Trial Outcomes & Findings for Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) (NC-001) (NCT NCT01215851)
NCT ID: NCT01215851
Last Updated: 2017-02-28
Results Overview
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
85 participants
Primary outcome timeframe
14 consecutive days of treatment
Results posted on
2017-02-28
Participant Flow
Patients were recruited from outpatient clinics and were admitted to the hospital for the duration of the study at one of 2 centers in Capetown, South Africa. The study was conducted between October 2010 and August 2011. Patients aged 18 and 65 years with newly diagnosed smear-positive pulmonary TB were recruited and randomized centrally.
In the screening period, TB treatment was not provided while baseline sputum was collected/tested. This period was up to 9 days, up to 6 days screening followed by 3 days baseline sputum collection. Hospitalization during this time was left to investigator discretion. 173 patients were screened and 88 patients discontinued before randomization.
Participant milestones
| Measure |
TMC207
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Treatment Period
STARTED
|
15
|
15
|
15
|
15
|
10
|
15
|
|
Treatment Period
COMPLETED
|
14
|
14
|
14
|
12
|
10
|
14
|
|
Treatment Period
NOT COMPLETED
|
1
|
1
|
1
|
3
|
0
|
1
|
|
Follow up Period
STARTED
|
14
|
14
|
14
|
12
|
10
|
14
|
|
Follow up Period
COMPLETED
|
14
|
14
|
14
|
12
|
10
|
13
|
|
Follow up Period
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
1
|
Reasons for withdrawal
| Measure |
TMC207
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Treatment Period
Adverse Event
|
1
|
1
|
1
|
3
|
0
|
1
|
|
Follow up Period
Lost to Follow-up
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) (NC-001)
Baseline characteristics by cohort
| Measure |
TMC207
n=15 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=15 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=15 Participants
PA-824 administered once daily as 200mg tablets and pyrazinamide administered once daily in 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
Total
n=85 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
15 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
15 Participants
n=4 Participants
|
10 Participants
n=21 Participants
|
15 Participants
n=10 Participants
|
85 Participants
n=115 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=21 Participants
|
0 Participants
n=10 Participants
|
0 Participants
n=115 Participants
|
|
Age, Continuous
|
31.3 years
STANDARD_DEVIATION 11.60 • n=5 Participants
|
29.1 years
STANDARD_DEVIATION 8.67 • n=7 Participants
|
29.7 years
STANDARD_DEVIATION 8.93 • n=5 Participants
|
28.3 years
STANDARD_DEVIATION 9.34 • n=4 Participants
|
27.0 years
STANDARD_DEVIATION 6.63 • n=21 Participants
|
33.3 years
STANDARD_DEVIATION 8.47 • n=10 Participants
|
30.0 years
STANDARD_DEVIATION 9.13 • n=115 Participants
|
|
Gender
Female
|
4 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
4 Participants
n=10 Participants
|
22 Participants
n=115 Participants
|
|
Gender
Male
|
11 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
12 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
11 Participants
n=10 Participants
|
63 Participants
n=115 Participants
|
|
Region of Enrollment
South Africa
|
15 participants
n=5 Participants
|
15 participants
n=7 Participants
|
15 participants
n=5 Participants
|
15 participants
n=4 Participants
|
10 participants
n=21 Participants
|
15 participants
n=10 Participants
|
85 participants
n=115 Participants
|
PRIMARY outcome
Timeframe: 14 consecutive days of treatmentPopulation: In the case of patient dropout, their patient data were included in the analyses as long as enough points were recorded to allow curve fitting. The number of patients analyzed for this outcome was 80.
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Outcome measures
| Measure |
TMC207
n=14 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=14 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=13 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=14 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-14).
|
0.061 log10CFU/ml/day
Standard Deviation 0.068
|
0.131 log10CFU/ml/day
Standard Deviation 0.102
|
0.154 log10CFU/ml/day
Standard Deviation 0.040
|
0.233 log10CFU/ml/day
Standard Deviation 0.128
|
0.140 log10CFU/ml/day
Standard Deviation 0.094
|
0.114 log10CFU/ml/day
Standard Deviation 0.050
|
SECONDARY outcome
Timeframe: Day 0-2Population: In the case of patient dropout, their patient data were included in the analyses as long as enough points were recorded to allow curve fitting. The number patients analyzed for this measure was 84.
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Outcome measures
| Measure |
TMC207
n=15 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=15 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=15 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=14 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 0-2).
|
-0.022 log10CFU/ml/day
Standard Deviation 0.121
|
0.079 log10CFU/ml/day
Standard Deviation 0.167
|
0.170 log10CFU/ml/day
Standard Deviation 0.082
|
0.315 log10CFU/ml/day
Standard Deviation 0.133
|
0.177 log10CFU/ml/day
Standard Deviation 0.188
|
0.114 log10CFU/ml/day
Standard Deviation 0.149
|
SECONDARY outcome
Timeframe: Day 2-14Population: In the case of patient dropout, their patient data were included in the analyses as long as enough points were recorded to allow curve fitting. The number of patients analyzed for this measure was 80.
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Outcome measures
| Measure |
TMC207
n=14 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=14 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=13 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=14 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 2-14).
|
0.076 log10CFU/ml/day
Standard Deviation 0.069
|
0.143 log10CFU/ml/day
Standard Deviation 0.109
|
0.148 log10CFU/ml/day
Standard Deviation 0.043
|
0.222 log10CFU/ml/day
Standard Deviation 0.130
|
0.135 log10CFU/ml/day
Standard Deviation 0.103
|
0.114 log10CFU/ml/day
Standard Deviation 0.047
|
SECONDARY outcome
Timeframe: Day 7-14Population: In the case of patient dropout, their patient data were included in the analyses as long as enough points were recorded to allow curve fitting. The number of patients analyzed for this outcome was 80.
Log10 CFU rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (log10CFU versus Day). Mean log10 CFU changes from baseline were compared. A higher slope value indicates a greater change in log10 CFU from baseline. Note that to facilitate interpretation the sign of these slopes are reversed for logCFU. A positive slope value therefore indicates a reduction in log10 CFU from baseline.
Outcome measures
| Measure |
TMC207
n=14 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=14 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=13 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=14 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Early Bactericidal Activity (EBA) Measured as the Mean Rate of Change of log10 Colony Forming Units (CFU) of M. Tuberculosis Per ml Sputum on Solid Medium Over Time (Days 7-14).
|
0.123 log10CFU/ml/day
Standard Deviation 0.097
|
0.152 log10CFU/ml/day
Standard Deviation 0.120
|
0.124 log10CFU/ml/day
Standard Deviation 0.080
|
0.175 log10CFU/ml/day
Standard Deviation 0.146
|
0.136 log10CFU/ml/day
Standard Deviation 0.102
|
0.114 log10CFU/ml/day
Standard Deviation 0.069
|
SECONDARY outcome
Timeframe: 14 DaysPopulation: In the case of patient dropout, their patient data were included in the analyses as long as enough points were recorded to allow curve fitting. The number of patients analyzed for this measure was 81.
The TTP was measured in the Mycobacterial Growth Indicator Tube (MGIT) (Bactec MGIT960) automated liquid culture system from overnight sputum. TTP rates of change were calculated for each individual patient from the slopes β1 and β2 of the bi-linear regression fitted to the data for each individual patient (TTP versus Day).
Outcome measures
| Measure |
TMC207
n=14 Participants
TMC207 administered once daily as 100mg tablets for a total daily dose of 700mg on Day 1; 500mg on Day 2; 400mg on Days 3-14 plus pyrazinamide placebo tablets (matched to pyrazinamide tablets) administered once daily on Days 1-14 dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
TMC207 and Pyrazinamide
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day
|
PA-824 and Pyrazinamide
n=14 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin placebo tablets (matched to moxifloxacin tablets) administered once daily on Days 1-14
|
PA-824 and Moxifloxacin and Pyrazinamide
n=13 Participants
PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14, pyrazinamide administered once daily on Days 1-14 as 500mg tablets dosed by weight as follows: \< or = 55kg 2 tablets/day; \>55kg to 75kg 3 tablets/day; \>75kg 4 tablets/day, and moxifloxacin administered once daily as 400mg tablets for a total daily dose of 400mg on Days 1-14
|
Rifafour e-275 mg
n=10 Participants
Rifafour e-275 administered once daily on Days 1-14 with each tablet containing 150mg rifampicin, 75mg isoniazid, 400mg pyrazinamide, and 275mg ethambutol and dosed by weight as follows: 30kg - 37kg received 2 tablets/day; 38kg - 54kg received 3 tablets/day; 55kg - 70kg received 4 tablets/day; \> or = 71kg received 5 tablets/day
|
TMC207 and PA-824
n=15 Participants
TMC207 administered once daily as 100mg tablet for total daily dose of 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 administered once daily as 200mg tablets for a total daily dose of 200mg on Days 1-14
|
|---|---|---|---|---|---|---|
|
Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)
|
5.414 time (h) to positive per day
Standard Deviation 3.523
|
9.970 time (h) to positive per day
Standard Deviation 6.987
|
8.805 time (h) to positive per day
Standard Deviation 3.468
|
18.482 time (h) to positive per day
Standard Deviation 22.582
|
11.841 time (h) to positive per day
Standard Deviation 3.932
|
5.855 time (h) to positive per day
Standard Deviation 2.785
|
Adverse Events
TMC207
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
TMC207 and Pyrazinamide
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
PA-824 and Pyrazinamide
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
PA-824 and Moxifloxacin and Pyrazinamide
Serious events: 1 serious events
Other events: 8 other events
Deaths: 0 deaths
Rifafour e-275 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
TMC207 and PA-824
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TMC207
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide placebo
|
TMC207 and Pyrazinamide
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide (dosed by weight)
|
PA-824 and Pyrazinamide
n=15 participants at risk
PA-824 200mg and pyrazinamide (dosed by weight)and moxifloxacin placebo
|
PA-824 and Moxifloxacin and Pyrazinamide
n=15 participants at risk
PA-824 200 mg and pyrazinamide (dosed by weight) and moxifloxacin 400 mg
|
Rifafour e-275 mg
n=10 participants at risk
Rifafour e-275 275 mg
|
TMC207 and PA-824
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 200 mg
|
|---|---|---|---|---|---|---|
|
Infections and infestations
Worsening of Pulmonary Tuberculosis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
|
Infections and infestations
Neurocysticercosis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
Other adverse events
| Measure |
TMC207
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide placebo
|
TMC207 and Pyrazinamide
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide (dosed by weight)
|
PA-824 and Pyrazinamide
n=15 participants at risk
PA-824 200mg and pyrazinamide (dosed by weight)and moxifloxacin placebo
|
PA-824 and Moxifloxacin and Pyrazinamide
n=15 participants at risk
PA-824 200 mg and pyrazinamide (dosed by weight) and moxifloxacin 400 mg
|
Rifafour e-275 mg
n=10 participants at risk
Rifafour e-275 275 mg
|
TMC207 and PA-824
n=15 participants at risk
TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 200 mg
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
20.0%
3/15 • Number of events 3
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
20.0%
2/10 • Number of events 2
|
6.7%
1/15 • Number of events 1
|
|
Gastrointestinal disorders
Nausea
|
13.3%
2/15 • Number of events 2
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Nervous system disorders
Headache
|
13.3%
2/15 • Number of events 3
|
13.3%
2/15 • Number of events 2
|
13.3%
2/15 • Number of events 2
|
13.3%
2/15 • Number of events 3
|
10.0%
1/10 • Number of events 1
|
20.0%
3/15 • Number of events 3
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal pain lower
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Gastrointestinal disorders
Abdominal pain upper
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Investigations
Alanine aminotransferase increased
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
13.3%
2/15 • Number of events 2
|
0.00%
0/10
|
13.3%
2/15 • Number of events 2
|
|
Investigations
Gamma-glutamyltransferase increased
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Investigations
Blood alkaline phosphatase increased
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Investigations
Blood amylase increased
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Investigations
electrocardiogram QT prolonged
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
|
Infections and infestations
Furuncle
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
|
Infections and infestations
Nasopharyngitis
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Infections and infestations
Tooth abscess
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Infections and infestations
Vulvovaginal candidiasis
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
10.0%
1/10 • Number of events 1
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
6.7%
1/15 • Number of events 1
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
13.3%
2/15 • Number of events 2
|
|
Eye disorders
Conjunctival hemorrhage
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Eye disorders
Eyelid edema
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
|
Eye disorders
Lenticular opacities
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
|
General disorders
Hyperthermia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
|
Injury, poisoning and procedural complications
Skin laceration
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/10
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Type I diabetes mellitus
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
6.7%
1/15 • Number of events 1
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/10
|
0.00%
0/15
|
Additional Information
Daniel E. Everitt, MD, Vice President and Senior Medical Officer
Global Alliance for TB Drug Development
Phone: (212) 227-7540
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee All unpublished information given to the Investigator by the Sponsor shall not be published/disclosed to a third party, other than to IEC/IRB, within the understanding of the confidentiality, without the prior written consent of the Sponsor. Results of this research will be submitted for publication as soon as feasible upon completion of the study in the form of a joint publication(s) between the Sponsor and Investigator(s), including site clinical and laboratory investigators, as appropriate.
- Publication restrictions are in place
Restriction type: OTHER