on ART \<3 months
• CD4 \<200 cells/µL
• Viral load \>200 copies/mL
• AIDS-defining illness (other than pulmonary TB)
• Screening lab abnormalities (protocol-defined LFTs, hematology, hepatitis B or C, HbA1c)
• Clinically significant ECG abnormality
• Use of prohibited concomitant medications (e.g., strong CYP3A4 modifiers, certain SSRIs)

Sponsors & Collaborators

• IQVIA RDS Inc.: collaborator
• Gates Medical Research Institute: lead

Study Sites (4)

Wits RHI - Shandukani Research

Johannesburg, Gauteng, 2001, South Africa

RECRUITING

The Aurum Institute Clinical Research Site - Pretoria

Pretoria, Gauteng, 87, South Africa

RECRUITING

TASK Clinical Research Centre

Cape Town, Western Cape, 7530, South Africa

RECRUITING

Centre of Tuberculosis Research Innovation

Cape Town, Western Cape, 7700, South Africa

NOT YET RECRUITING

MeSH Terms

Interventions

bedaquiline; pretomanid; Linezolid; Niacinamide

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nicotinic Acids; Acids, Heterocyclic; Pyridines

Study Officials

• Gates MRI

  Gates Medical Research Institute

  STUDY DIRECTOR

Central Study Contacts

Gates MRI

CONTACT

+857-702-2108; Clinical.trials@gatesmri.org

Gates MRI

CONTACT

+1-866-789-5757; Clinical.trials@gatesmri.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2026
• First Posted: April 8, 2026
• Study Start: April 17, 2026
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): June 14, 2027
• Last Updated: May 22, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Within 12 months of study completion date
• Access Criteria: Anonymized participant-level data may be shared with the external research in accordance with trial participant' written and executed informed consent and applicable local regulations. Qualified research may submit a request along with a research proposal to Gates MRI for review. A data sharing agreement must be in place before any clinical trial data are shared. Additional restrictions may apply due to contractual obligations or regulatory constraints.

Locations

ZA (4)