Trial Outcomes & Findings for Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) (NCT NCT01691534)
NCT ID: NCT01691534
Last Updated: 2016-12-13
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
105 participants
Primary outcome timeframe
14 consecutive days of treatment
Results posted on
2016-12-13
Participant Flow
Participant milestones
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
15
|
15
|
15
|
15
|
15
|
|
Overall Study
COMPLETED
|
15
|
14
|
14
|
14
|
15
|
14
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
1
|
0
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z)
Baseline characteristics by cohort
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=15 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
Total
n=105 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|---|---|
|
Race/Ethnicity, Customized
Black
|
9 participants
n=5 Participants
|
5 participants
n=7 Participants
|
6 participants
n=5 Participants
|
8 participants
n=4 Participants
|
8 participants
n=21 Participants
|
6 participants
n=8 Participants
|
9 participants
n=8 Participants
|
51 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Asian
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
0 participants
n=8 Participants
|
0 participants
n=8 Participants
|
1 participants
n=24 Participants
|
|
Sex: Female, Male
Female
|
3 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
6 Participants
n=21 Participants
|
6 Participants
n=8 Participants
|
8 Participants
n=8 Participants
|
40 Participants
n=24 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=5 Participants
|
12 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
9 Participants
n=21 Participants
|
9 Participants
n=8 Participants
|
7 Participants
n=8 Participants
|
65 Participants
n=24 Participants
|
|
Age, Continuous
|
35.5 years
STANDARD_DEVIATION 8.74 • n=5 Participants
|
33.4 years
STANDARD_DEVIATION 14.22 • n=7 Participants
|
33.3 years
STANDARD_DEVIATION 11.15 • n=5 Participants
|
30.9 years
STANDARD_DEVIATION 13.12 • n=4 Participants
|
32.4 years
STANDARD_DEVIATION 11.44 • n=21 Participants
|
28.4 years
STANDARD_DEVIATION 8.77 • n=8 Participants
|
34.3 years
STANDARD_DEVIATION 10.25 • n=8 Participants
|
32.6 years
STANDARD_DEVIATION 11.15 • n=24 Participants
|
|
Race/Ethnicity, Customized
White
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
0 participants
n=21 Participants
|
0 participants
n=8 Participants
|
0 participants
n=8 Participants
|
1 participants
n=24 Participants
|
|
Race/Ethnicity, Customized
Mixed Ethnic
|
6 participants
n=5 Participants
|
9 participants
n=7 Participants
|
9 participants
n=5 Participants
|
7 participants
n=4 Participants
|
6 participants
n=21 Participants
|
9 participants
n=8 Participants
|
6 participants
n=8 Participants
|
52 participants
n=24 Participants
|
|
Height
|
168.6 centimeters
STANDARD_DEVIATION 7.98 • n=5 Participants
|
165.3 centimeters
STANDARD_DEVIATION 8.64 • n=7 Participants
|
166.8 centimeters
STANDARD_DEVIATION 11.37 • n=5 Participants
|
166.6 centimeters
STANDARD_DEVIATION 11.86 • n=4 Participants
|
165.1 centimeters
STANDARD_DEVIATION 7.58 • n=21 Participants
|
167.8 centimeters
STANDARD_DEVIATION 9.05 • n=8 Participants
|
164.3 centimeters
STANDARD_DEVIATION 8.74 • n=8 Participants
|
166.3 centimeters
STANDARD_DEVIATION 9.28 • n=24 Participants
|
|
Weight
|
56.4 kilograms
STANDARD_DEVIATION 9.49 • n=5 Participants
|
50.2 kilograms
STANDARD_DEVIATION 7.36 • n=7 Participants
|
57.4 kilograms
STANDARD_DEVIATION 10.58 • n=5 Participants
|
58.7 kilograms
STANDARD_DEVIATION 9.21 • n=4 Participants
|
52.4 kilograms
STANDARD_DEVIATION 7.21 • n=21 Participants
|
53.3 kilograms
STANDARD_DEVIATION 9.41 • n=8 Participants
|
56.1 kilograms
STANDARD_DEVIATION 10.80 • n=8 Participants
|
55.0 kilograms
STANDARD_DEVIATION 9.43 • n=24 Participants
|
|
BMI
|
19.9 kg/m^2
STANDARD_DEVIATION 3.66 • n=5 Participants
|
18.4 kg/m^2
STANDARD_DEVIATION 1.98 • n=7 Participants
|
21.0 kg/m^2
STANDARD_DEVIATION 4.64 • n=5 Participants
|
21.3 kg/m^2
STANDARD_DEVIATION 3.34 • n=4 Participants
|
19.2 kg/m^2
STANDARD_DEVIATION 1.86 • n=21 Participants
|
18.8 kg/m^2
STANDARD_DEVIATION 2.15 • n=8 Participants
|
20.8 kg/m^2
STANDARD_DEVIATION 3.29 • n=8 Participants
|
19.9 kg/m^2
STANDARD_DEVIATION 3.23 • n=24 Participants
|
|
HIV Status
Negative
|
14 participants
n=5 Participants
|
14 participants
n=7 Participants
|
12 participants
n=5 Participants
|
15 participants
n=4 Participants
|
13 participants
n=21 Participants
|
14 participants
n=8 Participants
|
11 participants
n=8 Participants
|
93 participants
n=24 Participants
|
|
HIV Status
Doubtful
|
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=8 Participants
|
1 participants
n=8 Participants
|
1 participants
n=24 Participants
|
|
HIV Status
Positive
|
1 participants
n=5 Participants
|
1 participants
n=7 Participants
|
3 participants
n=5 Participants
|
0 participants
n=4 Participants
|
2 participants
n=21 Participants
|
1 participants
n=8 Participants
|
3 participants
n=8 Participants
|
11 participants
n=24 Participants
|
PRIMARY outcome
Timeframe: 14 consecutive days of treatmentPopulation: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=12 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
Early Bactericidal Activity (EBA) Measured as the Daily Rate of Change in log10 CFUs (Colony Forming Units) of M. Tuberculosis in Sputum on Solid Media (Days 0-14).
|
0.115 log10CFU/ml/day
Interval 0.039 to 0.189
|
0.167 log10CFU/ml/day
Interval 0.075 to 0.257
|
0.076 log10CFU/ml/day
Interval 0.005 to 0.145
|
0.124 log10CFU/ml/day
Interval 0.035 to 0.214
|
0.036 log10CFU/ml/day
Interval -0.026 to 0.099
|
-0.017 log10CFU/ml/day
Interval -0.085 to 0.053
|
0.151 log10CFU/ml/day
Interval 0.071 to 0.232
|
SECONDARY outcome
Timeframe: Days 0-2Population: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=12 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)
|
0.161 log10CFU/ml/day
Interval 0.042 to 0.279
|
0.196 log10CFU/ml/day
Interval 0.061 to 0.33
|
0.062 log10CFU/ml/day
Interval -0.045 to 0.161
|
0.132 log10CFU/ml/day
Interval 0.008 to 0.262
|
0.080 log10CFU/ml/day
Interval -0.028 to 0.209
|
0.018 log10CFU/ml/day
Interval -0.089 to 0.125
|
0.141 log10CFU/ml/day
Interval 0.039 to 0.251
|
SECONDARY outcome
Timeframe: Day 7-14Population: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=12 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)
|
0.085 log10CFU/ml/day
Interval -0.013 to 0.175
|
0.146 log10CFU/ml/day
Interval 0.033 to 0.248
|
0.085 log10CFU/ml/day
Interval -0.006 to 0.182
|
0.118 log10CFU/ml/day
Interval -0.017 to 0.25
|
0.022 log10CFU/ml/day
Interval -0.058 to 0.101
|
-0.038 log10CFU/ml/day
Interval -0.13 to 0.046
|
0.157 log10CFU/ml/day
Interval 0.048 to 0.267
|
SECONDARY outcome
Timeframe: Days 0-14Population: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=14 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)
|
6.3 percentage of change in time/day
Interval 4.2 to 8.6
|
7.0 percentage of change in time/day
Interval 5.1 to 9.4
|
4.3 percentage of change in time/day
Interval 2.9 to 5.7
|
4.9 percentage of change in time/day
Interval 3.3 to 6.8
|
2.0 percentage of change in time/day
Interval 0.8 to 3.4
|
-0.3 percentage of change in time/day
Interval -1.5 to 1.0
|
6.3 percentage of change in time/day
Interval 4.8 to 7.6
|
SECONDARY outcome
Timeframe: Day 0-2Population: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=14 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)
|
10.6 percentage of change in time/day
Interval 8.0 to 13.3
|
13.2 percentage of change in time/day
Interval 9.0 to 17.9
|
6.0 percentage of change in time/day
Interval 4.2 to 7.8
|
9.1 percentage of change in time/day
Interval 6.5 to 12.2
|
4.7 percentage of change in time/day
Interval 2.4 to 7.5
|
2.1 percentage of change in time/day
Interval -0.5 to 5.0
|
12.9 percentage of change in time/day
Interval 8.9 to 17.9
|
SECONDARY outcome
Timeframe: Days 7-14Population: Efficacy population: all patients included in the safety population for whom corresponding efficacy data were available and had no major protocol violations/deviations defined as protocol violations/deviations affecting the integrity of the efficacy data
Outcome measures
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=14 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=13 Participants
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 Participants
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=14 Participants
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 Participants
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)
|
3.6 percentage of change in time/day
Interval 1.5 to 6.2
|
4.5 percentage of change in time/day
Interval 2.9 to 6.2
|
3.1 percentage of change in time/day
Interval 1.7 to 4.7
|
3.0 percentage of change in time/day
Interval 1.5 to 4.9
|
0.8 percentage of change in time/day
Interval -0.7 to 2.3
|
-1.3 percentage of change in time/day
Interval -2.9 to 0.4
|
4.4 percentage of change in time/day
Interval 2.9 to 5.8
|
Adverse Events
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
Serious events: 0 serious events
Other events: 11 other events
Deaths: 0 deaths
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
Serious events: 0 serious events
Other events: 9 other events
Deaths: 0 deaths
TMC207, PA-824 and Clofazimine (J-PA-C)
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Pyrazinamide (Z)
Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths
Clofazimine (C)
Serious events: 1 serious events
Other events: 9 other events
Deaths: 0 deaths
Rifafour
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 participants at risk
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=15 participants at risk
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 participants at risk
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Vascular disorders
Deep Vein Thrombosis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
Other adverse events
| Measure |
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, PA-824 and Pyrazinamide (J-PA-Z)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
TMC207, PA-824 and Clofazimine (J-PA-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
PA-824 (PA): 200 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
TMC207, Pyrazinamide and Clofazimine (J-Z-C)
n=15 participants at risk
TMC207 (J): 400 mg on Day 1; 300 mg on Day 2; and 200 mg on Days 3 to 14
pyrazinamide (Z): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Pyrazinamide (Z)
n=15 participants at risk
pyrazinamide (Z): 1500 mg on Days 1 to 14
|
Clofazimine (C)
n=15 participants at risk
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
|
Rifafour
n=15 participants at risk
Rifafour on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|---|---|
|
Investigations
QT prolonged
|
20.0%
3/15
|
0.00%
0/15
|
20.0%
3/15
|
13.3%
2/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
ALT Increased
|
13.3%
2/15
|
13.3%
2/15
|
0.00%
0/15
|
13.3%
2/15
|
6.7%
1/15
|
20.0%
3/15
|
6.7%
1/15
|
|
Investigations
AST Increased
|
6.7%
1/15
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
13.3%
2/15
|
0.00%
0/15
|
|
Investigations
GGT increased
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
Transaminases increased
|
0.00%
0/15
|
6.7%
1/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
Amylase increased
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
Blood Creatine Phosphokinase Increased
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
Blood Urea Increased
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Investigations
Hepatic Enzyme Increased
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Diarrhoea
|
13.3%
2/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
6.7%
1/15
|
6.7%
1/15
|
|
Gastrointestinal disorders
Abdominal Pain
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Gastrointestinal disorders
Nausea
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15
|
|
Gastrointestinal disorders
Abdominal Tenderness
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Epigastric Discomfort
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Salivary Gland Enlargement
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Gastrointestinal disorders
Toothache
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Nervous system disorders
Headache
|
6.7%
1/15
|
13.3%
2/15
|
6.7%
1/15
|
6.7%
1/15
|
20.0%
3/15
|
6.7%
1/15
|
6.7%
1/15
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15
|
|
Nervous system disorders
Somnolence
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash Papular
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Skin Discolouration
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Dry Skin
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Rash Pruritic
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Skin and subcutaneous tissue disorders
Skin Hyperpigmentation
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Respiratory, thoracic and mediastinal disorders
Haemoptysis
|
0.00%
0/15
|
6.7%
1/15
|
13.3%
2/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Respiratory, thoracic and mediastinal disorders
Pleuritic Pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
13.3%
2/15
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Cardiac disorders
Atrioventricular Block First Degree
|
13.3%
2/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Cardiac disorders
Bundle Branch Block Right
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Eye disorders
Photophobia
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
13.3%
2/15
|
13.3%
2/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Eye disorders
Lacrimation Increased
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Infections and infestations
Tooth Abcess
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Herpes Zoster
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Infections and infestations
Oral Candidiasis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Infections and infestations
Tinea Versicolour
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Infections and infestations
Vulvovaginal Candidiasis
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
General disorders
Vessel Puncture Site Pain
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
|
General disorders
Oedema, peripheral
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Foreign Body
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Injury, poisoning and procedural complications
Procedural Dizziness
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Decreased Appetite
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
|
Vascular disorders
Blood Pressure inadequately controlled
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
|
Vascular disorders
Pallor
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
|
Ear and labyrinth disorders
Cerumen Impaction
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/15
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/15
|
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 The investigator or any Sub-Investigator shall submit any oral or written publication or abstract concerning this study to the Sponsor not less than thirty (30) days prior to submission to any journal, other publication or meeting, for review and removal of confidential information.
- Publication restrictions are in place
Restriction type: OTHER