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PA-824-CL-007: Phase IIa Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00567840
Recruitment Status : Completed
First Posted : December 5, 2007
Results First Posted : April 4, 2017
Last Update Posted : May 15, 2017
Sponsor:
Information provided by:
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
Intervention Drug: PA-824
Enrollment 69
Recruitment Details  
Pre-assignment Details  
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description PA-824: 200 mg per day for 14 consecutive days PA-824: 600 mg per day for 14 consecutive days PA-824: 1000 mg per day for 14 consecutive days PA-824: 1200 mg per day for 14 consecutive days Rifafour e-275 on Days 1 to 14, dosed by weight
Period Title: Overall Study
Started 15 15 16 15 8
Completed 13 15 15 14 8
Not Completed 2 0 1 1 0
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour Total
Hide Arm/Group Description PA-824: 200 mg per day for 14 consecutive days PA-824: 600 mg per day for 14 consecutive days PA-824: 1000 mg per day for 14 consecutive days PA-824: 1200 mg per day for 14 consecutive days Rifafour e-275 on Days 1 to 14, dosed by weight Total of all reporting groups
Overall Number of Baseline Participants 15 15 16 15 8 69
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 15 participants 16 participants 15 participants 8 participants 69 participants
30.5  (8.50) 30.6  (9.72) 31.7  (8.86) 32.4  (11.51) 21.9  (3.44) 30.2  (9.48)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 16 participants 15 participants 8 participants 69 participants
Female
8
  53.3%
6
  40.0%
7
  43.8%
6
  40.0%
4
  50.0%
31
  44.9%
Male
7
  46.7%
9
  60.0%
9
  56.3%
9
  60.0%
4
  50.0%
38
  55.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 15 participants 16 participants 15 participants 8 participants 69 participants
Black
10
  66.7%
6
  40.0%
8
  50.0%
8
  53.3%
3
  37.5%
35
  50.7%
Mixed Ethnic
5
  33.3%
9
  60.0%
8
  50.0%
7
  46.7%
5
  62.5%
34
  49.3%
Weight  
Mean (Standard Deviation)
Unit of measure:  Kg
Number Analyzed 15 participants 15 participants 16 participants 15 participants 8 participants 69 participants
55.3  (8.58) 55.9  (10.51) 52.5  (9.82) 53.5  (8.48) 48.0  (8.70) 53.6  (9.36)
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 15 participants 15 participants 16 participants 15 participants 8 participants 69 participants
20.19  (4.031) 20.09  (3.899) 19.09  (2.562) 19.41  (3.058) 17.53  (1.785) 19.43  (3.294)
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 Day 0 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Some of the EBA values could not be calculated due to missing results. The number of participants given are the number of participants for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 12 14 15 11 7
Mean (Standard Deviation)
Unit of Measure: log10 CFU/ml
0.106  (0.049) 0.107  (0.053) 0.091  (0.083) 0.088  (0.084) 0.148  (0.055)
2.Secondary 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 0-2).
Hide Description [Not Specified]
Time Frame Day 0 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Some of the EBA values could not be calculated due to missing results. The number of participants given are the number of participants for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 15 13 15 15 8
Mean (Standard Deviation)
Unit of Measure: log10 CFU/ml
0.109  (0.487) 0.096  (0.226) 0.025  (0.340) -0.035  (0.420) 0.403  (0.290)
3.Secondary 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 2-14).
Hide Description [Not Specified]
Time Frame Day 2 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
Some of the EBA values could not be calculated due to missing results. The number of participants given are the number of participants for whom the results were available for this time period and therefore for whom the relevant EBA could be calculated.
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 12 13 14 11 7
Mean (Standard Deviation)
Unit of Measure: log10 CFU/ml
0.106  (0.063) 0.113  (0.079) 0.095  (0.062) 0.113  (0.099) 0.112  (0.050)
4.Secondary Outcome
Title EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)
Hide Description [Not Specified]
Time Frame Day 0 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 12 14 13 12 8
Mean (Standard Deviation)
Unit of Measure: hours/day
3.818  (2.327) 4.776  (2.879) 4.865  (3.461) 4.440  (2.169) 9.741  (5.249)
5.Secondary Outcome
Title EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-2)
Hide Description [Not Specified]
Time Frame Day 0 and Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 13 13 11 15 8
Mean (Standard Deviation)
Unit of Measure: hours/day
1.115  (15.256) 5.788  (12.173) 2.795  (9.230) 1.400  (7.659) 24.125  (12.794)
6.Secondary Outcome
Title EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 2-14) Show Description: [Not Specified]
Hide Description [Not Specified]
Time Frame Day 2 and Day 14
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description:
PA-824: 200 mg per day for 14 consecutive days
PA-824: 600 mg per day for 14 consecutive days
PA-824: 1000 mg per day for 14 consecutive days
PA-824: 1200 mg per day for 14 consecutive days
Rifafour e-275 on Days 1 to 14, dosed by weight
Overall Number of Participants Analyzed 11 13 12 12 8
Mean (Standard Deviation)
Unit of Measure: hours/day
3.833  (2.954) 5.09  (2.768) 4.069  (1.916) 4.868  (3.224) 7.344  (4.66)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Hide Arm/Group Description PA-824: 200 mg per day for 14 consecutive days PA-824: 600 mg per day for 14 consecutive days PA-824: 1000 mg per day for 14 consecutive days PA-824: 1200 mg per day for 14 consecutive days Rifafour e-275 on Days 1 to 14, dosed by weight
All-Cause Mortality
PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Hide Serious Adverse Events
PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/15 (6.67%)      0/15 (0.00%)      0/16 (0.00%)      0/15 (0.00%)      1/8 (12.50%)    
Respiratory, thoracic and mediastinal disorders           
Hemoptysis  1/15 (6.67%)  0/15 (0.00%)  0/16 (0.00%)  0/15 (0.00%)  1/8 (12.50%) 
1
Term from vocabulary, MedDRA 10.1
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
PA-824 200 mg PA-824 600 mg PA-824 1000 mg PA-824 1200 mg Rifafour
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/15 (40.00%)      4/15 (26.67%)      5/16 (31.25%)      7/15 (46.67%)      2/8 (25.00%)    
Blood and lymphatic system disorders           
Iron Deficiency Anaemia  0/15 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Cardiac disorders           
Atrioventricular Block First Degree  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 1/8 (12.50%)  1
Atrioventricular Block Second Degree  1/15 (6.67%)  2 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Wolff-Parkinson-White Syndrome  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Eye disorders           
Eye Pruritus  0/15 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/15 (0.00%)  0 0/8 (0.00%)  0
Gastrointestinal disorders           
Nausea  0/15 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 2/15 (13.33%)  2 0/8 (0.00%)  0
Vomiting  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 2/15 (13.33%)  2 0/8 (0.00%)  0
Abdominal Pain  0/15 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Lip Ulceration  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Toothache  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
General disorders           
Chest Pain 1 [1]  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Infections and infestations           
Urinary Tract Infection  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Investigations           
Electrocardiogram QT corrected Interval Prolonged  0/15 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/15 (0.00%)  0 0/8 (0.00%)  0
Hepatic Enzyme Increased  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Musculoskeletal and connective tissue disorders           
Neck Pain  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Pain in the Extremity  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Nervous system disorders           
Dizziness  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Dizziness Postural  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Psychiatric disorders           
Confusional State  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Respiratory, thoracic and mediastinal disorders           
Hemoptysis  0/15 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/15 (0.00%)  0 0/8 (0.00%)  0
Skin and subcutaneous tissue disorders           
Pruritus  0/15 (0.00%)  0 0/15 (0.00%)  0 1/16 (6.25%)  1 0/15 (0.00%)  0 1/8 (12.50%)  1
Rash  0/15 (0.00%)  0 1/15 (6.67%)  1 1/16 (6.25%)  2 0/15 (0.00%)  0 0/8 (0.00%)  0
Pruritus Generalized  1/15 (6.67%)  1 0/15 (0.00%)  0 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
Rash Maculo-Papular  0/15 (0.00%)  0 0/15 (0.00%)  0 0/16 (0.00%)  0 1/15 (6.67%)  1 0/8 (0.00%)  0
Urticaria  0/15 (0.00%)  0 1/15 (6.67%)  1 0/16 (0.00%)  0 0/15 (0.00%)  0 0/8 (0.00%)  0
1
Term from vocabulary, MedDRA 10.1
[1]
and Administration Site Conditions
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
Layout table for Results Point of Contact information
Name/Title: Daniel E. Everitt, MD, Vice President and Senior Medical Officer
Organization: Global Alliance for TB Drug Development
Phone: 212-227-7540
EMail: Dan.Everitt@tballiance.org
Layout table for additonal information
Responsible Party: Prof. Andreas Diacon, Tiervlei Trial Center, University of Stellenbosch, South Africa
ClinicalTrials.gov Identifier: NCT00567840    
Other Study ID Numbers: PA-824-CL-007
First Submitted: December 4, 2007
First Posted: December 5, 2007
Results First Submitted: February 15, 2017
Results First Posted: April 4, 2017
Last Update Posted: May 15, 2017