Trial Outcomes & Findings for Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients (NCT NCT03338621)

Last Updated: 2024-03-07

Results Overview

Culture negative status is achieved when a participant produces at least two negative culture results at different visits (at least 7 days apart) without an intervening positive culture result for M.tb.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

455 participants

Primary outcome timeframe

Days 0-56 (8 weeks)

Results posted on

2024-03-07

Participant Flow

Participant milestones

Participant milestones
Measure	Drug Sensitive-TB 4BPaMZ Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Sensitive-TB 2HRZE/4HR isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets Participant Dosage based on weight	Drug Resistant-TB 6BPaMZ Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Overall Study STARTED	150	153	152
Overall Study COMPLETED	121	134	117
Overall Study NOT COMPLETED	29	19	35

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Trial to Evaluate the Efficacy, Safety and Tolerability of BPaMZ in Drug-Sensitive (DS-TB) Adult Patients and Drug-Resistant (DR-TB) Adult Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Drug Sensitive-TB 4BPaMZ n=150 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Sensitive-TB 2HRZE/4HR n=153 Participants isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets Participant Dosage based on weight	Drug Resistant-TB 6BPaMZ n=152 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Total n=455 Participants Total of all reporting groups
Smoking Former	32 Participants n=5 Participants	40 Participants n=7 Participants	41 Participants n=5 Participants	113 Participants n=4 Participants
Alcohol Use Never	37 Participants n=5 Participants	42 Participants n=7 Participants	55 Participants n=5 Participants	134 Participants n=4 Participants
Age, Continuous	36.4 years n=5 Participants	36.3 years n=7 Participants	37.6 years n=5 Participants	36.7 years n=4 Participants
Sex: Female, Male Female	38 Participants n=5 Participants	35 Participants n=7 Participants	58 Participants n=5 Participants	131 Participants n=4 Participants
Sex: Female, Male Male	112 Participants n=5 Participants	118 Participants n=7 Participants	94 Participants n=5 Participants	324 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	8 Participants n=5 Participants	3 Participants n=7 Participants	13 Participants n=5 Participants	24 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	108 Participants n=5 Participants	119 Participants n=7 Participants	82 Participants n=5 Participants	309 Participants n=4 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	25 Participants n=7 Participants	31 Participants n=5 Participants	85 Participants n=4 Participants
Race (NIH/OMB) More than one race	5 Participants n=5 Participants	6 Participants n=7 Participants	26 Participants n=5 Participants	37 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Region of Enrollment Philippines	6 Participants n=5 Participants	2 Participants n=7 Participants	9 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Tanzania	52 Participants n=5 Participants	48 Participants n=7 Participants	7 Participants n=5 Participants	107 Participants n=4 Participants
Region of Enrollment Brazil	4 Participants n=5 Participants	3 Participants n=7 Participants	28 Participants n=5 Participants	35 Participants n=4 Participants
Region of Enrollment South Africa	56 Participants n=5 Participants	68 Participants n=7 Participants	72 Participants n=5 Participants	196 Participants n=4 Participants
Region of Enrollment Uganda	3 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants	17 Participants n=4 Participants
Region of Enrollment Malaysia	2 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants	7 Participants n=4 Participants
Region of Enrollment Georgia	23 Participants n=5 Participants	20 Participants n=7 Participants	9 Participants n=5 Participants	52 Participants n=4 Participants
Region of Enrollment Russia	4 Participants n=5 Participants	5 Participants n=7 Participants	15 Participants n=5 Participants	24 Participants n=4 Participants
Height	168.1 cm n=5 Participants	168.9 cm n=7 Participants	167.8 cm n=5 Participants	168.3 cm n=4 Participants
Weight	56.5 kg n=5 Participants	55.6 kg n=7 Participants	56.6 kg n=5 Participants	56.3 kg n=4 Participants
BMI	20.0 Kg/m^2 n=5 Participants	19.5 Kg/m^2 n=7 Participants	20.1 Kg/m^2 n=5 Participants	19.9 Kg/m^2 n=4 Participants
HIV Status Positive	25 Participants n=5 Participants	27 Participants n=7 Participants	35 Participants n=5 Participants	87 Participants n=4 Participants
HIV Status Negative	125 Participants n=5 Participants	126 Participants n=7 Participants	117 Participants n=5 Participants	368 Participants n=4 Participants
Smoking Never	59 Participants n=5 Participants	49 Participants n=7 Participants	72 Participants n=5 Participants	180 Participants n=4 Participants
Smoking Current	59 Participants n=5 Participants	64 Participants n=7 Participants	39 Participants n=5 Participants	162 Participants n=4 Participants
Alcohol Use Current	63 Participants n=5 Participants	69 Participants n=7 Participants	48 Participants n=5 Participants	180 Participants n=4 Participants
Alcohol Use Former	50 Participants n=5 Participants	42 Participants n=7 Participants	49 Participants n=5 Participants	141 Participants n=4 Participants
Previous Tuberculosis (TB) diagnoses Drug Sensitive (DS-TB)	150 participants n=5 Participants	153 participants n=7 Participants	33 participants n=5 Participants	336 participants n=4 Participants
Previous Tuberculosis (TB) diagnoses Mono-resistant TB	0 participants n=5 Participants	0 participants n=7 Participants	45 participants n=5 Participants	45 participants n=4 Participants
Previous Tuberculosis (TB) diagnoses Multi-drug Resistant (MDR-TB)	0 participants n=5 Participants	0 participants n=7 Participants	99 participants n=5 Participants	99 participants n=4 Participants
Previous Tuberculosis (TB) diagnoses Pre-extensively Resistant (Pre-XDR TB)	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Previous Tuberculosis (TB) diagnoses Extensively Resistant (XDR-TB)	0 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants	2 participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) No AFB seen	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) Scanty Positive	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) 1+	20 Participants n=5 Participants	28 Participants n=7 Participants	37 Participants n=5 Participants	85 Participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) 2+	49 Participants n=5 Participants	53 Participants n=7 Participants	47 Participants n=5 Participants	149 Participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) 3+	81 Participants n=5 Participants	72 Participants n=7 Participants	67 Participants n=5 Participants	220 Participants n=4 Participants
Screening smear microscopy for Acid Fast Bacilli (AFB) Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Time to positive at baseline	5.4 days n=5 Participants	5.8 days n=7 Participants	7.4 days n=5 Participants	6.2 days n=4 Participants
Chest x-ray at Screening Normal	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants	14 Participants n=4 Participants
Chest x-ray at Screening Abnormal	145 Participants n=5 Participants	151 Participants n=7 Participants	144 Participants n=5 Participants	440 Participants n=4 Participants
Chest x-ray at Screening Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Chest X-Ray Cavities at Screening None	31 Participants n=5 Participants	37 Participants n=7 Participants	31 Participants n=5 Participants	99 Participants n=4 Participants
Chest X-Ray Cavities at Screening Unilateral	75 Participants n=5 Participants	76 Participants n=7 Participants	70 Participants n=5 Participants	221 Participants n=4 Participants
Chest X-Ray Cavities at Screening Bilateral	44 Participants n=5 Participants	40 Participants n=7 Participants	50 Participants n=5 Participants	134 Participants n=4 Participants
Chest X-Ray Cavities at Screening Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Days 0-56 (8 weeks)

Population: Limited to Drug Sensitive TB groups. Participants were considered unassessable and therefore excluded from the Modified Intent to Treat (MITT) population if they were late exclusion or if they did not have culture confirmation of M.tb at baseline.

Outcome measures

Outcome measures
Measure	Drug Sensitive-TB 2HRZE/4HR n=148 Participants isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets Participant Dosage based on weight	Drug Sensitive-TB 4BPaMZ n=145 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Resistant-TB 6BPaMZ Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Number of Participants With Culture Negative Status by 8 Weeks	70 Participants	122 Participants	—

SECONDARY outcome

Timeframe: 52 weeks after start of therapy

Population: TB Specific Modified Intent to Treat (TB-MITT) population participants were unassessable and excluded if they were a late exclusion, became pregnant and stopped treatment, had suspected or confirmed COVID-19 and stopped treatment, died during treatment from violent or accidental cause, died during follow-up with no evidence of TB, reinfected with a different strain of TB, had contaminated or missing sputum samples at the endpoint visit (and able to produce sputum).

Unfavorable 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 lost to follow up or withdrawn from the study before end of treatment

Outcome measures

Outcome measures
Measure	Drug Sensitive-TB 2HRZE/4HR n=144 Participants isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets Participant Dosage based on weight	Drug Sensitive-TB 4BPaMZ n=144 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Resistant-TB 6BPaMZ n=133 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months) Unfavorable	24 Participants	10 Participants	22 Participants
Number of Participants With Bacteriologic Failure or Relapse or Clinical Failure (Unfavorables) at 52 Weeks From Start of Therapy (12 Months) Favorable	120 Participants	134 Participants	111 Participants

SECONDARY outcome

Timeframe: During treatment (17 or 26 weeks)

Population: Participants were unassessable and excluded from the Modified Intent to Treat (MITT) population if they were a late exclusions.

Culture conversion is a diagnostic criteria indicating the point at which samples taken from a patient infected with a tuberculosis can no longer produce tuberculosis cell cultures, that point is considered culture negativity

Outcome measures

Outcome measures
Measure	Drug Sensitive-TB 2HRZE/4HR n=145 Participants isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets Participant Dosage based on weight	Drug Sensitive-TB 4BPaMZ n=148 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Resistant-TB 6BPaMZ n=133 Participants Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Time to Culture Negative Status	6 weeks Interval 4.0 to 8.0	11 weeks Interval 6.0 to 12.0	5 weeks Interval 3.0 to 7.0

Adverse Events

Drug Sensitive-TB BPaMZ

Serious events: 17 serious events

Other events: 139 other events

Deaths: 3 deaths

Drug Sensitive-TB 2HRZE/4HR

Serious events: 7 serious events

Other events: 144 other events

Deaths: 2 deaths

Drug Resistant-TB BPaMZ

Serious events: 16 serious events

Other events: 142 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Morounfolu Olugbosi

TB Alliance

Phone: 1 212 227 7540

Email: [email protected]

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

Serious adverse events
Measure	Drug Sensitive-TB BPaMZ n=150 participants at risk Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Sensitive-TB 2HRZE/4HR n=153 participants at risk isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets	Drug Resistant-TB BPaMZ n=149 participants at risk Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Blood and lymphatic system disorders Anaemia	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Blood and lymphatic system disorders Polycythaemia	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Cardiac disorders Cardiac Failure Congestive	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.65% 1/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Cardiac disorders Cor Pulmonae	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
General disorders Pyrexia	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Hepatobiliary disorders Cholecystitis Acute	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Hepatobiliary disorders Drug-Induced Liver Injury	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Hepatobiliary disorders Hepatotoxicity	5.3% 8/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.65% 1/153 • 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 study drug up to and including 14 days after the last study drug administration.	2.7% 4/149 • 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 study drug up to and including 14 days after the last study drug administration.
Immune system disorders Hypersensitivity	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations COVID-19	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Psoas Abscess	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.65% 1/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Sepsis	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Tuberculosis	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Electrocardiogram ST Segment Elevation	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Hepatic Enzyme Increased	1.3% 2/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Transaminases Increased	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	2.0% 3/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hypokalaemia	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Musculoskeletal and connective tissue disorders Musculoskeletal Chest Pain	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Nervous system disorders Post-Traumatic Epilepsy	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.65% 1/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Nervous system disorders Syncope	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Pregnancy, puerperium and perinatal conditions Abortion Spontaneous	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Respiratory, thoracic and mediastinal disorders Plueral Effusion	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Social circumstances Physical Assault	0.00% 0/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Vascular disorders Embolism	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.

Other adverse events
Measure	Drug Sensitive-TB BPaMZ n=150 participants at risk Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 9 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 17 weeks (Total treatment duration 4 months Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets	Drug Sensitive-TB 2HRZE/4HR n=153 participants at risk isoniazid 75 mg + rifampicin 150 mg + pyrazinamide 400 mg + ethambutol 275 mg (HRZE) combination tablets for 8 weeks AND isoniazid 75 mg + rifampicin 150 mg (HR) combination tablets for Weeks 9 to 26 HRZE: isoniazid 75 mg plus rifampicin 150 mg plus pyrazinamide 400 mg plus ethambutol 275 mg combination tablets HR: isoniazid 75 mg plus rifampicin 150 mg combination tablets	Drug Resistant-TB BPaMZ n=149 participants at risk Bedaquiline 200 mg daily for 8 weeks then 100 mg daily for 18 weeks, together with pretomanid 200 mg + moxifloxacin 400 mg + pyrazinamide 1500 mg daily for 26 weeks (Total treatment duration 6 months) Pretomanid: 200 mg tablets Bedaquiline: 100 mg tablets Moxifloxacin: 400 mg tablets Pyrazinamide: 500 mg tablets
Blood and lymphatic system disorders Anemia	6.0% 9/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.9% 9/153 • 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 study drug up to and including 14 days after the last study drug administration.	4.7% 7/149 • 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 study drug up to and including 14 days after the last study drug administration.
Gastrointestinal disorders Diarrhoea	7.3% 11/150 • 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 study drug up to and including 14 days after the last study drug administration.	3.3% 5/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.1% 18/149 • 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 study drug up to and including 14 days after the last study drug administration.
Gastrointestinal disorders Gastritis	8.0% 12/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	8.1% 12/149 • 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 study drug up to and including 14 days after the last study drug administration.
Gastrointestinal disorders Nausea	14.0% 21/150 • 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 study drug up to and including 14 days after the last study drug administration.	3.3% 5/153 • 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 study drug up to and including 14 days after the last study drug administration.	14.8% 22/149 • 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 study drug up to and including 14 days after the last study drug administration.
Gastrointestinal disorders Vomiting	7.3% 11/150 • 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 study drug up to and including 14 days after the last study drug administration.	4.6% 7/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.1% 18/149 • 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 study drug up to and including 14 days after the last study drug administration.
General disorders Pyrexia	6.0% 9/150 • 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 study drug up to and including 14 days after the last study drug administration.	2.6% 4/153 • 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 study drug up to and including 14 days after the last study drug administration.	2.0% 3/149 • 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 study drug up to and including 14 days after the last study drug administration.
Hepatobiliary disorders Hepatotoxicity	6.7% 10/150 • 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 study drug up to and including 14 days after the last study drug administration.	2.0% 3/153 • 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 study drug up to and including 14 days after the last study drug administration.	4.7% 7/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Conjunctivitis	2.0% 3/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	6.0% 9/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Upper Respiratory Tract Infection	2.0% 3/150 • 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 study drug up to and including 14 days after the last study drug administration.	7.8% 12/153 • 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 study drug up to and including 14 days after the last study drug administration.	6.7% 10/149 • 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 study drug up to and including 14 days after the last study drug administration.
Infections and infestations Urinary Tract Infection	6.7% 10/150 • 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 study drug up to and including 14 days after the last study drug administration.	9.2% 14/153 • 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 study drug up to and including 14 days after the last study drug administration.	3.4% 5/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Alanine Aminotransferase Increased	9.3% 14/150 • 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 study drug up to and including 14 days after the last study drug administration.	6.5% 10/153 • 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 study drug up to and including 14 days after the last study drug administration.	5.4% 8/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Aspartate Aminotransferase Increased	6.7% 10/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.9% 9/153 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Blood Alkaline Phosphatase Increased	3.3% 5/150 • 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 study drug up to and including 14 days after the last study drug administration.	7.2% 11/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Hepatic Enzyme Increased	12.0% 18/150 • 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 study drug up to and including 14 days after the last study drug administration.	9.2% 14/153 • 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 study drug up to and including 14 days after the last study drug administration.	7.4% 11/149 • 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 study drug up to and including 14 days after the last study drug administration.
Investigations Lipase Increased	4.0% 6/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.2% 8/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Decreased Appetite	4.0% 6/150 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/153 • 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 study drug up to and including 14 days after the last study drug administration.	7.4% 11/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hyperglycaemia	2.0% 3/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.2% 8/153 • 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 study drug up to and including 14 days after the last study drug administration.	0.67% 1/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hyperkalaemia	15.3% 23/150 • 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 study drug up to and including 14 days after the last study drug administration.	16.3% 25/153 • 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 study drug up to and including 14 days after the last study drug administration.	2.0% 3/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hyperuricaemia	48.7% 73/150 • 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 study drug up to and including 14 days after the last study drug administration.	45.1% 69/153 • 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 study drug up to and including 14 days after the last study drug administration.	28.9% 43/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hypokalaemia	6.0% 9/150 • 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 study drug up to and including 14 days after the last study drug administration.	0.00% 0/153 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/149 • 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 study drug up to and including 14 days after the last study drug administration.
Metabolism and nutrition disorders Hyponatraemia	4.7% 7/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.2% 8/153 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/149 • 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 study drug up to and including 14 days after the last study drug administration.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 30/150 • 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 study drug up to and including 14 days after the last study drug administration.	15.7% 24/153 • 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 study drug up to and including 14 days after the last study drug administration.	22.8% 34/149 • 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 study drug up to and including 14 days after the last study drug administration.
Musculoskeletal and connective tissue disorders Back Pain	2.7% 4/150 • 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 study drug up to and including 14 days after the last study drug administration.	5.9% 9/153 • 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 study drug up to and including 14 days after the last study drug administration.	2.0% 3/149 • 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 study drug up to and including 14 days after the last study drug administration.
Nervous system disorders Dizziness	4.7% 7/150 • 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 study drug up to and including 14 days after the last study drug administration.	2.6% 4/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.1% 18/149 • 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 study drug up to and including 14 days after the last study drug administration.
Nervous system disorders Headache	6.7% 10/150 • 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 study drug up to and including 14 days after the last study drug administration.	9.2% 14/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.1% 18/149 • 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 study drug up to and including 14 days after the last study drug administration.
Nervous system disorders Neuropathy Peripheral	3.3% 5/150 • 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 study drug up to and including 14 days after the last study drug administration.	7.2% 11/153 • 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 study drug up to and including 14 days after the last study drug administration.	4.7% 7/149 • 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 study drug up to and including 14 days after the last study drug administration.
Respiratory, thoracic and mediastinal disorders Cough	0.67% 1/150 • 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 study drug up to and including 14 days after the last study drug administration.	3.3% 5/153 • 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 study drug up to and including 14 days after the last study drug administration.	5.4% 8/149 • 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 study drug up to and including 14 days after the last study drug administration.
Respiratory, thoracic and mediastinal disorders Dyspnoea	2.0% 3/150 • 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 study drug up to and including 14 days after the last study drug administration.	1.3% 2/153 • 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 study drug up to and including 14 days after the last study drug administration.	6.0% 9/149 • 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 study drug up to and including 14 days after the last study drug administration.
Respiratory, thoracic and mediastinal disorders Haemoptysis	2.7% 4/150 • 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 study drug up to and including 14 days after the last study drug administration.	9.2% 14/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.8% 19/149 • 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 study drug up to and including 14 days after the last study drug administration.
Skin and subcutaneous tissue disorders Pruritus	4.0% 6/150 • 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 study drug up to and including 14 days after the last study drug administration.	8.5% 13/153 • 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 study drug up to and including 14 days after the last study drug administration.	12.8% 19/149 • 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 study drug up to and including 14 days after the last study drug administration.