Drug Susceptible Pulmonary Tuberculosis
Conditions
Keywords
Nicotinamide, bedaquiline, pretomanid, linezolid, drug-susceptible pulmonary tuberculosis
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.
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
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
Sponsors
Gates Medical Research Institute
IQVIA RDS Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bactericidal Activity | From randomization through Day 64 (EOT) | 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) |
| Safety: SAEs | From randomization through Day 64 (EOT) | Proportion of participants with this event |
| Safety: TEAEs | From randomization through Day 64 (EOT) | Proportion of participants with this event |
| Safety: AESIs | From randomization through Day 64 (EOT) | Proportion of participants with this event |
| Safety: TEAEs leading to treatment discontinuation | From randomization through Day 64 (EOT) | Proportion of participants with this event |
| Safety: TEAEs leading to NAM dose reduction | From randomization through Day 64 (EOT) | Proportion of participants with this event |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bactericidal Activity | Randomization through Day 64 (EOT) | Time to Sputum culture conversion to negative of Mtb in MGIT sputum culture. |
| Bactericidal activity | Randomization through Day 56 (EOTx) | 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. |
| Evaluate the PK of NAM when administered with BPaL in Group 1 and 2 | Day 1 and Day 14 | Concentrations of NAM and its primary metabolite by measuring specific PK parameters at Day 1 and Day 14 (see protocol). |
Countries
South Africa
Contacts
CONTACTGates MRI
STUDY_DIRECTORGates MRI
Gates Medical Research Institute
Outcome results
None listed