Trial Outcomes & Findings for A Trial to Evaluate the Male Reproductive Safety of Pretomanid in Adult Male Participants With Drug Resistant Pulmonary Tuberculosis (NCT NCT04179500)
NCT ID: NCT04179500
Last Updated: 2025-01-17
Results Overview
Change from baseline in total sperm number at 26 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Week 26
Results posted on
2025-01-17
Participant Flow
No pre-assignment events occurred.
Participant milestones
| Measure |
BPaMZ
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|
|
Treatment
STARTED
|
26
|
|
Treatment
COMPLETED
|
22
|
|
Treatment
NOT COMPLETED
|
4
|
|
Follow-up
STARTED
|
22
|
|
Follow-up
COMPLETED
|
18
|
|
Follow-up
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
BPaMZ
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|
|
Treatment
Withdrawal by Subject
|
1
|
|
Treatment
Adverse Event
|
2
|
|
Treatment
pyrazinamide resistance
|
1
|
Baseline Characteristics
participant may have had more than one occurrences of previous TB diagnosis and could select more than one category.
Baseline characteristics by cohort
| Measure |
BPaMZ
n=26 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|
|
Age, Continuous
|
35.4 years
STANDARD_DEVIATION 10.8 • n=26 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=26 Participants
|
|
Sex: Female, Male
Male
|
26 Participants
n=26 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=26 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=26 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=26 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=26 Participants
|
|
Region of Enrollment
South Africa
|
18 participants
n=26 Participants
|
|
Region of Enrollment
Georgia
|
8 participants
n=26 Participants
|
|
Height
|
175.8 cm
STANDARD_DEVIATION 7.3 • n=26 Participants
|
|
Weight
|
62.2 kg
STANDARD_DEVIATION 11.7 • n=26 Participants
|
|
Body Mass Index (BMI)
|
20 Kg/m^2
STANDARD_DEVIATION 3 • n=26 Participants
|
|
HIV Status
Positive
|
8 Participants
n=26 Participants
|
|
HIV Status
Negative
|
18 Participants
n=26 Participants
|
|
Smoking
Never
|
6 Participants
n=26 Participants
|
|
Smoking
Current
|
12 Participants
n=26 Participants
|
|
Smoking
Former
|
8 Participants
n=26 Participants
|
|
Alcohol use
Never
|
4 Participants
n=26 Participants
|
|
Alcohol use
Current
|
12 Participants
n=26 Participants
|
|
Alcohol use
Former
|
10 Participants
n=26 Participants
|
|
Previous Tuberculosis (TB) diagnoses
DS-TB
|
7 Participants
n=26 Participants • participant may have had more than one occurrences of previous TB diagnosis and could select more than one category.
|
|
Previous Tuberculosis (TB) diagnoses
INH Mono-resistant TB
|
2 Participants
n=26 Participants • participant may have had more than one occurrences of previous TB diagnosis and could select more than one category.
|
|
Previous Tuberculosis (TB) diagnoses
RIF mono-resistant TB
|
15 Participants
n=26 Participants • participant may have had more than one occurrences of previous TB diagnosis and could select more than one category.
|
|
Previous Tuberculosis (TB) diagnoses
MDR-TB
|
9 Participants
n=26 Participants • participant may have had more than one occurrences of previous TB diagnosis and could select more than one category.
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
No AFB seen
|
6 Participants
n=26 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
Scanty Positive
|
4 Participants
n=26 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
1+
|
3 Participants
n=26 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
2+
|
3 Participants
n=26 Participants
|
|
Screening smear microscopy for Acid Fast Bacilli (AFB)
3+
|
10 Participants
n=26 Participants
|
|
Time to positivity at baseline
|
9.9 Days
STANDARD_DEVIATION 6.6 • n=21 Participants • Only for those positive (MGIT) at baseline (between Day 1 and Week 4)
|
PRIMARY outcome
Timeframe: Week 26Population: Excludes participants not meeting definition of having received adequate treatment (80% of allocated doses) or with major protocol deviations including participants who did not satisfy entry criteria but were entered anyway; participants who developed withdrawal criteria during the study but were not withdrawn; and participants who received the wrong treatment or incorrect dose..
Change from baseline in total sperm number at 26 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.
Outcome measures
| Measure |
BPaMZ
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Change Form Baseline Total Sperm Count
|
20 10^6 sperm cells/ejaculate
Standard Deviation 97.3
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 12Population: Excludes participants not meeting definition of having received adequate treatment (80% of allocated doses)or with major protocol deviations including participants who did not satisfy entry criteria but were entered anyway; participants who developed withdrawal criteria during the study but were not withdrawn; and participants who received the wrong treatment or incorrect dose.
Change from baseline in total sperm number at 12 weeks of therapy. Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.
Outcome measures
| Measure |
BPaMZ
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Change From Baseline in Total Sperm Count at 12 Weeks
|
4.2 10^6 sperm cells/ejaculate
Standard Deviation 56.8
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline through 44 weeksPopulation: All enrolled participants who completed the 44-week visit.
Change from baseline in total sperm number at 44 weeks (18 months post treatment completion). Total sperm count is calculated by multiplying the sperm cell concentration by the ejaculate volume.
Outcome measures
| Measure |
BPaMZ
n=20 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Change From Baseline Total Sperm Count at 44 Weeks
|
4.4 10^6 sperm cells/ejaculate
Standard Deviation 95.9
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline to Week 78Population: Total assessable. (Excludes participants who were lost to follow-up or with missing data)
(LH) at baseline, 26, 44, and 78 weeks.
Outcome measures
| Measure |
BPaMZ
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
n=19 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
n=18 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Luteinizing Hormone (LH)
|
5.8 IU/mL
Interval 3.9 to 7.0
|
4.6 IU/mL
Interval 3.5 to 5.6
|
3.6 IU/mL
Interval 3.2 to 6.9
|
4.0 IU/mL
Interval 3.5 to 6.2
|
SECONDARY outcome
Timeframe: Baseline to week 78Population: Total assessable. (Excludes participants who were lost to follow-up or with missing data)
FSH at baseline, weeks 26, 44 and 78
Outcome measures
| Measure |
BPaMZ
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
n=19 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
n=18 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
FSH
|
6.6 IU/mL
Interval 3.5 to 10.5
|
6.2 IU/mL
Interval 3.7 to 9.7
|
5.2 IU/mL
Interval 4.4 to 6.8
|
4.6 IU/mL
Interval 2.6 to 5.8
|
SECONDARY outcome
Timeframe: Baseline to 78 weeksPopulation: Total assessable. (Excludes participants who were lost to follow-up or with missing data)
testosterone level at baseline, 26, 44 and 78 weeks.
Outcome measures
| Measure |
BPaMZ
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
n=22 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
n=19 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
n=18 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Testosterone
|
547 ng/dL
Interval 444.0 to 688.0
|
600 ng/dL
Interval 488.0 to 706.0
|
646 ng/dL
Interval 499.0 to 820.0
|
615.5 ng/dL
Interval 504.0 to 797.0
|
SECONDARY outcome
Timeframe: Baseline to 78 weeksPopulation: Total assessable. (Excludes participants who were lost to follow-up or with missing data)
inhibin B at baseline, weeks 26, 44 and 78
Outcome measures
| Measure |
BPaMZ
n=21 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 26 Weeks
n=21 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 44 Weeks
n=20 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
BPaMZ 78 Weeks
n=18 Participants
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|---|---|---|
|
Inhibin B
|
122 pg/mL
Interval 72.0 to 155.0
|
137 pg/mL
Interval 105.0 to 189.0
|
162.5 pg/mL
Interval 96.0 to 194.5
|
172 pg/mL
Interval 110.0 to 188.0
|
Adverse Events
BPaMZ
Serious events: 2 serious events
Other events: 21 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
BPaMZ
n=26 participants at risk
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|
|
Infections and infestations
infective exacerbation of bronchiectasis
|
3.8%
1/26 • Number of events 1 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
hepatic enzyme increased
|
3.8%
1/26 • Number of events 1 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
Other adverse events
| Measure |
BPaMZ
n=26 participants at risk
Participants will receive bedaquiline 200 mg once daily for 8 weeks then 100 mg once daily for 18 weeks together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg once daily (BPaMZ) for 26 weeks.
Pretomanid: pretomanid 200 mg (once daily) for 26 weeks (with meal)
Bedaquiline: bedaquiline 200 mg (once daily) for 8 weeks (with meal), then bedaquiline 100mg (once daily) for 18 weeks (with meal)
moxifloxacin: moxifloxacin 400 mg (once daily) for 26 weeks (with meal)
pyrazinamide: pyrazinamide 1500 mg (once daily) for 26 weeks (with meal)
|
|---|---|
|
Gastrointestinal disorders
constipation
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Gastrointestinal disorders
diarrhoea
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Gastrointestinal disorders
gastrooesophageal reflux disease
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Gastrointestinal disorders
haemorrhoids
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Gastrointestinal disorders
nausea
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Hepatobiliary disorders
hypertransaminasaemia
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Infections and infestations
conjunctivitis
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Infections and infestations
lower respiratory infection
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Infections and infestations
pneumonia
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Infections and infestations
upper respiratory tract infection
|
15.4%
4/26 • Number of events 4 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
aspartate aminotransferase increased
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
blood potassium decreased
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
blood uric acid increased
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
gamma-glutamyltransferase increased
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Investigations
hepatic enzyme increased
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Metabolism and nutrition disorders
decreased appetite
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Metabolism and nutrition disorders
hyperuricaemia
|
15.4%
4/26 • Number of events 4 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Metabolism and nutrition disorders
hyponatraemia
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Musculoskeletal and connective tissue disorders
arthralgia
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Musculoskeletal and connective tissue disorders
myalgia
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Nervous system disorders
dizziness
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Respiratory, thoracic and mediastinal disorders
cough
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Respiratory, thoracic and mediastinal disorders
haemoptysis
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Respiratory, thoracic and mediastinal disorders
pleural effusion
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Respiratory, thoracic and mediastinal disorders
pleuritic pain
|
19.2%
5/26 • Number of events 5 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Skin and subcutaneous tissue disorders
dry skin
|
7.7%
2/26 • Number of events 2 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
|
Skin and subcutaneous tissue disorders
pruritus
|
11.5%
3/26 • Number of events 3 • All adverse events (including Serious adverse events) listed in result's are treatment emergent; defined in this trial AEs which started or worsened on or after the first administration of BPaMZ up to and including last date scheduled study drug (up to 26 weeks) was administered plus 2 weeks following last treatment dose. .
|
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