Trial Outcomes & Findings for PA-824-CL-007: Phase IIa Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis (NCT NCT00567840)
NCT ID: NCT00567840
Last Updated: 2017-05-15
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
69 participants
Primary outcome timeframe
Day 0 and Day 14
Results posted on
2017-05-15
Participant Flow
Participant milestones
| Measure |
PA-824 200 mg
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
15
|
15
|
16
|
15
|
8
|
|
Overall Study
COMPLETED
|
13
|
15
|
15
|
14
|
8
|
|
Overall Study
NOT COMPLETED
|
2
|
0
|
1
|
1
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
PA-824-CL-007: Phase IIa Evaluation of Early Bactericidal Activity in Pulmonary Tuberculosis
Baseline characteristics by cohort
| Measure |
PA-824 200 mg
n=15 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=15 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=16 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=15 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 Participants
Rifafour e-275 on Days 1 to 14, dosed by weight
|
Total
n=69 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
30.5 years
STANDARD_DEVIATION 8.50 • n=5 Participants
|
30.6 years
STANDARD_DEVIATION 9.72 • n=7 Participants
|
31.7 years
STANDARD_DEVIATION 8.86 • n=5 Participants
|
32.4 years
STANDARD_DEVIATION 11.51 • n=4 Participants
|
21.9 years
STANDARD_DEVIATION 3.44 • n=21 Participants
|
30.2 years
STANDARD_DEVIATION 9.48 • n=8 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
31 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
9 Participants
n=5 Participants
|
9 Participants
n=4 Participants
|
4 Participants
n=21 Participants
|
38 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Black
|
10 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
3 Participants
n=21 Participants
|
35 Participants
n=8 Participants
|
|
Race/Ethnicity, Customized
Mixed Ethnic
|
5 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
5 Participants
n=21 Participants
|
34 Participants
n=8 Participants
|
|
Weight
|
55.3 kg
STANDARD_DEVIATION 8.58 • n=5 Participants
|
55.9 kg
STANDARD_DEVIATION 10.51 • n=7 Participants
|
52.5 kg
STANDARD_DEVIATION 9.82 • n=5 Participants
|
53.5 kg
STANDARD_DEVIATION 8.48 • n=4 Participants
|
48.0 kg
STANDARD_DEVIATION 8.70 • n=21 Participants
|
53.6 kg
STANDARD_DEVIATION 9.36 • n=8 Participants
|
|
Body Mass Index (BMI)
|
20.19 kg/m^2
STANDARD_DEVIATION 4.031 • n=5 Participants
|
20.09 kg/m^2
STANDARD_DEVIATION 3.899 • n=7 Participants
|
19.09 kg/m^2
STANDARD_DEVIATION 2.562 • n=5 Participants
|
19.41 kg/m^2
STANDARD_DEVIATION 3.058 • n=4 Participants
|
17.53 kg/m^2
STANDARD_DEVIATION 1.785 • n=21 Participants
|
19.43 kg/m^2
STANDARD_DEVIATION 3.294 • n=8 Participants
|
PRIMARY outcome
Timeframe: Day 0 and Day 14Population: 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.
Outcome measures
| Measure |
PA-824 200 mg
n=12 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=14 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=15 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=11 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=7 Participants
Rifafour e-275 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).
|
0.106 log10 CFU/ml
Standard Deviation 0.049
|
0.107 log10 CFU/ml
Standard Deviation 0.053
|
0.091 log10 CFU/ml
Standard Deviation 0.083
|
0.088 log10 CFU/ml
Standard Deviation 0.084
|
0.148 log10 CFU/ml
Standard Deviation 0.055
|
SECONDARY outcome
Timeframe: Day 0 and Day 2Population: 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.
Outcome measures
| Measure |
PA-824 200 mg
n=15 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=13 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=15 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=15 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 Participants
Rifafour e-275 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 0-2).
|
0.109 log10 CFU/ml
Standard Deviation 0.487
|
0.096 log10 CFU/ml
Standard Deviation 0.226
|
0.025 log10 CFU/ml
Standard Deviation 0.340
|
-0.035 log10 CFU/ml
Standard Deviation 0.420
|
0.403 log10 CFU/ml
Standard Deviation 0.290
|
SECONDARY outcome
Timeframe: Day 2 and Day 14Population: 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.
Outcome measures
| Measure |
PA-824 200 mg
n=12 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=13 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=14 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=11 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=7 Participants
Rifafour e-275 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 2-14).
|
0.106 log10 CFU/ml
Standard Deviation 0.063
|
0.113 log10 CFU/ml
Standard Deviation 0.079
|
0.095 log10 CFU/ml
Standard Deviation 0.062
|
0.113 log10 CFU/ml
Standard Deviation 0.099
|
0.112 log10 CFU/ml
Standard Deviation 0.050
|
SECONDARY outcome
Timeframe: Day 0 and Day 14Outcome measures
| Measure |
PA-824 200 mg
n=12 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=14 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=13 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=12 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 Participants
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-14)
|
3.818 hours/day
Standard Deviation 2.327
|
4.776 hours/day
Standard Deviation 2.879
|
4.865 hours/day
Standard Deviation 3.461
|
4.440 hours/day
Standard Deviation 2.169
|
9.741 hours/day
Standard Deviation 5.249
|
SECONDARY outcome
Timeframe: Day 0 and Day 2Outcome measures
| Measure |
PA-824 200 mg
n=13 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=13 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=11 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=15 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 Participants
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 0-2)
|
1.115 hours/day
Standard Deviation 15.256
|
5.788 hours/day
Standard Deviation 12.173
|
2.795 hours/day
Standard Deviation 9.230
|
1.400 hours/day
Standard Deviation 7.659
|
24.125 hours/day
Standard Deviation 12.794
|
SECONDARY outcome
Timeframe: Day 2 and Day 14Outcome measures
| Measure |
PA-824 200 mg
n=11 Participants
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=13 Participants
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=12 Participants
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=12 Participants
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 Participants
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
EBA Expressed as the Change in Time to Positive (TTP) Signal in Liquid Culture for M. Tuberculosis (Days 2-14) Show Description: [Not Specified]
|
3.833 hours/day
Standard Deviation 2.954
|
5.09 hours/day
Standard Deviation 2.768
|
4.069 hours/day
Standard Deviation 1.916
|
4.868 hours/day
Standard Deviation 3.224
|
7.344 hours/day
Standard Deviation 4.66
|
Adverse Events
PA-824 200 mg
Serious events: 1 serious events
Other events: 6 other events
Deaths: 0 deaths
PA-824 600 mg
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
PA-824 1000 mg
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
PA-824 1200 mg
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Rifafour
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
PA-824 200 mg
n=15 participants at risk
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=15 participants at risk
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=16 participants at risk
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=15 participants at risk
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 participants at risk
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
6.7%
1/15
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
12.5%
1/8
|
Other adverse events
| Measure |
PA-824 200 mg
n=15 participants at risk
PA-824: 200 mg per day for 14 consecutive days
|
PA-824 600 mg
n=15 participants at risk
PA-824: 600 mg per day for 14 consecutive days
|
PA-824 1000 mg
n=16 participants at risk
PA-824: 1000 mg per day for 14 consecutive days
|
PA-824 1200 mg
n=15 participants at risk
PA-824: 1200 mg per day for 14 consecutive days
|
Rifafour
n=8 participants at risk
Rifafour e-275 on Days 1 to 14, dosed by weight
|
|---|---|---|---|---|---|
|
Psychiatric disorders
Confusional State
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/15
|
0.00%
0/15
|
6.2%
1/16 • Number of events 1
|
0.00%
0/15
|
12.5%
1/8 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
6.2%
1/16 • Number of events 2
|
0.00%
0/15
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Pruritus Generalized
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Rash Maculo-Papular
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/15
|
0.00%
0/15
|
6.2%
1/16 • Number of events 1
|
13.3%
2/15 • Number of events 2
|
0.00%
0/8
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
13.3%
2/15 • Number of events 2
|
0.00%
0/8
|
|
Gastrointestinal disorders
Abdominal Pain
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Gastrointestinal disorders
Lip Ulceration
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Gastrointestinal disorders
Toothache
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Cardiac disorders
Atrioventricular Block First Degree
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
12.5%
1/8 • Number of events 1
|
|
Cardiac disorders
Atrioventricular Block Second Degree
|
6.7%
1/15 • Number of events 2
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Cardiac disorders
Wolff-Parkinson-White Syndrome
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
0.00%
0/15
|
0.00%
0/15
|
6.2%
1/16 • Number of events 1
|
0.00%
0/15
|
0.00%
0/8
|
|
Blood and lymphatic system disorders
Iron Deficiency Anaemia
|
0.00%
0/15
|
6.7%
1/15 • Number of events 1
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Investigations
Electrocardiogram QT corrected Interval Prolonged
|
0.00%
0/15
|
0.00%
0/15
|
6.2%
1/16 • Number of events 1
|
0.00%
0/15
|
0.00%
0/8
|
|
Investigations
Hepatic Enzyme Increased
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Musculoskeletal and connective tissue disorders
Pain in the Extremity
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Nervous system disorders
Dizziness
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
|
Nervous system disorders
Dizziness Postural
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Eye disorders
Eye Pruritus
|
0.00%
0/15
|
0.00%
0/15
|
6.2%
1/16 • Number of events 1
|
0.00%
0/15
|
0.00%
0/8
|
|
General disorders
Chest Pain
|
6.7%
1/15 • Number of events 1
|
0.00%
0/15
|
0.00%
0/16
|
0.00%
0/15
|
0.00%
0/8
|
|
Infections and infestations
Urinary Tract Infection
|
0.00%
0/15
|
0.00%
0/15
|
0.00%
0/16
|
6.7%
1/15 • Number of events 1
|
0.00%
0/8
|
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