Conditions: Pulmonary Tuberculosis
Keywords: Tuberculosis EBA TMC207 pretomanid Early Bactericidal Activity Pulmonary Tuberculosis PA-824 bedaquiline pyrazinamide moxifloxacin ethambutol rifafour
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 85
Healthy volunteers: no

Brief summary:
The trial will evaluate the extended bactericidal activity of 14 consecutive days of oral administration of TMC207 alone, TMC207 with pyrazinamide, TMC207 with PA-824, PA-824 with pyrazinamide and PA-824 with moxifloxacin and pyrazinamide, as determined by the rate of change of log CFU in sputum over the time period Day 0-14 in participants with smear positive pulmonary tuberculosis (TB). A control group will receive standard treatment.

Detailed description:

Arms:
arm 1: TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo administered once daily arm 2: TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: \< or = 55kg received 2 tablets/day; \>55kg to 75kg received 3 tablets/day; \>75kg received 4 tablets/day arm 3: PA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: \< or = 55kg received 2 tablets/day; \>55kg to 75kg received 3 tablets/day; \>75kg received 4 tablets/day and moxifloxacin placebo (matched to moxifloxacin tablets) administered once daily arm 4: PA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: \< or = 55kg received 2 tablets/day; \>55kg to 75kg received 3 tablets/day; \>75kg received 4 tablets/day and moxifloxacin administered once daily as 400mg tablets arm 5: Rifafour e-275 administered once daily with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dose by weight as follows: 30kg-37kg received 2 tablets/day; 38kg-54kg received 3 tablets/days; 55kg-70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day arm 6: TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus PA-824 administered once daily as 200mg tablets

Interventions: intervention 1: PA-824 intervention 2: Pyrazinamide intervention 3: TMC207 intervention 4: Rifafour intervention 5: Moxifloxacin
Intervention descriptions: intervention 1: 200 mg tablet, once daily for 14 days intervention 2: Dosed by Weight intervention 3: TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 intervention 4: Rifafour e-275 intervention 5: moxifloxacin 400 mg

Protocol document: