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

A Phase 2, Open-label, Randomized Controlled Trial to Assess the Safety, Bactericidal Activity, and Pharmacokinetics of Nicotinamide in Combination With Bedaquiline, Pretomanid, and Linezolid in Adults With Drug-susceptible Pulmonary Tuberculosis

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.

Study Overview

• Status: Recruiting
• Conditions: Drug Susceptible Pulmonary Tuberculosis
• Intervention / Treatment: Drug: Bedaquiline, pretomanid, linezolid; Drug: Bedaquiline, pretomanid, linezolid; Drug: Bedaquiline, pretomanid, linezolid; Dietary supplement: Nicotinamide (NAM)

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Gates MRI; Phone Number: +857-702-2108; Email: Clinical.trials@gatesmri.org
• Study Contact Backup: Name: Gates MRI; Phone Number: +1-866-789-5757; Email: Clinical.trials@gatesmri.org

Study Locations

• South Africa
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 2001
      • Recruiting
      • Wits RHI - Shandukani Research
      • Contact: Nkosiphile Ndlovu, MD; Phone Number: 011 358 5300; Email: nkndlovu@wrhi.ac.za
      • Contact: Zikhona Njengele Tetyana; Phone Number: 083 3642; Email: znjengele-tetyana@wrhi.ac.za
      • Principal Investigator: Nkosiphile Ndlovu, MD
    • Pretoria, Gauteng, South Africa, 87
      • Recruiting
      • The Aurum Institute Clinical Research Site - Pretoria
      • Contact: Vaneshree Govender, MD; Phone Number: 012 844 0145; Email: vgovender@auruminstitute.org
      • Contact: Innocent Shibambo; Phone Number: 082 495 9556; Email: ishibambo@auruminstitute.org
      • Principal Investigator: Vaneshree Govender, MD
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7530
      • Recruiting
      • TASK Clinical Research Centre
      • Contact: Andrew Parker, MD; Phone Number: 021 9171044; Email: dr.andrew@task.org.za
      • Contact: Lukhanyile Ketelo; Phone Number: 021 9171044; Email: l.ketelo@taskclinical.com
      • Principal Investigator: Andrew Parker, MD
    • Cape Town, Western Cape, South Africa, 7700
      • Not yet recruiting
      • Centre of Tuberculosis Research Innovation
      • Principal Investigator: Rodney Dawson, MD
      • Contact: Rodney Dawson, MD; Phone Number: 021 406 6850; Email: rodney.dawson@uct.ac.za
      • Contact: Shanel Linde; Email: shanel.linde@uct.ac.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BPAL/NAM1500; Nicotinamide, bedaquiline, pretomanid, linezolid	Drug: Bedaquiline, pretomanid, linezolid; 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; Drug: Bedaquiline, pretomanid, linezolid; Group 2 (Approximately 55 participants): Combination of NAM 2500 mg BID with bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days; Drug: Bedaquiline, pretomanid, linezolid; Group 3 (active control; approximately 55 participants): Combination of bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days; Dietary supplement: Nicotinamide (NAM); 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; Other Names: Nicotinamide also abbreviated as NAM and also known as niacinamide .
Experimental: BPAL/NAM2500; Nicotinamide, bedaquiline, pretomanid, linezolid	Drug: Bedaquiline, pretomanid, linezolid; 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; Drug: Bedaquiline, pretomanid, linezolid; Group 2 (Approximately 55 participants): Combination of NAM 2500 mg BID with bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days; Drug: Bedaquiline, pretomanid, linezolid; Group 3 (active control; approximately 55 participants): Combination of bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days; Dietary supplement: Nicotinamide (NAM); 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; Other Names: Nicotinamide also abbreviated as NAM and also known as niacinamide .
Active Comparator: BPAL; Bedaquiline, pretomanid, linezolid	Drug: Bedaquiline, pretomanid, linezolid; 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; Drug: Bedaquiline, pretomanid, linezolid; Group 2 (Approximately 55 participants): Combination of NAM 2500 mg BID with bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days; Drug: Bedaquiline, pretomanid, linezolid; Group 3 (active control; approximately 55 participants): Combination of bedaquiline (200 mg QD), pretomanid (200 mg QD), and linezolid (600 mg QD), 56 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bactericidal Activity	Time to Sputum culture conversion to negative of Mtb in MGIT sputum culture.	Randomization through Day 64 (EOT)
Bactericidal activity	Proportion of participants with Mtb-negative MGIT sputum culture(s) at Week 4 (Day 29) and Week 8 (Day 56, EOTx), where confirmation of negative sputum culture at subsequent study timepoint is not required.	Randomization through Day 56 (EOTx)
Evaluate the PK of NAM when administered with BPaL in Group 1 and 2	Concentrations of NAM and its primary metabolite by measuring specific PK parameters at Day 1 and Day 14 (see protocol).	Day 1 and Day 14

Collaborators and Investigators

• Sponsor: Gates Medical Research Institute
• Collaborators: IQVIA RDS Inc.
• Investigators: Study Director: Gates MRI, Gates Medical Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): April 17, 2026
• Primary Completion (Estimated): June 14, 2027
• Study Completion (Estimated): June 14, 2027

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 1, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: pretomanid; linezolid; Nicotinamide; bedaquiline; drug-susceptible pulmonary tuberculosis
• Additional Relevant MeSH Terms: Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Azoles; Acids, Acyclic; Carboxylic Acids; Amides; Acetamides; Acetates; Oxazolidinones; Oxazoles; Acids, Heterocyclic; Nicotinic Acids; Linezolid; Niacinamide; bedaquiline; pretomanid
• Other Study ID Numbers: Gates MRI TBD15-201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within 12 months of study completion date
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No