Trial Outcomes & Findings for Evaluation of 8 Weeks of Treatment With the Combination of Moxifloxacin, PA-824 and Pyrazinamide in Patients With Drug Sensitive and Multi Drug-Resistant Pulmonary Tuberculosis (TB) (NC-002) (NCT NCT01498419)
NCT ID: NCT01498419
Last Updated: 2018-06-28
Results Overview
The primary efficacy endpoint was bactericidal activity characterized by the daily rate of change in mean log10CFU counts during 8 weeks of treatment (bactericidal activity assessed by CFU on solid media for days 0-56).
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
207 participants
Primary outcome timeframe
8 weeks
Results posted on
2018-06-28
Participant Flow
Participant milestones
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
60
|
62
|
59
|
26
|
|
Overall Study
COMPLETED
|
42
|
39
|
41
|
7
|
|
Overall Study
NOT COMPLETED
|
18
|
23
|
18
|
19
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Evaluation of 8 Weeks of Treatment With the Combination of Moxifloxacin, PA-824 and Pyrazinamide in Patients With Drug Sensitive and Multi Drug-Resistant Pulmonary Tuberculosis (TB) (NC-002)
Baseline characteristics by cohort
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=62 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Total
n=207 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
29.5 years
STANDARD_DEVIATION 10.63 • n=5 Participants
|
30.9 years
STANDARD_DEVIATION 8.96 • n=7 Participants
|
30.4 years
STANDARD_DEVIATION 9.75 • n=5 Participants
|
32.4 years
STANDARD_DEVIATION 9.75 • n=4 Participants
|
30.6 years
STANDARD_DEVIATION 9.77 • n=21 Participants
|
|
Sex: Female, Male
Female
|
22 Participants
n=5 Participants
|
22 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
10 Participants
n=4 Participants
|
72 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
38 Participants
n=5 Participants
|
40 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
135 Participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Black
|
43 participants
n=5 Participants
|
46 participants
n=7 Participants
|
43 participants
n=5 Participants
|
15 participants
n=4 Participants
|
147 participants
n=21 Participants
|
|
Race/Ethnicity, Customized
Mixed Ethnic
|
17 participants
n=5 Participants
|
16 participants
n=7 Participants
|
16 participants
n=5 Participants
|
11 participants
n=4 Participants
|
60 participants
n=21 Participants
|
|
Weight
|
54.7 kilograms
STANDARD_DEVIATION 8.72 • n=5 Participants
|
57.6 kilograms
STANDARD_DEVIATION 10.09 • n=7 Participants
|
54.7 kilograms
STANDARD_DEVIATION 7.95 • n=5 Participants
|
57.9 kilograms
STANDARD_DEVIATION 10.61 • n=4 Participants
|
56 kilograms
STANDARD_DEVIATION 9.25 • n=21 Participants
|
|
HIV Status
Positive
|
12 participants
n=5 Participants
|
8 participants
n=7 Participants
|
13 participants
n=5 Participants
|
7 participants
n=4 Participants
|
40 participants
n=21 Participants
|
|
HIV Status
Negative
|
48 participants
n=5 Participants
|
53 participants
n=7 Participants
|
45 participants
n=5 Participants
|
18 participants
n=4 Participants
|
164 participants
n=21 Participants
|
|
HIV Status
Indeterminate
|
0 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
HIV Status
Missing
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
1 participants
n=4 Participants
|
2 participants
n=21 Participants
|
|
Pyrazinamide susceptibility
Resistant
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
17 participants
n=4 Participants
|
20 participants
n=21 Participants
|
|
Pyrazinamide susceptibility
Sensitive
|
60 participants
n=5 Participants
|
59 participants
n=7 Participants
|
58 participants
n=5 Participants
|
9 participants
n=4 Participants
|
186 participants
n=21 Participants
|
|
Pyrazinamide susceptibility
Missing
|
0 participants
n=5 Participants
|
1 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
|
Moxifloxacin susceptibility
Resistant
|
0 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
1 participants
n=4 Participants
|
4 participants
n=21 Participants
|
|
Moxifloxacin susceptibility
Sensitive
|
56 participants
n=5 Participants
|
58 participants
n=7 Participants
|
57 participants
n=5 Participants
|
25 participants
n=4 Participants
|
196 participants
n=21 Participants
|
|
Moxifloxacin susceptibility
No Result
|
3 participants
n=5 Participants
|
2 participants
n=7 Participants
|
1 participants
n=5 Participants
|
0 participants
n=4 Participants
|
6 participants
n=21 Participants
|
|
Moxifloxacin susceptibility
Unclear
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
0 participants
n=5 Participants
|
0 participants
n=4 Participants
|
1 participants
n=21 Participants
|
PRIMARY outcome
Timeframe: 8 weeksPopulation: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 173.
The primary efficacy endpoint was bactericidal activity characterized by the daily rate of change in mean log10CFU counts during 8 weeks of treatment (bactericidal activity assessed by CFU on solid media for days 0-56).
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=56 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=54 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=54 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=9 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
The Rate of Change in Colony Forming Units (CFUs) Using Non-linear Mixed Effects Modeling of the Serial Sputum Colony Counts (SSCC) Over 8 Weeks of Treatment.
|
0.133 log10CFU/ml/day
Interval 0.109 to 0.155
|
0.155 log10CFU/ml/day
Interval 0.133 to 0.178
|
0.112 log10CFU/ml/day
Interval 0.093 to 0.131
|
0.117 log10CFU/ml/day
Interval 0.07 to 0.174
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants included for this outcome was 206.
liquid culture = Mycobacteria growth indicator tube (MGIT) Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=61 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Liquid Media
|
42.0 days
Interval 35.0 to
There were not enough conversion events to determine the 75th percentile
|
49.0 days
Interval 41.0 to 56.0
|
56.0 days
Interval 43.0 to
There were not enough conversion events to determine the 75th percentile
|
56.0 days
Interval 45.0 to
There were not enough conversion events to determine the 75th percentile
|
SECONDARY outcome
Timeframe: Day 57 after eight weeks of daily treatmentPopulation: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. Participants included in this outcome had a valid, non-contaminated culture from the sample acquired on Day 57.
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. (Day 57)
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=35 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=35 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=32 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=8 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Solid Media
|
82.9 percentage of participants
|
94.3 percentage of participants
|
87.5 percentage of participants
|
62.5 percentage of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 179.
Measurement of TTP in liquid culture media Mycobacteria growth indicator tube (MGIT) using standard procedures
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=55 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=57 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=58 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=9 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
The Rate of Change in Time to Sputum Culture Positivity (TTP) Through 8 Weeks in the MGIT System in Sputum Over 8 Weeks in Participants as Derived From a Non-linear Regression Model.
|
0.020 log10hours/day
Interval 0.015 to 0.025
|
0.020 log10hours/day
Interval 0.016 to 0.024
|
0.017 log10hours/day
Interval 0.013 to 0.021
|
0.015 log10hours/day
Interval -0.001 to 0.031
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: The Safety population was analyzed for this outcome.
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=62 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Percentage of Participants Who Discontinue Due to an Adverse Event in Each Experimental Arm.
|
13 percentage of participants
|
19 percentage of participants
|
12 percentage of participants
|
12 percentage of participants
|
SECONDARY outcome
Timeframe: 8 weeksPopulation: The efficacy analysis population contained patients included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. The number of participants analyzed for this outcome was 206.
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=61 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Time to Sputum Conversion Using Data From Weekly Cultures Through 8 Weeks on Solid Media
|
28.0 days
Interval 14.0 to 35.0
|
28.0 days
Interval 21.0 to 35.0
|
35.0 days
Interval 21.0 to 49.0
|
35.0 days
Interval 24.5 to 56.0
|
SECONDARY outcome
Timeframe: Day 57 after eight weeks of daily treatmentPopulation: The efficacy analysis population contained participants included in the safety analysis population for whom efficacy data were available and who had no major protocol violations that could affect the integrity of the efficacy data. Participants included in this outcome had a valid, non-contaminated culture from the sample acquired on Day 57.
Sputum culture conversion is defined as a change from a positive growth of M. tuberculosis in a sputum sample to negative M. tuberculosis growth sputum sample in patients with pulmonary TB. This was measured at visit 24(Day 57).
Outcome measures
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=35 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=35 Participants
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=37 Participants
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=8 Participants
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Percentage of Patients With Sputum Culture Conversion at 8 Weeks on Liquid Media
|
65.7 percentage of patients
|
71.4 percentage of patients
|
37.8 percentage of patients
|
50.0 percentage of patients
|
Adverse Events
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
Serious events: 1 serious events
Other events: 52 other events
Deaths: 0 deaths
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
Serious events: 7 serious events
Other events: 57 other events
Deaths: 0 deaths
Drug Sensitive: Rifafour
Serious events: 1 serious events
Other events: 50 other events
Deaths: 0 deaths
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
Serious events: 0 serious events
Other events: 23 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 participants at risk
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=62 participants at risk
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 participants at risk
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 participants at risk
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
General disorders
Death - Cause Unknown
|
1.7%
1/60
|
0.00%
0/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Hepatobiliary disorders
Drug-Induced Hepatitis
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Cardiac disorders
Cardiac Arrhythmia (2nd degree AV block)
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
Hyperuriceamia
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Musculoskeletal and connective tissue disorders
Closed Tibia Plateau Fracture-Left Knee Joint
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Hepatobiliary disorders
Elevated Liver Enzymes
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Congenital, familial and genetic disorders
Epileptic Seizures
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/60
|
1.6%
1/62
|
0.00%
0/59
|
0.00%
0/26
|
|
Hepatobiliary disorders
Liver Drug-Induced Toxicity
|
0.00%
0/60
|
0.00%
0/62
|
1.7%
1/59
|
0.00%
0/26
|
Other adverse events
| Measure |
Drug Sensitive: M (400 mg) Pa (100 mg) Z (1500 mg)
n=60 participants at risk
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 100 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: M (400 mg) Pa (200 mg) Z (1500 mg)
n=62 participants at risk
Drug Sensitive Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
Drug Sensitive: Rifafour
n=59 participants at risk
Drug Sensitive Participants received Rifafour e-275 once daily for 8 weeks. Daily dose dependent on weight as follows: 30-37kg: two tablets, 38-54kg: three tablets, 55-70kg: four tablets: 71kg and over: five tablets
|
Multi Drug-Resistant: M (400 mg) Pa (200 mg) Z (1500 mg)
n=26 participants at risk
Multi Drug-Resistant Participants received moxifloxacin (M) (one 400 mg tablet), pretomanid (Pa-824; Pa) (one 200 mg tablet), and pyrazinamide (Z) (three 500 mg tablets) once daily for 8 weeks
|
|---|---|---|---|---|
|
Metabolism and nutrition disorders
HYPERURICAEMIA
|
28.3%
17/60
|
27.4%
17/62
|
28.8%
17/59
|
30.8%
8/26
|
|
Metabolism and nutrition disorders
HYPONATRAEMIA
|
13.3%
8/60
|
8.1%
5/62
|
13.6%
8/59
|
0.00%
0/26
|
|
Metabolism and nutrition disorders
HYPERGLYCAEMIA
|
6.7%
4/60
|
3.2%
2/62
|
5.1%
3/59
|
11.5%
3/26
|
|
Metabolism and nutrition disorders
ENZYME ABNORMALITY
|
3.3%
2/60
|
6.5%
4/62
|
6.8%
4/59
|
3.8%
1/26
|
|
Metabolism and nutrition disorders
HYPOALBUMINAEMIA
|
6.7%
4/60
|
3.2%
2/62
|
8.5%
5/59
|
0.00%
0/26
|
|
Gastrointestinal disorders
NAUSEA
|
23.3%
14/60
|
12.9%
8/62
|
11.9%
7/59
|
30.8%
8/26
|
|
Gastrointestinal disorders
VOMITING
|
11.7%
7/60
|
11.3%
7/62
|
11.9%
7/59
|
15.4%
4/26
|
|
Gastrointestinal disorders
DIARRHOEA
|
6.7%
4/60
|
4.8%
3/62
|
5.1%
3/59
|
11.5%
3/26
|
|
Gastrointestinal disorders
ABDOMINAL PAIN
|
10.0%
6/60
|
3.2%
2/62
|
5.1%
3/59
|
3.8%
1/26
|
|
Musculoskeletal and connective tissue disorders
ARTHRALGIA
|
33.3%
20/60
|
29.0%
18/62
|
18.6%
11/59
|
0.00%
0/26
|
|
Skin and subcutaneous tissue disorders
PRURITUS
|
8.3%
5/60
|
3.2%
2/62
|
8.5%
5/59
|
3.8%
1/26
|
|
Hepatobiliary disorders
LIVER DISORDER
|
26.7%
16/60
|
22.6%
14/62
|
15.3%
9/59
|
11.5%
3/26
|
|
Blood and lymphatic system disorders
LEUKOCYTOSIS
|
8.3%
5/60
|
6.5%
4/62
|
5.1%
3/59
|
0.00%
0/26
|
|
Nervous system disorders
DIZZINESS
|
10.0%
6/60
|
12.9%
8/62
|
3.4%
2/59
|
3.8%
1/26
|
|
Nervous system disorders
HEADACHE
|
10.0%
6/60
|
9.7%
6/62
|
3.4%
2/59
|
7.7%
2/26
|
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