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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Global Alliance for TB Drug Development
ClinicalTrials.gov Identifier:
NCT01215851
First received: October 5, 2010
Last updated: July 12, 2016
Last verified: March 2016
Results First Received: January 7, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Pulmonary Tuberculosis
Interventions: Drug: PA-824
Drug: Pyrazinamide
Drug: TMC207
Drug: Rifafour
Drug: Moxifloxacin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

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

Participant Flow for 2 periods

Period 1:   Treatment Period
    TMC207   TMC207 and Pyrazinamide   PA-824 and Pyrazinamide   PA-824 and Moxifloxacin and Pyrazinamide   Rifafour e-275 mg   TMC207 and PA-824
STARTED   15   15   15   15   10   15 
COMPLETED   14   14   14   12   10   14 
NOT COMPLETED   1   1   1   3   0   1 
Adverse Event                1                1                1                3                0                1 

Period 2:   Follow up Period
    TMC207   TMC207 and Pyrazinamide   PA-824 and Pyrazinamide   PA-824 and Moxifloxacin and Pyrazinamide   Rifafour e-275 mg   TMC207 and PA-824
STARTED   14   14   14   12   10   14 
COMPLETED   14   14   14   12   10   13 
NOT COMPLETED   0   0   0   0   0   1 
Lost to Follow-up                0                0                0                0                0                1 



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

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

Baseline Measures
   TMC207   TMC207 and Pyrazinamide   PA-824 and Pyrazinamide   PA-824 and Moxifloxacin and Pyrazinamide   Rifafour e-275 mg   TMC207 and PA-824   Total 
Overall Participants Analyzed 
[Units: Participants]
 15   15   15   15   10   15   85 
Age 
[Units: Participants]
             
<=18 years   0   0   0   0   0   0   0 
Between 18 and 65 years   15   15   15   15   10   15   85 
>=65 years   0   0   0   0   0   0   0 
Age 
[Units: Years]
Mean (Standard Deviation)
 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 
[Units: Participants]
             
Female   4   3   4   3   4   4   22 
Male   11   12   11   12   6   11   63 
Region of Enrollment 
[Units: Participants]
             
South Africa   15   15   15   15   10   15   85 


  Outcome Measures
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1.  Primary:   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).   [ Time Frame: 14 consecutive days of treatment ]

2.  Secondary:   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).   [ Time Frame: Day 0-2 ]

3.  Secondary:   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).   [ Time Frame: Day 2-14 ]

4.  Secondary:   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).   [ Time Frame: Day 7-14 ]

5.  Secondary:   Rate of Change in Time to Sputum Culture Positivity (TTP)(Hours) in Liquid Culture Media (Days 0-14)   [ Time Frame: 14 Days ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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.


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Dan Everitt, MD Senior Medical Officer
Organization: Global Alliance for TB Drug Development
phone: 484-919-0017
e-mail: dan.everitt@tballiance.org


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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)
Study First Received: October 5, 2010
Results First Received: January 7, 2013
Last Updated: July 12, 2016