Trial Outcomes & Findings for Various Doses and Durations of Linezolid Plus Bedaquiline & Pretomanid in Participants With Drug Resistant Tuberculosis (NCT NCT03086486)
NCT ID: NCT03086486
Last Updated: 2023-06-29
Results Overview
Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
181 participants
Primary outcome timeframe
26 weeks
Results posted on
2023-06-29
Participant Flow
A total of 248 participants were screened for the trial, of whom 67 failed screening, 181 were randomized, and 169 completed treatment.
Participant milestones
| Measure |
1200mg L x 26 Weeks + Pa + B
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
45
|
46
|
45
|
45
|
|
Overall Study
COMPLETED
|
44
|
42
|
43
|
40
|
|
Overall Study
NOT COMPLETED
|
1
|
4
|
2
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
Baseline characteristics by cohort
| Measure |
1200mg L x 26 Weeks + Pa + B
n=45 Participants
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=46 Participants
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=45 Participants
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=45 Participants
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=181 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
37.4 years
n=45 Participants
|
35.1 years
n=46 Participants
|
39.2 years
n=45 Participants
|
36.8 years
n=45 Participants
|
37.1 years
n=181 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=45 Participants
|
16 Participants
n=46 Participants
|
14 Participants
n=45 Participants
|
14 Participants
n=45 Participants
|
59 Participants
n=181 Participants
|
|
Sex: Female, Male
Male
|
30 Participants
n=45 Participants
|
30 Participants
n=46 Participants
|
31 Participants
n=45 Participants
|
31 Participants
n=45 Participants
|
122 Participants
n=181 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Race (NIH/OMB)
Black or African American
|
11 Participants
n=45 Participants
|
18 Participants
n=46 Participants
|
21 Participants
n=45 Participants
|
16 Participants
n=45 Participants
|
66 Participants
n=181 Participants
|
|
Race (NIH/OMB)
White
|
34 Participants
n=45 Participants
|
28 Participants
n=46 Participants
|
24 Participants
n=45 Participants
|
29 Participants
n=45 Participants
|
115 Participants
n=181 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Region of Enrollment
South Africa
|
11 Participants
n=45 Participants
|
18 Participants
n=46 Participants
|
21 Participants
n=45 Participants
|
16 Participants
n=45 Participants
|
66 Participants
n=181 Participants
|
|
Region of Enrollment
Moldova
|
2 Participants
n=45 Participants
|
4 Participants
n=46 Participants
|
1 Participants
n=45 Participants
|
3 Participants
n=45 Participants
|
10 Participants
n=181 Participants
|
|
Region of Enrollment
Georgia
|
13 Participants
n=45 Participants
|
8 Participants
n=46 Participants
|
5 Participants
n=45 Participants
|
8 Participants
n=45 Participants
|
34 Participants
n=181 Participants
|
|
Region of Enrollment
Russia
|
19 Participants
n=45 Participants
|
16 Participants
n=46 Participants
|
18 Participants
n=45 Participants
|
18 Participants
n=45 Participants
|
71 Participants
n=181 Participants
|
|
Height
|
173.2 cm
n=45 Participants
|
170.2 cm
n=46 Participants
|
171.2 cm
n=45 Participants
|
171.2 cm
n=45 Participants
|
171.4 cm
n=181 Participants
|
|
Weight
|
62.8 kg
n=45 Participants
|
62.1 kg
n=46 Participants
|
63.1 kg
n=45 Participants
|
64.5 kg
n=45 Participants
|
63.1 kg
n=181 Participants
|
|
BMI
|
20.8 kg/m^2
n=45 Participants
|
21.3 kg/m^2
n=46 Participants
|
21.3 kg/m^2
n=45 Participants
|
21.9 kg/m^2
n=45 Participants
|
21.3 kg/m^2
n=181 Participants
|
|
HIV Status
Positive
|
9 Participants
n=45 Participants
|
9 Participants
n=46 Participants
|
9 Participants
n=45 Participants
|
9 Participants
n=45 Participants
|
36 Participants
n=181 Participants
|
|
HIV Status
Negative
|
36 Participants
n=45 Participants
|
37 Participants
n=46 Participants
|
36 Participants
n=45 Participants
|
36 Participants
n=45 Participants
|
145 Participants
n=181 Participants
|
|
Smoking
Never
|
20 Participants
n=45 Participants
|
15 Participants
n=46 Participants
|
16 Participants
n=45 Participants
|
17 Participants
n=45 Participants
|
68 Participants
n=181 Participants
|
|
Smoking
Current
|
15 Participants
n=45 Participants
|
22 Participants
n=46 Participants
|
17 Participants
n=45 Participants
|
12 Participants
n=45 Participants
|
66 Participants
n=181 Participants
|
|
Smoking
Former
|
10 Participants
n=45 Participants
|
9 Participants
n=46 Participants
|
12 Participants
n=45 Participants
|
16 Participants
n=45 Participants
|
47 Participants
n=181 Participants
|
|
Alcohol Use
Never
|
21 Participants
n=45 Participants
|
13 Participants
n=46 Participants
|
18 Participants
n=45 Participants
|
11 Participants
n=45 Participants
|
63 Participants
n=181 Participants
|
|
Alcohol Use
Current
|
8 Participants
n=45 Participants
|
8 Participants
n=46 Participants
|
8 Participants
n=45 Participants
|
10 Participants
n=45 Participants
|
34 Participants
n=181 Participants
|
|
Alcohol Use
Former
|
16 Participants
n=45 Participants
|
25 Participants
n=46 Participants
|
19 Participants
n=45 Participants
|
24 Participants
n=45 Participants
|
84 Participants
n=181 Participants
|
|
Karnofsky performance status
100
|
1 Participants
n=45 Participants
|
1 Participants
n=46 Participants
|
2 Participants
n=45 Participants
|
4 Participants
n=45 Participants
|
8 Participants
n=181 Participants
|
|
Karnofsky performance status
90
|
28 Participants
n=45 Participants
|
30 Participants
n=46 Participants
|
29 Participants
n=45 Participants
|
26 Participants
n=45 Participants
|
113 Participants
n=181 Participants
|
|
Karnofsky performance status
80
|
13 Participants
n=45 Participants
|
13 Participants
n=46 Participants
|
10 Participants
n=45 Participants
|
11 Participants
n=45 Participants
|
47 Participants
n=181 Participants
|
|
Karnofsky performance status
70
|
3 Participants
n=45 Participants
|
2 Participants
n=46 Participants
|
4 Participants
n=45 Participants
|
4 Participants
n=45 Participants
|
13 Participants
n=181 Participants
|
|
Karnofsky performance status
60 or below
|
0 Participants
n=45 Participants
|
0 Participants
n=46 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=45 Participants
|
0 Participants
n=181 Participants
|
|
Current Tuberculosis (TB) type
Multi Drug Resistant (MDR) TB (nonresponsive)
|
2 Participants
n=45 Participants
|
5 Participants
n=46 Participants
|
2 Participants
n=45 Participants
|
3 Participants
n=45 Participants
|
12 Participants
n=181 Participants
|
|
Current Tuberculosis (TB) type
Multi Drug Resistant (MDR) TB (treatment-intolerant)
|
3 Participants
n=45 Participants
|
1 Participants
n=46 Participants
|
2 Participants
n=45 Participants
|
3 Participants
n=45 Participants
|
9 Participants
n=181 Participants
|
|
Current Tuberculosis (TB) type
Pre-Extensively Drug Resistant (Pre-XDR) TB
|
19 Participants
n=45 Participants
|
22 Participants
n=46 Participants
|
22 Participants
n=45 Participants
|
22 Participants
n=45 Participants
|
85 Participants
n=181 Participants
|
|
Current Tuberculosis (TB) type
Extensively Drug Resistant (XDR) TB
|
21 Participants
n=45 Participants
|
18 Participants
n=46 Participants
|
19 Participants
n=45 Participants
|
17 Participants
n=45 Participants
|
75 Participants
n=181 Participants
|
|
History of Tuberculosis (TB)
Drug Sensitive (DS) TB
|
16 participants
n=45 Participants
|
13 participants
n=46 Participants
|
18 participants
n=45 Participants
|
7 participants
n=45 Participants
|
54 participants
n=181 Participants
|
|
History of Tuberculosis (TB)
Mono Resistant TB
|
0 participants
n=45 Participants
|
0 participants
n=46 Participants
|
1 participants
n=45 Participants
|
1 participants
n=45 Participants
|
2 participants
n=181 Participants
|
|
History of Tuberculosis (TB)
MDR TB
|
20 participants
n=45 Participants
|
23 participants
n=46 Participants
|
21 participants
n=45 Participants
|
25 participants
n=45 Participants
|
89 participants
n=181 Participants
|
|
History of Tuberculosis (TB)
Pre-XDR TB
|
6 participants
n=45 Participants
|
5 participants
n=46 Participants
|
6 participants
n=45 Participants
|
7 participants
n=45 Participants
|
24 participants
n=181 Participants
|
|
History of Tuberculosis (TB)
XDR TB
|
25 participants
n=45 Participants
|
28 participants
n=46 Participants
|
28 participants
n=45 Participants
|
25 participants
n=45 Participants
|
106 participants
n=181 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
No AFB seen
|
23 Participants
n=45 Participants
|
24 Participants
n=46 Participants
|
23 Participants
n=45 Participants
|
20 Participants
n=45 Participants
|
90 Participants
n=181 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
Scanty positive
|
11 Participants
n=45 Participants
|
4 Participants
n=46 Participants
|
8 Participants
n=45 Participants
|
5 Participants
n=45 Participants
|
28 Participants
n=181 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
1+
|
4 Participants
n=45 Participants
|
7 Participants
n=46 Participants
|
4 Participants
n=45 Participants
|
6 Participants
n=45 Participants
|
21 Participants
n=181 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
2+
|
6 Participants
n=45 Participants
|
6 Participants
n=46 Participants
|
3 Participants
n=45 Participants
|
4 Participants
n=45 Participants
|
19 Participants
n=181 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
3+
|
1 Participants
n=45 Participants
|
5 Participants
n=46 Participants
|
7 Participants
n=45 Participants
|
10 Participants
n=45 Participants
|
23 Participants
n=181 Participants
|
|
Time to positive at baseline
|
14.3 days
n=30 Participants • Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
|
11.3 days
n=32 Participants • Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
|
14.0 days
n=33 Participants • Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
|
12.5 days
n=36 Participants • Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
|
13.0 days
n=131 Participants • Only participants who were positive at baseline in liquid culture MGIT. Positive culture at screening not required per protocol.
|
|
Chest x-ray at Screening
Normal
|
2 Participants
n=45 Participants
|
2 Participants
n=46 Participants
|
1 Participants
n=45 Participants
|
2 Participants
n=45 Participants
|
7 Participants
n=181 Participants
|
|
Chest x-ray at Screening
Abnormal
|
43 Participants
n=45 Participants
|
44 Participants
n=46 Participants
|
44 Participants
n=45 Participants
|
43 Participants
n=45 Participants
|
174 Participants
n=181 Participants
|
|
Chest X-ray Cavities at Screening
None
|
18 Participants
n=45 Participants
|
21 Participants
n=46 Participants
|
12 Participants
n=45 Participants
|
18 Participants
n=45 Participants
|
69 Participants
n=181 Participants
|
|
Chest X-ray Cavities at Screening
Unilateral
|
22 Participants
n=45 Participants
|
21 Participants
n=46 Participants
|
20 Participants
n=45 Participants
|
21 Participants
n=45 Participants
|
84 Participants
n=181 Participants
|
|
Chest X-ray Cavities at Screening
Bilateral
|
5 Participants
n=45 Participants
|
4 Participants
n=46 Participants
|
13 Participants
n=45 Participants
|
6 Participants
n=45 Participants
|
28 Participants
n=181 Participants
|
PRIMARY outcome
Timeframe: 26 weeksPopulation: Participants were considered unassessable and therefore excluded from the Modified Intent to Treat (MITT) population if they were late exclusions, lost to follow-up, reinfected with a different strain of TB, withdrawn during the Follow-up Period, or died during the treatment period.
Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment
Outcome measures
| Measure |
1200mg L x 26 Weeks + Pa + B
n=44 Participants
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=45 Participants
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=45 Participants
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=44 Participants
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=178 Participants
Total Study Population
|
|---|---|---|---|---|---|
|
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment
Favorable
|
41 Participants
|
40 Participants
|
41 Participants
|
37 Participants
|
159 Participants
|
|
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 26 Weeks After the End of Treatment
Unfavorable
|
3 Participants
|
5 Participants
|
4 Participants
|
7 Participants
|
19 Participants
|
SECONDARY outcome
Timeframe: 78 weeksPopulation: Participants were considered unassessable and therefore excluded from the Modified Intent to Treat (MITT) population if they were late exclusions, lost to follow-up, reinfected with a different strain of TB, withdrawn during the Follow-up Period, or died during the treatment period.
Unfavourable status: 1. Participants not classified as having achieved or maintained culture negative status when last seen 2. Participants previously classified as having culture negative status who, following the end of treatment, have two positive cultures without an intervening negative culture 3. Participants who had a positive culture not followed by at least two negative cultures when last seen 4. Participants dying from any cause during treatment, except from violent or accidental cause, not including suicide 5. Participants definitely or possibly dying from TB related cause during the follow-up phase 6. Participants requiring an extension of their treatment beyond that permitted by the protocol a restart or a change of treatment for any reason except reinfection or pregnancy 7. Participants who have had surgery and the resected tissue is cultured and is positive for MTB 8. Participants lost to follow up or withdrawn from the study before the end of treatment
Outcome measures
| Measure |
1200mg L x 26 Weeks + Pa + B
n=43 Participants
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=44 Participants
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=45 Participants
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=44 Participants
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=176 Participants
Total Study Population
|
|---|---|---|---|---|---|
|
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.
Favorable
|
40 Participants
|
39 Participants
|
40 Participants
|
35 Participants
|
154 Participants
|
|
Incidence of Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) Through Follow up Until 78 Weeks After the End of Treatment.
Unfavorable
|
3 Participants
|
5 Participants
|
5 Participants
|
9 Participants
|
22 Participants
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants in the MITT population who were culture positive during the baseline period were assessable. Unassessable Includes participants not positive at baseline and/or unassessable in the MITT population.
Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures. Note: * Culture conversion requires at least 2 consecutive culture negative/positive samples at least 7 days apart. * Participants who are documented at a visit as unable to produce sputum and who are clinically considered to be responding well to treatment will be considered to be culture negative at that visit.
Outcome measures
| Measure |
1200mg L x 26 Weeks + Pa + B
n=30 Participants
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=32 Participants
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=33 Participants
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=35 Participants
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=130 Participants
Total Study Population
|
|---|---|---|---|---|---|
|
Time to Sputum Culture Conversion to Negative Status Through the Treatment Period
|
4 weeks
Interval 2.0 to 8.0
|
4 weeks
Interval 2.0 to 8.0
|
6 weeks
Interval 3.0 to 6.0
|
6 weeks
Interval 3.0 to 10.0
|
6 weeks
Interval 3.0 to 8.0
|
SECONDARY outcome
Timeframe: End of Treatment, 26 weeksPopulation: The participant numbers for inclusion in analysis are those assessable participants with a positive culture status at baseline, not including those who withdrew or were lost to contact during treatment at or before Week 26.
Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with tuberculosis can no longer produce tuberculosis cell cultures.
Outcome measures
| Measure |
1200mg L x 26 Weeks + Pa + B
n=29 Participants
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=29 Participants
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=32 Participants
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=32 Participants
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=122 Participants
Total Study Population
|
|---|---|---|---|---|---|
|
Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline
Negative
|
29 Participants
|
28 Participants
|
31 Participants
|
31 Participants
|
119 Participants
|
|
Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline
Positive
|
0 Participants
|
1 Participants
|
1 Participants
|
1 Participants
|
3 Participants
|
|
Sputum Culture Conversion to Negative Status at End of Treatment for Those Positive at Baseline
Died
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
Adverse Events
1200mg L x 26 Weeks + Pa + B
Serious events: 3 serious events
Other events: 40 other events
Deaths: 0 deaths
1200 mg L x 9 Weeks + Pa + B
Serious events: 4 serious events
Other events: 41 other events
Deaths: 1 deaths
600 mg L x 26 Weeks + Pa + B
Serious events: 1 serious events
Other events: 39 other events
Deaths: 0 deaths
600 mg L x 9 Weeks + Pa + B
Serious events: 3 serious events
Other events: 36 other events
Deaths: 0 deaths
Total
Serious events: 11 serious events
Other events: 156 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
1200mg L x 26 Weeks + Pa + B
n=45 participants at risk
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=46 participants at risk
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=45 participants at risk
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=45 participants at risk
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=181 participants at risk
Total Study Population
|
|---|---|---|---|---|---|
|
Eye disorders
Optic neuropathy
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
1.1%
2/181 • Number of events 2 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Infections and infestations
Hepatitis B
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Infections and infestations
Tertiary syphilis
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Infections and infestations
Tuberculosis
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Injury, poisoning and procedural complications
Wound haemorrhage
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Brain oedema
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Optic neuritis
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Psychiatric disorders
Alcoholic psychosis
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary fibrosis
|
2.2%
1/45 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.00%
0/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
0.55%
1/181 • Number of events 1 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
Other adverse events
| Measure |
1200mg L x 26 Weeks + Pa + B
n=45 participants at risk
2 linezolid 600 mg active tablets once daily for 26 weeks plus 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
1200 mg L x 9 Weeks + Pa + B
n=46 participants at risk
2 linezolid 600 mg active tablets once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 26 Weeks + Pa + B
n=45 participants at risk
1 linezolid 600 mg active tablet once daily for 26 weeks, 1 placebo linezolid 600 mg tablet once daily for 26 weeks, 1 placebo linezolid 300 mg half tablet once daily for 26 weeks plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
600 mg L x 9 Weeks + Pa + B
n=45 participants at risk
1 linezolid 600 mg active tablets once daily for 8 weeks, 1 placebo linezolid 600 mg half tablet once daily for 9 weeks, 1 placebo linezolid 300 mg half tablet once daily for 9 weeks (for Weeks 1-9); 2 placebo linezolid 600 mg tablets once daily for 17 weeks, 1 placebo linezolid 300 mg half tablet once daily for 17 weeks (for Weeks 10-26) plus; bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks plus; pretomanid 200 mg once daily for 26 weeks
|
Total
n=181 participants at risk
Total Study Population
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Dyspepsia
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
5.0%
9/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Infections and infestations
Upper respiratory tract infection
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.7%
4/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
5.0%
9/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Gastrointestinal disorders
Nausea
|
13.3%
6/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
10.9%
5/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.3%
15/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
5.0%
9/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
13.0%
6/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.8%
16/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Gastrointestinal disorders
Diarrhoea
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.6%
12/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Blood and lymphatic system disorders
Anaemia
|
15.6%
7/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
7.7%
14/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Investigations
Hepatic enzyme increased
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
17.4%
8/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.0%
20/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Investigations
Transaminases increased
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
13.3%
6/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.8%
16/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Headache
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
10.9%
5/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
7.2%
13/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Hypoaesthesia
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.7%
4/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
7.7%
14/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Paraesthesia
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.1%
11/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
20.0%
9/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
13.0%
6/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.6%
21/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Skin and subcutaneous tissue disorders
Dermatitis acneiform
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.5%
3/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
7.2%
13/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.3%
2/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
5.5%
10/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Skin and subcutaneous tissue disorders
Rash papular
|
6.7%
3/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.7%
4/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
5.5%
10/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
|
Vascular disorders
Hypertension
|
11.1%
5/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
2.2%
1/46 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
4.4%
2/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
8.9%
4/45 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
6.6%
12/181 • 28 weeks
All listed adverse events (AEs) are treatment emergent adverse events (TEAE) which are defined as AEs that started or worsened at or after the first administration of IMP up to and including 14 days after the last administration of IMP.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Institution and Principal Investigator shall not publish, present or use the Study Data for its own instruction, research or publication without the prior express written consent of Sponsor. Because the Study is funded, in whole or in part, by the Bill and Melinda Gates Foundation (the "Foundation"), all peer-reviewed published research relating to the Study must comply with the Foundation's Open Access Policy.
- Publication restrictions are in place
Restriction type: OTHER