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Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With Clofazimine (C)-TMC207 (J)-PA-824 (Pa)-Pyrazinamide (Z) (NC-003)

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ClinicalTrials.gov Identifier: NCT01691534
Recruitment Status : Completed
First Posted : September 24, 2012
Results First Posted : December 13, 2016
Last Update Posted : December 13, 2016
Sponsor:
Information provided by (Responsible Party):
Global Alliance for TB Drug Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Tuberculosis
Interventions Drug: TMC207 (J)
Drug: PA-824 (PA)
Drug: pyrazinamide (Z)
Drug: clofazimine (C)
Drug: Rifafour
Enrollment 105
Recruitment Details  
Pre-assignment Details  
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description

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 (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 (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 (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): 1500 mg on Days 1 to 14 clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14 Rifafour on Days 1 to 14, dosed by weight
Period Title: Overall Study
Started 15 15 15 15 15 15 15
Completed 15 14 14 14 15 14 14
Not Completed 0 1 1 1 0 1 1
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour Total
Hide Arm/Group Description

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 (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 (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 (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): 1500 mg on Days 1 to 14 clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14 Rifafour on Days 1 to 14, dosed by weight Total of all reporting groups
Overall Number of Baseline Participants 15 15 15 15 15 15 15 105
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
35.5  (8.74) 33.4  (14.22) 33.3  (11.15) 30.9  (13.12) 32.4  (11.44) 28.4  (8.77) 34.3  (10.25) 32.6  (11.15)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
Female
3
  20.0%
3
  20.0%
8
  53.3%
6
  40.0%
6
  40.0%
6
  40.0%
8
  53.3%
40
  38.1%
Male
12
  80.0%
12
  80.0%
7
  46.7%
9
  60.0%
9
  60.0%
9
  60.0%
7
  46.7%
65
  61.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
Black 9 5 6 8 8 6 9 51
Asian 0 0 0 0 1 0 0 1
White 0 1 0 0 0 0 0 1
Mixed Ethnic 6 9 9 7 6 9 6 52
Height  
Mean (Standard Deviation)
Unit of measure:  Centimeters
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
168.6  (7.98) 165.3  (8.64) 166.8  (11.37) 166.6  (11.86) 165.1  (7.58) 167.8  (9.05) 164.3  (8.74) 166.3  (9.28)
Weight  
Mean (Standard Deviation)
Unit of measure:  Kilograms
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
56.4  (9.49) 50.2  (7.36) 57.4  (10.58) 58.7  (9.21) 52.4  (7.21) 53.3  (9.41) 56.1  (10.80) 55.0  (9.43)
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
19.9  (3.66) 18.4  (1.98) 21.0  (4.64) 21.3  (3.34) 19.2  (1.86) 18.8  (2.15) 20.8  (3.29) 19.9  (3.23)
HIV Status  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 15 participants 105 participants
Negative 14 14 12 15 13 14 11 93
Doubtful 0 0 0 0 0 0 1 1
Positive 1 1 3 0 2 1 3 11
1.Primary Outcome
Title 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).
Hide Description [Not Specified]
Time Frame 14 consecutive days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 12 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: log10CFU/ml/day
0.115
(0.039 to 0.189)
0.167
(0.075 to 0.257)
0.076
(0.005 to 0.145)
0.124
(0.035 to 0.214)
0.036
(-0.026 to 0.099)
-0.017
(-0.085 to 0.053)
0.151
(0.071 to 0.232)
2.Secondary Outcome
Title EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 0-2)
Hide Description [Not Specified]
Time Frame Days 0-2
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 12 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: log10CFU/ml/day
0.161
(0.042 to 0.279)
0.196
(0.061 to 0.330)
0.062
(-0.045 to 0.161)
0.132
(0.008 to 0.262)
0.080
(-0.028 to 0.209)
0.018
(-0.089 to 0.125)
0.141
(0.039 to 0.251)
3.Secondary Outcome
Title EBA Measured as the Daily Rate of Change in log10 CFUs of M. Tuberculosis in Sputum on Solid Media (Days 7-14)
Hide Description [Not Specified]
Time Frame Day 7-14
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 12 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: log10CFU/ml/day
0.085
(-0.013 to 0.175)
0.146
(0.033 to 0.248)
0.085
(-0.006 to 0.182)
0.118
(-0.017 to 0.250)
0.022
(-0.058 to 0.101)
-0.038
(-0.130 to 0.046)
0.157
(0.048 to 0.267)
4.Secondary Outcome
Title EBA Expressed as the Daily Percentage Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)
Hide Description [Not Specified]
Time Frame Days 0-14
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-1414
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 14 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: percentage of change in time/day
6.3
(4.2 to 8.6)
7.0
(5.1 to 9.4)
4.3
(2.9 to 5.7)
4.9
(3.3 to 6.8)
2.0
(0.8 to 3.4)
-0.3
(-1.5 to 1.0)
6.3
(4.8 to 7.6)
5.Secondary Outcome
Title EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Day 0-2)
Hide Description [Not Specified]
Time Frame Day 0-2
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 14 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: percentage of change in time/day
10.6
(8.0 to 13.3)
13.2
(9.0 to 17.9)
6.0
(4.2 to 7.8)
9.1
(6.5 to 12.2)
4.7
(2.4 to 7.5)
2.1
(-0.5 to 5.0)
12.9
(8.9 to 17.9)
6.Secondary Outcome
Title EBA Expressed as the Daily Percentage Change in TTP Signal in Liquid Culture for M. Tuberculosis (Days 7-14)
Hide Description [Not Specified]
Time Frame Days 7-14
Hide Outcome Measure Data
Hide Analysis Population Description
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
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description:

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 (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 (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 (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): 1500 mg on Days 1 to 14
clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14
Rifafour on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 14 15 13 15 14 15
Mean (95% Confidence Interval)
Unit of Measure: percentage of change in time/day
3.6
(1.5 to 6.2)
4.5
(2.9 to 6.2)
3.1
(1.7 to 4.7)
3.0
(1.5 to 4.9)
0.8
(-0.7 to 2.3)
-1.3
(-2.9 to 0.4)
4.4
(2.9 to 5.8)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Hide Arm/Group Description

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 (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 (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 (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): 1500 mg on Days 1 to 14 clofazimine (C): 300 mg on Days 1 to 3 and 100 mg on Days 4-14 Rifafour on Days 1 to 14, dosed by weight
All-Cause Mortality
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)   0/15 (0.00%)   0/15 (0.00%)   0/15 (0.00%)   0/15 (0.00%)   1/15 (6.67%)   0/15 (0.00%) 
Blood and lymphatic system disorders               
Anaemia  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Infections and infestations               
Gastroenteritis  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Vascular disorders               
Deep Vein Thrombosis  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC207, PA-824, Pyrazinamide and Clofazimine (J-PA-Z-C) TMC207, PA-824 and Pyrazinamide (J-PA-Z) TMC207, PA-824 and Clofazimine (J-PA-C) TMC207, Pyrazinamide and Clofazimine (J-Z-C) Pyrazinamide (Z) Clofazimine (C) Rifafour
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/15 (73.33%)   9/15 (60.00%)   8/15 (53.33%)   10/15 (66.67%)   10/15 (66.67%)   9/15 (60.00%)   8/15 (53.33%) 
Cardiac disorders               
Atrioventricular Block First Degree  2/15 (13.33%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Bundle Branch Block Right  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Ear and labyrinth disorders               
Cerumen Impaction  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Eye disorders               
Photophobia  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  2/15 (13.33%)  0/15 (0.00%)  1/15 (6.67%) 
Lacrimation Increased  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Gastrointestinal disorders               
Diarrhoea  2/15 (13.33%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Vomiting  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  1/15 (6.67%)  1/15 (6.67%) 
Abdominal Pain  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Nausea  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/15 (13.33%) 
Abdominal Tenderness  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Constipation  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Epigastric Discomfort  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Salivary Gland Enlargement  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Toothache  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
General disorders               
Vessel Puncture Site Pain 1 [1]  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Oedema, peripheral 1 [1]  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Infections and infestations               
Tooth Abcess  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Herpes Zoster  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Oral Candidiasis  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Tinea Versicolour  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Vulvovaginal Candidiasis  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Injury, poisoning and procedural complications               
Foreign Body  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Ligament Sprain  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Procedural Dizziness  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Investigations               
QT prolonged 1 [2]  3/15 (20.00%)  0/15 (0.00%)  3/15 (20.00%)  2/15 (13.33%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
ALT Increased 1 [3]  2/15 (13.33%)  2/15 (13.33%)  0/15 (0.00%)  2/15 (13.33%)  1/15 (6.67%)  3/15 (20.00%)  1/15 (6.67%) 
AST Increased 1 [3]  1/15 (6.67%)  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  2/15 (13.33%)  0/15 (0.00%) 
GGT increased 1 [3]  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Transaminases increased 1 [3]  0/15 (0.00%)  1/15 (6.67%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Amylase increased 1 [3]  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Blood Creatine Phosphokinase Increased  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Blood Urea Increased  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Hepatic Enzyme Increased  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Metabolism and nutrition disorders               
Decreased Appetite  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Hyperkalaemia  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Musculoskeletal and connective tissue disorders               
Arthralgia  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Back Pain  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Musculoskeletal Pain  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Neck Pain  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Nervous system disorders               
Headache  1/15 (6.67%)  2/15 (13.33%)  1/15 (6.67%)  1/15 (6.67%)  3/15 (20.00%)  1/15 (6.67%)  1/15 (6.67%) 
Dizziness  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/15 (13.33%) 
Somnolence  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Respiratory, thoracic and mediastinal disorders               
Haemoptysis  0/15 (0.00%)  1/15 (6.67%)  2/15 (13.33%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Pleuritic Pain  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  2/15 (13.33%) 
Epistaxis  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%) 
Skin and subcutaneous tissue disorders               
Rash Papular  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  1/15 (6.67%)  1/15 (6.67%)  0/15 (0.00%) 
Skin Discolouration  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  2/15 (13.33%)  0/15 (0.00%) 
Pruritus  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Dry Skin  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
Rash  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Rash Pruritic  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Skin Hyperpigmentation  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Urticaria  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%) 
Vascular disorders               
Blood Pressure inadequately controlled  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%) 
Pallor  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  0/15 (0.00%)  1/15 (6.67%)  0/15 (0.00%) 
1
Term from vocabulary, MedDRA (15.1)
[1]
and Administration site conditions
[2]
Electrocardiogram
[3]
Laboratory toxicities
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Name/Title: Daniel E. Everitt, MD, Vice President and Senior Medical Officer
Organization: Global Alliance for TB Drug Development
Phone: 212-227-7540
Responsible Party: Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier: NCT01691534     History of Changes
Other Study ID Numbers: NC-003-(C-J-Pa-Z)
First Submitted: September 20, 2012
First Posted: September 24, 2012
Results First Submitted: October 19, 2016
Results First Posted: December 13, 2016
Last Update Posted: December 13, 2016