Evaluating the Safety, Tolerability, and Pharmacokinetics... | NCT02583048

NCT02583048

ID	Type	Description	Link
12005	Registry Identifier	DAIDS-ES Registry

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Arm 1: Bedaquiline	Experimental	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. Participants also received Multidrug Background Treatment (MBT) for TB. For HIV-positive participants only, one 50 mg tablet of Dolutegravir was taken in combination with two NRTIs until study completion.	Drug: Bedaquiline Drug: Dolutegravir Drug: Multidrug Background Treatment (MBT) for TB
Arm 2: Delamanid	Experimental	Participants received 100 mg of delamanid twice a day for 24 weeks. Participants also received Multidrug Background Treatment (MBT) for TB. For HIV-positive participants only, one 50 mg tablet of Dolutegravir was taken in combination with two NRTIs until study completion.	Drug: Delamanid Drug: Dolutegravir Drug: Multidrug Background Treatment (MBT) for TB
Arm 3: Bedaquiline and Delamanid	Experimental	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. Participants also received Multidrug Background Treatment (MBT) for TB. For HIV-positive participants only, one 50 mg tablet of Dolutegravir was taken in combination with two NRTIs until study completion.	Drug: Bedaquiline Drug: Delamanid Drug: Dolutegravir Drug: Multidrug Background Treatment (MBT) for TB

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Bedaquiline	Drug	Four 100 mg tablets (400 mg) orally once a day for 2 weeks, followed by two 100 mg tablets (200 mg) orally three times a week for 22 weeks.	Arm 1: Bedaquiline

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Mean Change From Baseline in QTcF	Mean change from baseline in QTcF (ie, QTcF prolongation) in milliseconds (ms), where baseline QTcF was represented by QTcF durations measured at week 0, and post-baseline QTcF was represented by QTcF durations measured at weeks 8 through 24 (pooled). QTcF calculated as average of 1-3 available QTcF values per visit.	Baseline and at weeks 8, 10, 12, 14, 16, 18, 20, 22 and 24
Post-Baseline QTcF	Baseline and post-baseline absolute QTcF in milliseconds (ms) estimated using an ANOVA model, where baseline QTcF was represented by QTcF durations measured at week 0, and post-baseline QTcF was represented by QTcF durations measured at weeks 8 through 24 (pooled). QTcF calculated as average of 1-3 available QTcF values per visit. Interim analysis conducted when week 24 QT data was available for ≥12 participants stipulated 99.9% confidence interval; original coverage of 95% was widened to 95.1%.	Baseline and at weeks 8, 10, 12, 14, 16, 18, 20, 22, and 24.

Secondary Outcomes

Measure	Description	Time Frame
Percentage of Participants With an Occurrence of QTcF Greater Than 500 Milliseconds (ms)	Participants who experienced QTcF greater than 500 ms at least once at any time from week 2 to 24. QTcF calculated as average of 1-3 available QTcF values per visit.	At weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Documented pulmonary infection due to strains of MTB with (a) resistance to isoniazid (INH) and rifampin (RIF) (MDR-TB) or (b) resistance to RIF but not INH (RR-TB) from a sputum sample collected within 60 days prior to entry.
Laboratory confirmation of infection with an MTB strain that is susceptible to fluoroquinolones and aminoglycosides within 60 days prior to entry.
HIV-1 infection status documented as either absent or present, as defined below:
- Absence of HIV-1 infection, within 60 days prior to entry. OR
- HIV-1 infection
For HIV-positive participants only: CD4+ count greater than or equal to 100 cells/mm^3 within 60 days prior to entry.
For HIV-positive participants only: For participants on ART for greater than or equal to 6 months and have an HIV-1 viral load greater than 500 copies/mL within 60 days prior to entry, a HIV-1 genotype within 60 days prior to entry must have shown that at least one fully active NRTI was available to the participant within the country program.
For females of reproductive potential, a negative serum pregnancy test within 48 hours prior to entry
All participants of reproductive potential who are participating in sexual activity that could lead to pregnancy must have agreed to use one method of birth control while receiving TB study medications and for 6 months after stopping TB study medications.
Participants who were not of reproductive potential were eligible without requiring the use of contraceptives.
For HIV-positive female participants of reproductive potential, the use of contraceptives was required for the full duration of time the participant was taking dolutegravir (ie, through study completion at week 128).
Chest x-ray performed within 60 days prior to entry to classify participant as having cavitary or non-cavitary disease
Documentation of Karnofsky performance score greater than or equal to 50 within 14 days prior to study entry
Ability and willingness of participant or legally authorized representative to provide informed consent
Willingness to be hospitalized for the required inpatient component of the study
Taking MBT for a minimum of 7 days within the 10 days prior to entry

Exclusion Criteria:

History of clinically relevant, currently active or underlying gastrointestinal, hepatic, cardiovascular, nervous system, psychiatric, metabolic (e.g., untreated hypothyroidism), renal, respiratory (other than due to TB), inflammatory, neoplastic, skin, immunological or infectious disease, which is not stable and controlled, that in the opinion of the investigator would preclude safe participation in the trial
Current clinically relevant extrapulmonary TB, in the opinion of the site investigator, including but not limited to central nervous system (CNS) TB or TB osteoarthritis
Previous treatment for MDR- or RR-TB, other than for the qualifying episode, at any time in the past
Receipt of BDQ or DLM at any time in the past
Breastfeeding
QTcF interval greater than 450 ms within 72 hours prior to entry
Clinically significant ECG abnormality in the opinion of the site investigator within 60 days prior to entry, including but not limited to second or third degree atrioventricular (AV) block, prolongation of the QRS complex over 120 ms (in both male and female participants), or clinically important arrhythmia
Current clinically relevant cardiovascular disorder in the opinion of the site investigator, including but not limited to heart failure, coronary heart disease, arrhythmia, or tachyarrhythmia
Known family history of Long QT Syndrome in a first-degree relative (i.e., parent, offspring, or sibling)
Requirement or expected requirement for protease inhibitors (PIs), efavirenz (EFV), or any other medication that is a moderate to strong inhibitor or inducer of CYP3A and CYP3A4 over the 24 weeks of study treatment. NOTE: Participants taking a PI or EFV can be switched to a treatment that is allowed in the study, but the PI must be stopped at least 2 days prior to starting study MDR- or RR-TB drugs and EFV must be stopped at least 7 days prior to starting study MDR- or RR-TB drugs.
Requirement or expected requirement for a medication that significantly prolongs QTc, including but not limited to moxifloxacin (levofloxacin is acceptable), from 72 hours prior to study entry through 4 weeks after discontinuation of study treatment (week 28)
Requirement or expected requirement of clofazimine, from 7 days prior to study entry through week 24 (discontinuation of study treatment).
For individuals receiving the WHO short course regimen that contains clofazimine, receipt of more than 21 cumulative days of clofazimine at any time prior to, or at the time of, study entry.
Known allergy/sensitivity or any hypersensitivity to components of study TB drugs or their formulation or to the nitroimidazole class of antibiotics
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements
Any of the following laboratory abnormalities within 14 days prior to entry:
1. Serum creatinine greater than 1.4 x upper limit of normal (ULN)
2. Lipase greater than 1.6 x ULN
3. Alanine aminotransferase (ALT) greater than 2.5 x ULN
4. Total bilirubin greater than 1.6 x ULN
5. Potassium less than 3.4 or greater than 5.6 mmol/L; magnesium less than 0.59 mmol/L; calcium less than 1.75 mmol/L
Known current hepatitis B or C infection, current treatment for hepatitis B or hepatitis C infection, or positive for hepatitis B surface antigen or hepatitis C antibodies within 60 days prior to entry
Among participants with HIV infection, in whom use of dolutegravir (DTG) is anticipated, any of the following:
1. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, esophageal varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones)
2. History or presence of allergy to DTG or its components
3. Severe hepatic impairment (Class C) as determined by Child-Pugh classification
4. Previous use of raltegravir
Documentation of any new and/or unstable AIDS-defining illness (other than TB) as defined by the CDC within 60 days prior to entry
Acute or serious illness (other than TB) requiring systemic treatment and/or hospitalization within 60 days prior to entry

Contacts/Locations Module

Name	Affiliation	Role
Kelly Dooley, MD, PhD	Johns Hopkins Adult AIDS CRS	Study Chair
Gary Maartens, MBChB, MMed	University of Cape Town	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Barranco CRS		Lima		15063	Peru
Task Applied Science (TASK) CRS

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
35668346	Derived	Tanneau L, Karlsson MO, Diacon AH, Shenje J, De Los Rios J, Wiesner L, Upton CM, Dooley KE, Maartens G, Svensson EM. Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline. Clin Pharmacokinet. 2022 Aug;61(8):1177-1185. doi: 10.1007/s40262-022-01133-2. Epub 2022 Jun 7.
33587897

Label	URL
Location of DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, November 2014	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: One 50 mg tablet of Dolutegravir was taken orally once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jun 26, 2018	Jan 3, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Arm 3: Bedaquiline and Delamanid

All randomized participants.

Arm/Group Information

ID	Title	Description
BG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: One 50 mg tablet of Dolutegravir was taken orally once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
BG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: One 50 mg tablet of Dolutegravir was taken orally once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
BG002	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: One 50 mg tablet of Dolutegravir was taken orally once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
BG003	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Median

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00034.5(20 to 58) BG00132(18 to 73) BG00234(18 to 55) BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0006 BG0017 BG002

Race/Ethnicity, Customized

Count of Participants

Participants

Title

Denominators

Categories

White

Title	Measurements
	BG0000 BG0011 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

South Africa

Title	Measurements
	BG00027 BG00126 BG002

Baseline QTcF

Median

Full Range

milliseconds

Title

Denominators

Categories

Title	Measurements
	BG000394.3(360.7 to 461.0) BG001406.2(364.3 to 445.0) BG002

HIV-1 Positive

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
	BG00010 BG00111 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Mean Change From Baseline in QTcF

Mean change from baseline in QTcF (ie, QTcF prolongation) in milliseconds (ms), where baseline QTcF was represented by QTcF durations measured at week 0, and post-baseline QTcF was represented by QTcF durations measured at weeks 8 through 24 (pooled). QTcF calculated as average of 1-3 available QTcF values per visit.

Participants with a baseline QTcF measurement, and at least one post-baseline QTcF measurement from a visit conducted at week 8 through 24, prior to permanent discontinuation of study Tuberculosis (TB) drug and without a temporary discontinuation of study TB drug of 7 or more days immediately preceding the measurement.

Posted

Mean

95.1% Confidence Interval

milliseconds (ms)

Baseline and at weeks 8, 10, 12, 14, 16, 18, 20, 22 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG002	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Units	Counts
Participants	OG00026 OG00125 OG00224

Title

Denominators

Categories

Title	Measurements
	OG00012.3(7.8 to 16.7) OG0018.6(4.0 to 13.1) OG00220.7(16.1 to 25.3)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG002						Mean Difference (Net)	8.4			2-Sided	95.1	2.0	14.8			Arm 3 minus Arm 1 difference in change from baseline estimated from ANOVA model. Interim analysis conducted when week 24 QT data was available for ≥12 participants stipulated 99.9% confidence interval; original coverage of 95% was widened to 95.1%.		Superiority
OG001 OG002

Primary

Post-Baseline QTcF

Baseline and post-baseline absolute QTcF in milliseconds (ms) estimated using an ANOVA model, where baseline QTcF was represented by QTcF durations measured at week 0, and post-baseline QTcF was represented by QTcF durations measured at weeks 8 through 24 (pooled). QTcF calculated as average of 1-3 available QTcF values per visit. Interim analysis conducted when week 24 QT data was available for ≥12 participants stipulated 99.9% confidence interval; original coverage of 95% was widened to 95.1%.

Posted

Least Squares Mean

95.1% Confidence Interval

milliseconds (ms)

Baseline and at weeks 8, 10, 12, 14, 16, 18, 20, 22, and 24.

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid

Secondary

Percentage of Participants With an Occurrence of QTcF Greater Than 500 Milliseconds (ms)

Participants who experienced QTcF greater than 500 ms at least once at any time from week 2 to 24. QTcF calculated as average of 1-3 available QTcF values per visit.

Participants who took at least one dose of study TB treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

At weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG002

Secondary

Percentage of Participants With an Increase in QTcF From Baseline of Greater Than 60 Milliseconds (ms)

Participants who experienced QTcF increase from baseline greater than 60 ms at least once at any time from week 2 to 24. QTcF calculated as average of 1-3 available QTcF values per visit.

Participants who took at least one dose of study TB treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline and at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

Changes in QTcF From Baseline

Change from baseline in QTcF, calculated as the difference between each post-baseline week and week 0. (QTcF calculated as average of 1-3 available QTcF values per visit.)

Participants with baseline and at least one post baseline QTcF collected at a scheduled visit while taking study TB drug(s).

Posted

Median

Full Range

milliseconds (ms)

Baseline and at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24 and 28.

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG002

Secondary

Percentage of Participants With an Occurrence of QTcF >480 and ≤500 Milliseconds (ms)

Participants who experienced QTcF >480 and ≤500 ms at least once at any time from week 2 to 24. QTcF calculated as average of 1-3 available QTcF values per visit.

Participants who took at least one dose of study TB drug(s).

Posted

Number

95% Confidence Interval

Percentage of participants

At weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG002

Secondary

Percentage of Participants With an Occurrence of QTcF Increase From Baseline of >30 and ≤60 Milliseconds (ms)

Participants who experienced QTcF increase from baseline of >30 and ≤60 ms at least once at any time from week 2 to 24. QTcF calculated as average of 1-3 available QTcF values per visit.

Participants who took at least one dose of study treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

Baseline and at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

BDQ PK Parameter Minimum Plasma Concentration (Cmin) Determined Based on BDQ Levels From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the BDQ PK parameter Cmin obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). Cmin defines minimum concentration observed over the first 22 hours of the BDQ dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive BDQ PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

BDQ PK Parameter Maxmum Plasma Concentration (Cmax) Determined Based on BDQ Levels From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the BDQ PK parameter Cmax obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). Cmax defines maximum concentration observed over the first 22 hours of the BDQ dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive BDQ PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

BDQ PK Parameter Area Under the Concentration Time Curve (AUC 0-22h) Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the BDQ PK parameter AUC 0-22h obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). AUC 0-22h defines area under the concentration-time curve over the period of 22 hours post-dose.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng*h/mL

Intensive BDQ PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at Weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

N-monodesmethyl Metabolite of BDQ PK Parameter Cmin Determined Based on BDQ Metabolite Levels From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the N-monodesmethyl Metabolite of BDQ PK parameter Cmin obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). Cmin defines minimum concentration observed over the first 22 hours of the BDQ dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive BDQ Metabolite PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

N-monodesmethyl Metabolite of BDQ PK Parameter Cmax Determined Based on BDQ Metabolite Levels From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the BDQ Metabolite N-monodesmethyl BDQ PK parameter Cmax obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). Cmax defines maximum concentration observed over the first 22 hours of the BDQ dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive BDQ Metabolite PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

N-monodesmethyl Metabolite of BDQ PK Parameter AUC 0-22h Calculated Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arms 1 and 3

This evaluates the effect of DLM on the N-monodesmethyl Metabolite of BDQ PK parameter AUC 0-22h obtained from participants enrolled in Arms 1 and 3 (without and with co-administration of DLM). AUC 0-22h defines area under the concentration-time curve over the period of 22 hours post-dose.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng*h/mL

Intensive BDQ PK samples at pre-dose, 5h, 7h, 10h and 22h post-dose at Weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM PK Parameter Cmin Determined Based on DLM Levels From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM PK parameter Cmin obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). Cmin defines minimum concentration observed over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM PK Parameter Cmax Determined Based on DLM Levels From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM PK parameter Cmax obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). Cmax defines maximum concentration observed over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM PK Area Under the Concentration Time Curve (AUC 0-11h) Determined Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM PK parameter AUC 0-11h obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). AUC 0-11h defines area under the concentration-time curve over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng*h/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM Metabolite DM6705 PK Parameter Cmin Determined Based on DLM Metabolite Levels From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM Metabolite DM6705 PK parameter Cmin obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). Cmin defines minimum concentration observed over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM Metabolite DM6705 PK Parameter Cmax Determined Based on DLM Metabolite Levels From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM Metabolite DM6705 PK parameter Cmax obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). Cmax defines maximum concentration observed over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

DLM Metabolite DM6705 PK AUC 0-11h Determined Based on Intensive PK Samples Obtained From Individual Participants Enrolled in Arms 2 and 3

This evaluates the effect of BDQ on the DLM Metabolite DM6705 PK parameter AUC 0-11h obtained from participants enrolled in Arms 2 and 3 (without and with co-administration of BDQ). AUC 0-11h defines area under the concentration-time curve over the first 11 hours of the DLM dosing interval.

Participants who took at least one dose of study treatment, and were taking study drug at the time of the PK visit.

Posted

Mean

Standard Deviation

ng*h/mL

Intensive DLM PK samples at pre-dose, 4h, 8h, and 11h post-dose at weeks 2, 8 and 24

ID	Title	Description
OG000	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

Percentage of Participants With an Occurrence of Grade 3 or Higher Adverse Event

Participants with an occurrence of an adverse event (laboratory value, sign/symptom, diagnosis) of grade 3 or 4. Severity grading based on DAIDS AE Grading Table Version 2.0. Participants were counted once at the highest grade (grade 3 or grade 4).

Participants who took at least one dose of study TB treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

From initiation of study TB treatment (week 0) to week 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Secondary

Percentage of Participants Who Discontinued Study TB Drug(s) For Any Reason

Percentage of participants who discontinued study TB drug(s) for any reason

Participants who took at least one dose of study TB treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

From initiation of study TB treatment (week 0) to week 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG002	Arm 3: Bedaquiline and Delamanid

Secondary

Percentage of Participants Who Died

Among participants who took at least one dose of study TB treatment, percentage of participants who died on or before week 24. Note that the all-cause mortality includes deaths that occurred at any time during treatment or follow-up through week 128.

Participants who took at least one dose of study TB treatment.

Posted

Number

95% Confidence Interval

Percentage of participants

From initiation of study TB treatment (week 0) to week 24

ID	Title	Description
OG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).
OG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Arm 1: Bedaquiline	Participants received 400 mg of bedaquiline once a day for 2 weeks followed by 200 mg of bedaquiline three times a week for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).	0	28	2	28	21	28
EG001	Arm 2: Delamanid	Participants received 100 mg of delamanid twice a day for 24 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).	1	27	3	27	16	27
EG002	Arm 3: Bedaquiline and Delamanid	Participants received 400 mg of bedaquiline once a day and 100 mg of delamanid twice a day for 2 weeks. They then received 200 mg of bedaquiline three times a week and 100 mg of delamanid twice a day for 22 weeks. For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.) Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).	0	27	8	27	21	27

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pancreatitis	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected27 at risk EG0020 affected27 at risk
Drug-induced liver injury	Hepatobiliary disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Hypersensitivity	Immune system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Stab wound	Injury, poisoning and procedural complications	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected27 at risk EG0024 affected27 at risk
Electrocardiogram QT prolonged	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected27 at risk EG0020 affected27 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected27 at risk EG0020 affected27 at risk
Focal dyscognitive seizures	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Generalised tonic-clonic seizure	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Seizure	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Major depression	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected27 at risk EG0020 affected27 at risk
Substance-induced psychotic disorder	Psychiatric disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Deafness	Ear and labyrinth disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected27 at risk EG0026 affected27 at risk
Deafness neurosensory	Ear and labyrinth disorders	MedDRA 24.1	Systematic Assessment	EG0008 affected28 at risk EG0014 affected27 at risk EG0024 affected27 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Conjunctivitis allergic	Eye disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected27 at risk EG0021 affected27 at risk
Optic neuropathy	Eye disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected27 at risk EG0021 affected27 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected27 at risk EG0022 affected27 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0013 affected27 at risk EG0021 affected27 at risk
Nausea	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected27 at risk EG0023 affected27 at risk
Vomiting	Gastrointestinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Injection site reaction	General disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Acute sinusitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0013 affected27 at risk EG0021 affected27 at risk
Oral candidiasis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0016 affected27 at risk EG0021 affected27 at risk
Oral herpes	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Pharyngitis	Infections and infestations	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0015 affected27 at risk EG0022 affected27 at risk
Alanine aminotransferase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Blood albumin decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Blood glucose decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0011 affected27 at risk EG0022 affected27 at risk
Blood uric acid increased	Investigations	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0011 affected27 at risk EG0020 affected27 at risk
Haemoglobin decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Weight decreased	Investigations	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0020 affected27 at risk
Costochondritis	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 24.1	Systematic Assessment	EG0004 affected28 at risk EG0010 affected27 at risk EG0021 affected27 at risk
Dizziness	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Headache	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected27 at risk EG0020 affected27 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected27 at risk EG0020 affected27 at risk
Neuropathy peripheral	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0006 affected28 at risk EG0012 affected27 at risk EG0023 affected27 at risk
Paraesthesia	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0004 affected28 at risk EG0011 affected27 at risk EG0022 affected27 at risk
Seizure	Nervous system disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0023 affected27 at risk
Chronic obstructive pulmonary disease	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0000 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0013 affected27 at risk EG0022 affected27 at risk
Rhinitis allergic	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0010 affected27 at risk EG0022 affected27 at risk
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 24.1	Systematic Assessment	EG0004 affected28 at risk EG0012 affected27 at risk EG0021 affected27 at risk
Acne	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0008 affected28 at risk EG0016 affected27 at risk EG0028 affected27 at risk
Drug eruption	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0011 affected27 at risk EG0022 affected27 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0003 affected28 at risk EG0012 affected27 at risk EG0024 affected27 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 24.1	Systematic Assessment	EG0001 affected28 at risk EG0012 affected27 at risk EG0021 affected27 at risk
Hypertension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0011 affected27 at risk EG0021 affected27 at risk
Orthostatic hypotension	Vascular disorders	MedDRA 24.1	Systematic Assessment	EG0002 affected28 at risk EG0010 affected27 at risk EG0020 affected27 at risk

Point of Contact

Title	Organization	Phone	Extension	Email
ACTG Clinicaltrials.gov Coordinator	ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company.	(301) 628-3348		ACTGCT.gov@fstrf.org

ID	Term
D014376	Tuberculosis
D015658	HIV Infections

Ancestor Terms

ID	Term
D009164	Mycobacterium Infections
D000193	Actinomycetales Infections
D016908	Gram-Positive Bacterial Infections
D001424	Bacterial Infections
D001423	Bacterial Infections and Mycoses
D007239	Infections
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D015229	Sexually Transmitted Diseases, Viral
D012749	Sexually Transmitted Diseases
D016180	Lentivirus Infections
D012192	Retroviridae Infections
D012327	RNA Virus Infections
D014777	Virus Diseases
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D007153	Immunologic Deficiency Syndromes
D007154	Immune System Diseases

ID	Term
C493870	bedaquiline
C516022	OPC-67683
C562325	dolutegravir

BG003395.5(360.7 to 461.0)

Participants received 100 mg of delamanid twice a day for 24 weeks.

For HIV-positive participants only: dolutegravir was administered at a dose of one 50 mg tablet once daily, to be used in combination with two NRTIs until study completion. (NRTIs not provided by the study.)

Participants also took Multidrug Background Treatment (MBT) for TB (not provided by the study).

OG0018.70(-15.70 to 24.70)

OG00214.30(-8.70 to 50.30)

OG0019.30(-19.00 to 37.70)

OG00215.30(-11.00 to 33.70)

OG0017.00(-30.30 to 39.00)

OG00220.30(-14.00 to 47.30)

OG0017.80(-25.30 to 37.70)

OG00218.30(-15.00 to 58.30)

OG00110.30(-21.00 to 38.70)

OG00220.30(-20.30 to 50.30)

OG0015.30(-18.00 to 49.00)

OG00221.30(-19.00 to 51.00)

OG0017.35(-46.00 to 38.70)

OG00221.00(-22.70 to 62.70)

OG00111.70(-28.30 to 39.30)

OG00212.70(-26.70 to 66.30)

OG00113.65(-21.30 to 29.30)

OG00221.00(-18.30 to 70.00)

OG0019.00(-15.70 to 34.30)

OG00220.85(-19.30 to 75.00)

OG00113.00(-19.30 to 40.30)

OG00224.00(-19.00 to 46.30)

OG0016.00(-25.30 to 38.30)

OG00217.65(-16.00 to 55.70)