RecruitingPhase 2NCT07517445

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


Sponsor

Gates Medical Research Institute

Enrollment

165 participants

Start Date

Apr 13, 2026

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 65 Years

Inclusion Criteria11

  • 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 Criteria12

  • 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)

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Interventions

DRUGBedaquiline, 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

DRUGBedaquiline, 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

DRUGBedaquiline, 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_SUPPLEMENTNicotinamide (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


Locations(4)

Wits RHI - Shandukani Research

Johannesburg, Gauteng, South Africa

The Aurum Institute Clinical Research Site - Pretoria

Pretoria, Gauteng, South Africa

TASK Clinical Research Centre

Cape Town, Western Cape, South Africa

Centre of Tuberculosis Research Innovation

Cape Town, Western Cape, South Africa

View Full Details on ClinicalTrials.gov

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NCT07517445


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