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Trial record 60 of 76 for:    "Bacterial Infectious Disease" | "Polyestradiol phosphate"

Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis With(J-M-Pa-Z) (NC-001)

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ClinicalTrials.gov Identifier: NCT01215851
Recruitment Status : Completed
First Posted : October 7, 2010
Results First Posted : April 1, 2016
Last Update Posted : February 28, 2017
Sponsor:
Information provided by (Responsible Party):
Global Alliance for TB Drug Development

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Pulmonary Tuberculosis
Interventions Drug: PA-824
Drug: Pyrazinamide
Drug: TMC207
Drug: Rifafour
Drug: Moxifloxacin
Enrollment 85
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description 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 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 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 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 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 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
Period Title: Treatment Period
Started 15 15 15 15 10 15
Completed 14 14 14 12 10 14
Not Completed 1 1 1 3 0 1
Reason Not Completed
Adverse Event             1             1             1             3             0             1
Period Title: Follow up Period
Started 14 14 14 12 10 14
Completed 14 14 14 12 10 13
Not Completed 0 0 0 0 0 1
Reason Not Completed
Lost to Follow-up             0             0             0             0             0             1
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824 Total
Hide Arm/Group Description 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 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 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 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 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 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 of all reporting groups
Overall Number of Baseline Participants 15 15 15 15 10 15 85
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 15 participants 15 participants 10 participants 15 participants 85 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
15
 100.0%
15
 100.0%
15
 100.0%
15
 100.0%
10
 100.0%
15
 100.0%
85
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 15 participants 15 participants 10 participants 15 participants 85 participants
31.3  (11.60) 29.1  (8.67) 29.7  (8.93) 28.3  (9.34) 27.0  (6.63) 33.3  (8.47) 30.0  (9.13)
Gender  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 15 participants 15 participants 10 participants 15 participants 85 participants
Female
4
  26.7%
3
  20.0%
4
  26.7%
3
  20.0%
4
  40.0%
4
  26.7%
22
  25.9%
Male
11
  73.3%
12
  80.0%
11
  73.3%
12
  80.0%
6
  60.0%
11
  73.3%
63
  74.1%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
South Africa Number Analyzed 15 participants 15 participants 15 participants 15 participants 10 participants 15 participants 85 participants
15 15 15 15 10 15 85
1.Primary Outcome
Title 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).
Hide Description 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.
Time Frame 14 consecutive days of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description:
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 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 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 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 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 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
Overall Number of Participants Analyzed 14 15 14 13 10 14
Mean (Standard Deviation)
Unit of Measure: log10CFU/ml/day
0.061  (0.068) 0.131  (0.102) 0.154  (0.040) 0.233  (0.128) 0.140  (0.094) 0.114  (0.050)
2.Secondary Outcome
Title 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).
Hide Description 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.
Time Frame Day 0-2
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description:
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 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 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 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 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 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
Overall Number of Participants Analyzed 15 15 15 15 10 14
Mean (Standard Deviation)
Unit of Measure: log10CFU/ml/day
-0.022  (0.121) 0.079  (0.167) 0.170  (0.082) 0.315  (0.133) 0.177  (0.188) 0.114  (0.149)
3.Secondary Outcome
Title 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).
Hide Description 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.
Time Frame Day 2-14
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description:
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
MC207 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 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 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 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 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
Overall Number of Participants Analyzed 14 15 14 13 10 14
Mean (Standard Deviation)
Unit of Measure: log10CFU/ml/day
0.076  (0.069) 0.143  (0.109) 0.148  (0.043) 0.222  (0.130) 0.135  (0.103) 0.114  (0.047)
4.Secondary Outcome
Title 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).
Hide Description 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.
Time Frame Day 7-14
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description:
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 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 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 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 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 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
Overall Number of Participants Analyzed 14 15 14 13 10 14
Mean (Standard Deviation)
Unit of Measure: log10CFU/ml/day
0.123  (0.097) 0.152  (0.120) 0.124  (0.080) 0.175  (0.146) 0.136  (0.102) 0.114  (0.069)
5.Secondary Outcome
Title Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)
Hide Description 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).
Time Frame 14 Days
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description:
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 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 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 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 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 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
Overall Number of Participants Analyzed 14 15 14 13 10 15
Mean (Standard Deviation)
Unit of Measure: time (h) to positive per day
5.414  (3.523) 9.970  (6.987) 8.805  (3.468) 18.482  (22.582) 11.841  (3.932) 5.855  (2.785)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Hide Arm/Group Description TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide placebo TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus pyrazinamide (dosed by weight) PA-824 200mg and pyrazinamide (dosed by weight)and moxifloxacin placebo PA-824 200 mg and pyrazinamide (dosed by weight) and moxifloxacin 400 mg Rifafour e-275 275 mg TMC207 700 mg Day 1; 500mg Day 2; 400mg Days 3-14 plus PA-824 200 mg
All-Cause Mortality
TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
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 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      0/15 (0.00%)      0/15 (0.00%)      1/15 (6.67%)      0/10 (0.00%)      1/15 (6.67%)    
Infections and infestations             
Worsening of Pulmonary Tuberculosis  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 1/15 (6.67%)  1
Neurocysticercosis  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, Medra 13.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
TMC207 TMC207 and Pyrazinamide PA-824 and Pyrazinamide PA-824 and Moxifloxacin and Pyrazinamide Rifafour e-275 mg TMC207 and PA-824
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/15 (46.67%)      6/15 (40.00%)      7/15 (46.67%)      8/15 (53.33%)      5/10 (50.00%)      9/15 (60.00%)    
Eye disorders             
Conjunctival hemorrhage  1  1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Eyelid edema  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 1/15 (6.67%)  1
Lenticular opacities  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Gastrointestinal disorders             
Vomiting  1  3/15 (20.00%)  3 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 2/10 (20.00%)  2 1/15 (6.67%)  1
Nausea  1  2/15 (13.33%)  2 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Abdominal pain  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 0/15 (0.00%)  0
Abdominal pain lower  1  1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Abdominal pain upper  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Diarrhea  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Dyspepsia  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Toothache  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
General disorders             
Hyperthermia  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 1/15 (6.67%)  1
Infections and infestations             
Furuncle  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/10 (10.00%)  1 0/15 (0.00%)  0
Nasopharyngitis  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Tooth abscess  1  1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Vulvovaginal candidiasis  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Injury, poisoning and procedural complications             
Skin laceration  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 0/15 (0.00%)  0
Investigations             
Alanine aminotransferase increased  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 2/15 (13.33%)  2 0/10 (0.00%)  0 2/15 (13.33%)  2
Gamma-glutamyltransferase increased  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 0/15 (0.00%)  0
Aspartate aminotransferase increased  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Blood alkaline phosphatase increased  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Blood amylase increased  1  1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
electrocardiogram QT prolonged  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 0/15 (0.00%)  0
Metabolism and nutrition disorders             
Type I diabetes mellitus  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 1/15 (6.67%)  1
Musculoskeletal and connective tissue disorders             
Back pain  1  0/15 (0.00%)  0 1/15 (6.67%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0 1/10 (10.00%)  1 0/15 (0.00%)  0
Arthralgia  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/10 (10.00%)  1 0/15 (0.00%)  0
Bursitis  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Muscle spasms  1  1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Myalgia  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Pain in extremity  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Nervous system disorders             
Headache  1  2/15 (13.33%)  3 2/15 (13.33%)  2 2/15 (13.33%)  2 2/15 (13.33%)  3 1/10 (10.00%)  1 3/15 (20.00%)  3
Reproductive system and breast disorders             
Dysmenorrhoea  1  0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Respiratory, thoracic and mediastinal disorders             
Hemoptysis  1  1/15 (6.67%)  1 1/15 (6.67%)  1 0/15 (0.00%)  0 0/15 (0.00%)  0 0/10 (0.00%)  0 2/15 (13.33%)  2
Skin and subcutaneous tissue disorders             
Rash papular  1  0/15 (0.00%)  0 0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/10 (0.00%)  0 1/15 (6.67%)  1
Pruritis  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Rash maculo-papular  1  0/15 (0.00%)  0 0/15 (0.00%)  0 1/15 (6.67%)  1 0/15 (0.00%)  0 0/10 (0.00%)  0 0/15 (0.00%)  0
Indicates events were collected by systematic assessment
1
Term from vocabulary, Medra 13.1
With the small sample, individual results can influence overall results. Comparison between groups and studies is difficult. The ability to assign AEs to a particular compound is limited. The value of EBA studies for predicting relapse is uncertain.
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.
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.
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: NCT01215851     History of Changes
Other Study ID Numbers: NC-001-(J-M-Pa-Z)
First Submitted: October 5, 2010
First Posted: October 7, 2010
Results First Submitted: January 7, 2013
Results First Posted: April 1, 2016
Last Update Posted: February 28, 2017