A Trial to Evaluate OPC 67683 in Participants With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)

A Multi Center, Randomized, Double-blind, Placebo-controlled Phase 2 Trial to Evaluate the Safety, Efficacy and Pharmacokinetics of Multiple Doses of OPC 67683 in Patients With Pulmonary Sputum Culture-Positive, Multidrug-resistant Tuberculosis

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00685360

Enrollment

481

Registered

2008-05-28

Start date

2008-05-08

Completion date

2010-06-11

Last updated

2021-12-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Tuberculosis, Pulmonary, Tuberculosis, Multidrug Resistant, Extensively Drug-Resistant Tuberculosis

Keywords

Tuberculosis, Pulmonary, Multidrug resistant, Antitubercular Agents, OPC 67683

Brief summary

This is a clinical trial to evaluate the safety and efficacy of OPC-67683 in the treatment of multidrug resistant tuberculosis (MDR TB) for 56 days. In addition to an optimized background regimen (OBR), participants will be randomized to receive: * 100 mg OPC-67683 twice daily (BID) * 200 mg OPC-67683 BID * Placebo BID After 56 days participants will complete their optimized background regimen (OBR).

Detailed description

This is a multi center, randomized, double-blinded, stratified, placebo-controlled clinical trial in three parallel groups. Participants will be randomized to one of the following three treatment groups: * OBR plus 100 mg OPC-67683 BID * OBR plus 200 mg OPC-67683 BID * OBR plus placebo BID The three treatment groups will comprise approximately 140 participants each (male or female). The trial will consist of the following periods: * Pre-treatment Period (Visits 1 to 3 \[Day -9 to Day -1\]) * Treatment Period (Visits 4 to 59 \[Days 1 to 56\]) * Post-treatment Period (Visits 60 to 64 \[Days 57 to 84\]) Enrolled participants (those accepted into the screening period of the trial who signed an informed consent form) will be stratified at randomization by extent of pulmonary TB; an equal number of participants with and without cavities visible in the lung fields on baseline chest radiograph will be allocated to each treatment group. A total of approximately 430 male or female participants aged 18 to 64 years, inclusive, with pulmonary, sputum culture-positive MDR TB (TB caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin) or with sputum smears positive for acid fast bacilli (AFB) and a positive rapid test for rifampicin resistance on direct sputum within 60 days prior to the expected date of enrollment. Participants with positive AFB smears and a positive rapid rifampicin resistance test will be enrolled as presumptively culture positive and withdrawn as ineligible if they are confirmed to not have sputum culture positive MDR TB.

Interventions

DRUGDelamanid

Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening.

DRUGOptimized Background Regimen (OBR)

Selection and administration of the treatment medications (i.e., OBRs) was based on World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country. Study Investigator could change OBR for a participant based on participant's tolerability and drug susceptibility testing (DST) results.

DRUGPlacebo

Placebo tablets matching 50-mg tablets of delamanid

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to 64 Years

Healthy volunteers

Inclusion criteria

* Provide written, informed consent prior to all trial-related procedures * Male and female participants aged between 18 and 64 years, inclusive. * Either mycobacterial culture of sputum positive for growth of Mycobacterium tuberculosis or sputum smear positive for acid fast bacilli within 60 days prior to the expected date of enrollment. * Participant with TB caused by isolates of Mycobacterium tuberculosis complex confirmed to be resistant to treatment with isoniazid and rifampicin, or with positive rapid test for rifampicin resistance on direct sputum positive for acid fast bacilli within 60 days prior to the expected date of enrollment. * Findings on chest radiograph consistent with TB. * Able to produce sputum for mycobacterial culture. * Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control (for example, two of the following precautions: tubal ligation, vaginal diaphragm, intrauterine device, oral contraceptives, contraceptive implant, combined hormonal patch, combined injectable contraceptive or depot-medroxyprogesterone acetate) throughout the participation in the trial and for 22 weeks after last dose (to cover duration of ovulation). * Male participants must agree to use an adequate method of contraception (double barrier) throughout the participation in the trial and for 30 weeks after last dose (to cover duration of spermatogenesis).

Exclusion criteria

* A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time. * Use of the medications including: use of amiodarone at any time during the previous 12 months, use of other anti-arrhythmics for the previous 30 days, and use of certain other medications, including certain anti-depressants, anti-histamines, and macrolides, for the previous 14 days. * Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels ≥265 micromol/L or hepatic impairment characterized by alanine transaminase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range. * Current clinically relevant changes in the electrocardiogram (ECG) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (in both male and female participants), or of either the QT interval corrected by Fridericia's formula (QTcF) or QT interval corrected by Bazett's formula (QTcB) interval over 430 milliseconds in male participants and 450 milliseconds in female participants. * Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction. * For participants with human immunodeficiency virus (HIV) infection, cluster of differentiation 4 helper/inducer T cell\[s\] (CD4) cell count \< 350/mm3 or on treatment with anti-retroviral medication for HIV infection. * Karnofsky score \< 60%. * Any diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated. * Evidence of clinically significant metabolic, gastrointestinal, neurological, psychiatric or endocrine diseases, malignancy, or other abnormalities (other than the indication being studied). * Known or suspected alcohol abuse, that is, abuse sufficient enough to compromise the safety or cooperation of the participant in the opinion of the investigator. * Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 (Screening \[Days -9 to -3\]). * Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form. * Recent use of methadone, benzodiazepines, cocaine, amphetamine/metamphetamine, tetrahydrocannabinol, barbiturates, tricyclic antidepressants, and opiates as determined by a urine drug screen unless evidence is provided that the positive drug screen is the result of authorized medications products prescribed by a physician for a non-abuse-related indication. * Any disorder that in the judgment of the investigator makes the participant not a good candidate for the trial or may prevent the participant from reliably participating in the entire course of the trial.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System	From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)	Sputum culture conversion was defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of Mycobacterium tuberculosis (MTB) followed by at least one additional sputum specimen with mycobacterial culture negative for growth at least 27 days after the first negative specimen and not followed by any sputum specimens positive for growth in the MGIT system at any point during the remainder of the 84-day trial after the first negative culture.
Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Time to maximum (peak) plasma concentration following the first daily dose (Cmax1) was reported as tmax1 and time to maximum (peak) plasma concentration following the second daily dose (Cmax2) was reported as tmax2. Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Maximum (peak) plasma concentration following the first daily dose was reported as Cmax1 and maximum (peak) plasma concentration following the second daily dose was reported as Cmax2. Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.
Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Rac (Cmax) up to Day 56 was collected on Days 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was computed.
Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Rac (AUC) up to Day 56 was collected on Days 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was computed.
Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.
Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.
Accumulation Ratio for Cmax (Rac[Cmax]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Rac (Cmax) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, pharmacokinetic (PK) analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (Cmax) was not available.
Accumulation Ratio for AUC (Rac[AUC]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56	Data for Rac (AUC) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (AUC) was not available.
Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose on Day 56	—

Secondary

Measure	Time frame	Description
Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments	From first dose of study drug up to post treatment period (Day 84)	—
Percentage of Participants With Clinically Significant Vital Sign Abnormalities	From first dose of study drug up to post treatment period (Day 84)	Criteria for potentially clinically significant vital sign abnormalities: Heart rate \[beats per minute (BPM)\]: \>=120, increase \>=15, \<=60, decrease \>=15; systolic blood pressure \[millimeter of mercury (mmHg)\]: \>=160, increase \>=20, \<=90, decrease \>=20; diastolic blood pressure (mmHg): \>=105, increase \>=15, \<=50, decrease \>=15; weight (kg) gain: increase \>=5%; or weight loss: decrease \>=5%; temperature \[degrees Celsius (C)\]: \>=38.5, increase of \>=1.1. Only categories with at least 1 participant with event are reported.
Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Baseline up to Day 56	Criteria for categorical changes in 6 12-lead Electrocardiogram results: Vent Rate Outliers Notable Decreases- \>= 25% decrease from Baseline and ventricular rate \< 50 beats per minute (beats/min), notable increases- \>= 25% decrease from Baseline and ventricular rate \> 100 beats/min; PR outliers notable changes- \>= 25% change from Baseline when PR \> 200 milliseconds (msec); QRS outliers notable changes- \>= 25% change from Baseline when QRS \> 100 msec; QT new onset (\> 500 msec); QT correction with Bazett formula (QTcB) and QT interval with Fridericia's correction (QTcF) new onset \> 500 msec, \> 480 msec, \> 450 msec, where new onset (\> 450, 480, 500 msec) means a participant who attains a value \> 450, 480, 500 msec during Treatment Period but not at each Baseline Visit; change \>= 30, \<= 60 msec; change \> 60 msec; and new abnormal U waves, ST segment changes, T wave changes, abnormal rhythm, RBBB, LBBB, myocardial infarction(MI). Only categories with at least 1 participant with event are r
Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	From first dose of study drug up to post treatment period (Day 84)	The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant laboratory values in clinical chemistry, hematology, coagulation, adrenal function tests, urinalysis and thyroid function tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. The categories with at least one participant with abnormal lab value as assessed by the investigator are reported.
Percentage of Participants With Clinically Significant Audiometry Findings	From first dose of study drug up to post treatment period (Day 84)	—
Percentage of Participants Using Concomitant Medications	From first dose of study drug up to post treatment period (Day 84)	The concomitant anti-TB medication were classified as per WHO 2008 guidelines and included: Category 1- first-line oral anti-tuberculosis drugs; Category 2- injectable anti-tuberculosis drugs; Category 3- fluoroquinolones; Category 4- oral bacteriostatic second-line anti-tuberculosis drugs; Category 5- anti-tuberculosis drugs with unclear efficacy or unclear role in MDR-TB treatment (not recommended by WHO for routine use in MDR-TB participants).
Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)	From first dose of study drug up to post treatment period (Day 84)	An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including e.g., an abnormal laboratory assessment result), symptom or disease temporally associated with participation in the clinical trial, whether or not it is considered causally related to the medicinal product or procedures of the clinical trial. A clinically significant worsening in the health of the participant compared with the participant's health status documented at baseline constituted a TEAE.
Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media	From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)	A participant achieving SCC using solid culture media was defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84.
Mean Change From Baseline in QTcF	Baseline, Days 1, 14, 28 and 56	—
Mean Change From Baseline in QTcB	Baseline, Days 1, 14, 28 and 56	—
Mean Change From Baseline in Ventricular Rate	Baseline, Days 1, 14, 28 and 56	—
Mean Change From Baseline in PR Interval	Baseline, Days 1, 14, 28 and 56	—
Mean Change From Baseline in QRS Interval	Baseline, Days 1, 14, 28 and 56	—
Mean Change From Baseline in QT Interval	Baseline, Days 1, 14, 28 and 56	—
Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Baseline, Days 1, 14, 28 and 56	Any changes in the ECG waves or segments as assessed by the investigator were reported.
Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Baseline, and 2, 3, 4, 10, 12, and 24 hours post dose on Day 56	—
Change From Baseline in Time to Culture Positivity Using the MGIT System	Baseline, Day 84	Mean change from baseline in time to culture positivity using the MGIT system was the value for time to results when a sputum culture result was positive (in days) using the MGIT system during the routine 42-day incubation period. A longer time to culture positivity represented a lower burden of MTB organisms present in the sputum. Baseline was defined as the average of Day -1 and Day 1 values, if the cultures on both days were positive; if only one culture was positive, the value for the positive culture was used as baseline.
Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System	Baseline to Day 57	AUC of change from baseline for time to culture positivity (i.e., TTD) (Days 0 to 57), summarizes overall participant response for treatment period. Larger AUC of change from baseline for time to culture positivity would strongly suggest a clinical response with reduction of burden of MTB organisms in sputum. For this analysis, ti=visit day of each visit; t0=Day 0, t1=Day 8, t2=Day 15, etc. and xi=change from baseline in time to culture positivity at each visit; AUC at each visit was determined as AUCi=(ti - ti-1)(xi+ xi-1)/2. Average AUC of change from baseline was the sum of all AUCi divided by a given participant's duration in the trial up to 57 days. Baseline (Day 0)=the average of Day -1 and Day 1 values, if cultures on both days were positive; if only one culture was positive, value for time to culture positivity for positive culture was used as baseline.
Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results	Day 57	—
Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results	Day 57 and Day 84	—
Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results	Day 57	—
Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results	Day 57 and Day 84	—
Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship	From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)	A participant achieving SCC using solid media is defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84. A dose response in the percentage of participants achieving SCC using the MGIT system was tested by the Cochran-Armitage linear trend test with equally spaced dose scores (0, 1, and 2 for placebo, 100 mg BID, and 200 mg BID, respectively).
Percentage of Participants Who Achieved Initial SCC Using the MGIT System	Day 57	Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using the MGIT system followed by at least one additional MGIT negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens MGIT positive for growth at any point between the negative MGIT sputum specimens. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media	Day 57	Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using solid culture media that was followed by at least one additional negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens positive for growth on solid culture media at any point between the negative sputum specimens using solid culture media. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Percentage of Participants Who Achieved Final SCC Using MGIT	Day 57	Final SCC was defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.
Percentage of Participants Who Achieved Final SCC Using Solid Culture Media	Day 57	Final SCC is defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.

Countries

China, Egypt, Estonia, Japan, Latvia, Peru, Philippines, South Korea, United States

Participant flow

Recruitment details

Participants took part in the study at 17 investigative sites in the Philippines, Latvia, Estonia, South Korea, Peru, China, Japan, Egypt, and the United States from 08 May 2008 to 11 June 2010.

Pre-assignment details

Participants with pulmonary sputum culture-positive, multidrug-resistant tuberculosis were randomized in 1:1:1 ratio to 1 of the 3 groups to receive either optimized background regimen (OBR) + 100 milligrams (mg) BID delamanid or OBR + 200 mg BID delamanid or OBR + placebo.

Participants by arm

Arm	Count
Delamanid 100 mg BID + OBR Participants received delamanid 100 mg (two 50 mg tablets), orally, BID with two matching placebo tablets plus OBR for 56 consecutive days (from Day 1 to Day 56). Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.	161
Delamanid 200 mg BID + OBR Participants received delamanid 200 mg (four 50 mg tablets), orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56). Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.	160
Placebo + OBR Participants received four placebo tablets matching 50-mg tablets of delamanid, orally, BID plus OBR for 56 consecutive days (from Day 1 to Day 56). Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment, in conjunction with national TB program guidelines in each country.	160
Total	481

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	4	6	4
Overall Study	Lost to Follow-up	0	1	2
Overall Study	Protocol Deviation	0	1	1
Overall Study	Subject Met (Protocol Specified) Withdrawal Criteria	1	0	2
Overall Study	Subject was Withdrawn From Participation by the Investigator	0	4	1
Overall Study	Subject Withdrew Consent to Participate	13	2	5

Baseline characteristics

Characteristic	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR	Placebo + OBR	Total
Age, Continuous	37.4 years STANDARD_DEVIATION 12.1	35.4 years STANDARD_DEVIATION 12	36.1 years STANDARD_DEVIATION 11.4	36.3 years STANDARD_DEVIATION 11.8
Ethnicity (NIH/OMB) Hispanic or Latino	42 Participants	44 Participants	47 Participants	133 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	118 Participants	116 Participants	113 Participants	347 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants	0 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Race Asian	82 Participants	87 Participants	88 Participants	257 Participants
Race/Ethnicity, Customized Race Black or African American	0 Participants	1 Participants	0 Participants	1 Participants
Race/Ethnicity, Customized Race Other	41 Participants	41 Participants	46 Participants	128 Participants
Race/Ethnicity, Customized Race White	38 Participants	31 Participants	26 Participants	95 Participants
Sex: Female, Male Female	56 Participants	52 Participants	49 Participants	157 Participants
Sex: Female, Male Male	105 Participants	108 Participants	111 Participants	324 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 161	1 / 160	0 / 160
other Total, other adverse events	145 / 161	148 / 160	147 / 160
serious Total, serious adverse events	16 / 161	20 / 160	14 / 160

Outcome results

Primary

Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid

Data for Rac (AUC) up to Day 56 was collected on Days 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was computed.

Time frame: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 14: Rac AUC0-24h	3.14 ratio	Standard Deviation 0.965
Delamanid 100 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 28: Rac AUC0-24h	3.35 ratio	Standard Deviation 1.24
Delamanid 100 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 56: Rac AUC0-24h	3.41 ratio	Standard Deviation 1.19
Delamanid 200 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 14: Rac AUC0-24h	3.13 ratio	Standard Deviation 1.06
Delamanid 200 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 28: Rac AUC0-24h	3.33 ratio	Standard Deviation 1.12
Delamanid 200 mg BID + OBR	Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid	Day 56: Rac AUC0-24h	3.52 ratio	Standard Deviation 1.38

Primary

Accumulation Ratio for AUC (Rac[AUC]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Data for Rac (AUC) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (AUC) on Days 14, 28 or 56 compared to AUC0-24h on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (AUC) was not available.

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: Due to limited measurable data as the metabolite concentration was below the level of detection on Day 1 for delamanid metabolites, PK analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (AUC) was not available.

Primary

Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid

Data for Rac (Cmax) up to Day 56 was collected on Days 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was computed.

Time frame: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 14: Rac Cmax1	3.05 ratio	Standard Deviation 1.28
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 14: Rac Cmax2	2.65 ratio	Standard Deviation 1.11
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 28: Rac Cmax1	3.35 ratio	Standard Deviation 1.63
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 28: Rac Cmax2	2.85 ratio	Standard Deviation 1.65
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 56: Rac Cmax1	3.37 ratio	Standard Deviation 1.46
Delamanid 100 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 56: Rac Cmax2	2.92 ratio	Standard Deviation 1.43
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 56: Rac Cmax1	5.09 ratio	Standard Deviation 18
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 14: Rac Cmax1	4.74 ratio	Standard Deviation 19.5
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 28: Rac Cmax2	2.65 ratio	Standard Deviation 1.01
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 14: Rac Cmax2	2.43 ratio	Standard Deviation 0.87
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 56: Rac Cmax2	2.81 ratio	Standard Deviation 1.19
Delamanid 200 mg BID + OBR	Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid	Day 28: Rac Cmax1	4.94 ratio	Standard Deviation 18

Primary

Accumulation Ratio for Cmax (Rac[Cmax]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Data for Rac (Cmax) up to Day 56 was to be collected on Days 1, 14, 28 and 56. Rac (Cmax) on Days 14, 28 or 56 compared to Cmax on Day 1 was to be computed. Due to limited measurable data on Day 1 for delamanid metabolites, pharmacokinetic (PK) analysis was not conducted on Day 1 data for delamanid metabolites, and data for Rac (Cmax) was not available.

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Primary

Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid

Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 1: AUC0-24h	2441 hoursnanograms (hng)/mL	Standard Deviation 880
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 14: AUC0-24h	7234 hoursnanograms (hng)/mL	Standard Deviation 2346
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 28: AUC0-24h	7700 hoursnanograms (hng)/mL	Standard Deviation 2322
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 56: AUC0-24h	7925 hoursnanograms (hng)/mL	Standard Deviation 2973
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 56: AUC0-24h	11837 hoursnanograms (hng)/mL	Standard Deviation 3975
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 1: AUC0-24h	3598 hoursnanograms (hng)/mL	Standard Deviation 1312
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 28: AUC0-24h	11251 hoursnanograms (hng)/mL	Standard Deviation 3626
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid	Day 14: AUC0-24h	10490 hoursnanograms (hng)/mL	Standard Deviation 3377

Primary

Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Data for AUC0-24h up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point for the specified category.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 28	1022 h*ng/mL	Standard Deviation 679
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 14	528 h*ng/mL	Standard Deviation 360
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 14	685 h*ng/mL	Standard Deviation 339
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 28	1424 h*ng/mL	Standard Deviation 757
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 14	1597 h*ng/mL	Standard Deviation 632
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 56	2285 h*ng/mL	Standard Deviation 992
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 28	1004 h*ng/mL	Standard Deviation 474
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 14	396 h*ng/mL	Standard Deviation 193
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 14	848 h*ng/mL	Standard Deviation 647
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 28	822 h*ng/mL	Standard Deviation 353
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 56	1256 h*ng/mL	Standard Deviation 643
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 56	1206 h*ng/mL	Standard Deviation 474
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 28	2480 h*ng/mL	Standard Deviation 1051
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 14	65.4 h*ng/mL	Standard Deviation 49.7
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 14	108 h*ng/mL	Standard Deviation 81.9
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 28	103 h*ng/mL	Standard Deviation 92.9
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 56	1251 h*ng/mL	Standard Deviation 766
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 56	132 h*ng/mL	Standard Deviation 118
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 28	349 h*ng/mL	Standard Deviation 240
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 14	482 h*ng/mL	Standard Deviation 475
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 56	3125 h*ng/mL	Standard Deviation 1397
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 28	655 h*ng/mL	Standard Deviation 695
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 56	720 h*ng/mL	Standard Deviation 436
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 56	699 h*ng/mL	Standard Deviation 489
Delamanid 100 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: AUC0-24h at Day 1	NA h*ng/mL	—
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 56	1191 h*ng/mL	Standard Deviation 862
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: AUC0-24h at Day 1	NA h*ng/mL	—
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 14	1192 h*ng/mL	Standard Deviation 859
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 28	1610 h*ng/mL	Standard Deviation 1097
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: AUC0-24h at Day 56	1902 h*ng/mL	Standard Deviation 1252
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 14	2485 h*ng/mL	Standard Deviation 920
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 28	3857 h*ng/mL	Standard Deviation 1486
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: AUC0-24h at Day 56	4907 h*ng/mL	Standard Deviation 1987
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 14	992 h*ng/mL	Standard Deviation 525
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 28	1475 h*ng/mL	Standard Deviation 676
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: AUC0-24h at Day 56	1796 h*ng/mL	Standard Deviation 870
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 14	153 h*ng/mL	Standard Deviation 93.2
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 28	524 h*ng/mL	Standard Deviation 342
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: AUC0-24h at Day 56	1112 h*ng/mL	Standard Deviation 623
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 14	687 h*ng/mL	Standard Deviation 363
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 28	1800 h*ng/mL	Standard Deviation 726
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: AUC0-24h at Day 56	2954 h*ng/mL	Standard Deviation 994
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 14	551 h*ng/mL	Standard Deviation 222
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 28	1120 h*ng/mL	Standard Deviation 368
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: AUC0-24h at Day 56	1668 h*ng/mL	Standard Deviation 549
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 14	90.5 h*ng/mL	Standard Deviation 68.7
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 28	161 h*ng/mL	Standard Deviation 134
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: AUC0-24h at Day 56	210 h*ng/mL	Standard Deviation 154
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 14	707 h*ng/mL	Standard Deviation 589
Delamanid 200 mg BID + OBR	Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: AUC0-24h at Day 28	1013 h*ng/mL	Standard Deviation 883

Primary

Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose

Maximum (peak) plasma concentration following the first daily dose was reported as Cmax1 and maximum (peak) plasma concentration following the second daily dose was reported as Cmax2. Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 1: Cmax1	135 nanograms (ng)/mL	Standard Deviation 54.9
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 1: Cmax2	151 nanograms (ng)/mL	Standard Deviation 60.4
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 14: Cmax1	369 nanograms (ng)/mL	Standard Deviation 137
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 14: Cmax2	361 nanograms (ng)/mL	Standard Deviation 127
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 28: Cmax1	404 nanograms (ng)/mL	Standard Deviation 144
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 28: Cmax2	381 nanograms (ng)/mL	Standard Deviation 128
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 56: Cmax1	414 nanograms (ng)/mL	Standard Deviation 165
Delamanid 100 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 56: Cmax2	400 nanograms (ng)/mL	Standard Deviation 162
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 56: Cmax2	588 nanograms (ng)/mL	Standard Deviation 213
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 1: Cmax1	187 nanograms (ng)/mL	Standard Deviation 74.3
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 28: Cmax1	599 nanograms (ng)/mL	Standard Deviation 222
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 1: Cmax2	228 nanograms (ng)/mL	Standard Deviation 91.5
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 56: Cmax1	611 nanograms (ng)/mL	Standard Deviation 217
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 14: Cmax1	547 nanograms (ng)/mL	Standard Deviation 200
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 28: Cmax2	560 nanograms (ng)/mL	Standard Deviation 196
Delamanid 200 mg BID + OBR	Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose	Day 14: Cmax2	513 nanograms (ng)/mL	Standard Deviation 178

Primary

Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose on Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis for the specified category.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6717	265 hours	Standard Deviation 98.2
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6704	195 hours	Standard Deviation 115
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6705	231 hours	Standard Deviation 84.7
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6706	180 hours	Standard Deviation 43.1
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6718	302 hours	Standard Deviation 132
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6720	394 hours	Standard Deviation 158
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6721	168 hours	Standard Deviation 49.7
Delamanid 100 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6722	134 hours	Standard Deviation 85.1
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6722	148 hours	Standard Deviation 60.3
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6718	305 hours	Standard Deviation 131
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6704	191 hours	Standard Deviation 67.2
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6721	153 hours	Standard Deviation 53.1
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6705	233 hours	Standard Deviation 87.9
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6720	424 hours	Standard Deviation 192
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6706	184 hours	Standard Deviation 40.3
Delamanid 200 mg BID + OBR	Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	t1/2 for DM-6717	265 hours	Standard Deviation 115

Primary

Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Data for Cmax up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 28	48.9 ng/mL	Standard Deviation 31.4
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 14	26.6 ng/mL	Standard Deviation 20.2
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 14	32.5 ng/mL	Standard Deviation 15.9
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 28	66.5 ng/mL	Standard Deviation 34.9
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 14	78.3 ng/mL	Standard Deviation 35.1
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 56	107 ng/mL	Standard Deviation 46.6
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 28	47.1 ng/mL	Standard Deviation 22.1
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 14	19.5 ng/mL	Standard Deviation 11.7
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 14	40.9 ng/mL	Standard Deviation 29.9
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 28	39.4 ng/mL	Standard Deviation 17.1
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 56	59.2 ng/mL	Standard Deviation 30.5
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 56	57.4 ng/mL	Standard Deviation 22.6
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 28	121 ng/mL	Standard Deviation 57.4
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 14	3.19 ng/mL	Standard Deviation 2.26
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 14	5.44 ng/mL	Standard Deviation 4.04
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 28	4.95 ng/mL	Standard Deviation 4.37
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 56	60.6 ng/mL	Standard Deviation 37.7
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 56	6.38 ng/mL	Standard Deviation 5.65
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 28	16.9 ng/mL	Standard Deviation 11.7
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 14	23.1 ng/mL	Standard Deviation 22.1
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 56	151 ng/mL	Standard Deviation 67.3
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 28	31.2 ng/mL	Standard Deviation 31.8
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 56	34.7 ng/mL	Standard Deviation 20.5
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 56	33.3 ng/mL	Standard Deviation 23
Delamanid 100 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: Cmax at Day 1	NA ng/mL	—
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 56	56.1 ng/mL	Standard Deviation 39.7
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: Cmax at Day 1	NA ng/mL	—
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 14	57.1 ng/mL	Standard Deviation 40.7
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 28	78.3 ng/mL	Standard Deviation 53
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Cmax at Day 56	90.3 ng/mL	Standard Deviation 58.5
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 14	124 ng/mL	Standard Deviation 57.8
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 28	187 ng/mL	Standard Deviation 78.5
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Cmax at Day 56	233 ng/mL	Standard Deviation 94.5
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 14	46.5 ng/mL	Standard Deviation 24.2
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 28	69.9 ng/mL	Standard Deviation 32
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Cmax at Day 56	84.3 ng/mL	Standard Deviation 41.5
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 14	7.61 ng/mL	Standard Deviation 4.51
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 28	25.5 ng/mL	Standard Deviation 17
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Cmax at Day 56	53.4 ng/mL	Standard Deviation 30.3
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 14	32.6 ng/mL	Standard Deviation 17.1
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 28	84.9 ng/mL	Standard Deviation 34.5
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Cmax at Day 56	138 ng/mL	Standard Deviation 47.9
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 14	26.5 ng/mL	Standard Deviation 11.6
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 28	53.6 ng/mL	Standard Deviation 18.7
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Cmax at Day 56	79.3 ng/mL	Standard Deviation 26.3
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 14	4.38 ng/mL	Standard Deviation 3.35
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 28	7.74 ng/mL	Standard Deviation 6.37
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Cmax at Day 56	9.92 ng/mL	Standard Deviation 7.04
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 14	33.4 ng/mL	Standard Deviation 27.3
Delamanid 200 mg BID + OBR	Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Cmax at Day 28	48.5 ng/mL	Standard Deviation 41.3

Primary

Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System

Sputum culture conversion was defined to occur at the time of the collection of a sputum specimen with mycobacterial culture negative for growth of Mycobacterium tuberculosis (MTB) followed by at least one additional sputum specimen with mycobacterial culture negative for growth at least 27 days after the first negative specimen and not followed by any sputum specimens positive for growth in the MGIT system at any point during the remainder of the 84-day trial after the first negative culture.

Time frame: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)

Population: Modified Intent-to-Treat (MITT) Population included all participants who had sputum cultures positive for multidrug resistant tuberculosis (MDR TB) at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System	45.4 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System	41.9 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System	29.6 percentage of participants

p-value: =0.008395% CI: [1.107, 2.124]Cochran-Mantel-Haenszel

p-value: =0.039395% CI: [1.012, 1.98]Cochran-Mantel-Haenszel

Primary

Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: 0 hours (morning pre-dose), 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Arm	Measure	Group	Value (MEDIAN)
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 28	3.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 14	24.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 14	14.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 28	10.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 14	12.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 56	9.96 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 28	3.01 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 14	11.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 14	13.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 28	9.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 56	3.03 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 56	9.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 28	9.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 14	13.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 14	24.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 28	4.02 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 56	3.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 56	4.02 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 28	9.99 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 14	13.0 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 56	9.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 28	3.00 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 56	9.97 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 56	4.00 hours
Delamanid 100 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: Tmax at Day 1	NA hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 56	4.00 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	All Metabolites: Tmax at Day 1	NA hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 14	13.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 28	3.99 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6704: Tmax at Day 56	4.00 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 14	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 28	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6705: Tmax at Day 56	12.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 14	12.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 28	4.00 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6706: Tmax at Day 56	4.00 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 14	24.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 28	13.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6717: Tmax at Day 56	9.99 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 14	24.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 28	12.9 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6718: Tmax at Day 56	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 14	10.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 28	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6720: Tmax at Day 56	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 14	10.0 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 28	4.00 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6721: Tmax at Day 56	9.97 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 14	9.98 hours
Delamanid 200 mg BID + OBR	Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722	DM-6722: Tmax at Day 28	4.00 hours

Primary

Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose

Time to maximum (peak) plasma concentration following the first daily dose (Cmax1) was reported as tmax1 and time to maximum (peak) plasma concentration following the second daily dose (Cmax2) was reported as tmax2. Data for Tmax up to Day 56 was collected on Days 1, 14, 28 and 56.

Time frame: Pre-dose, 2, 3, 4, 10 (pre-evening dose), 12, 13, 14 and 24 hours post-dose up to Day 56

Population: All randomized participants who received at least one dose of study medication. Number analyzed is the number of participants with data available for analysis at the given time point.

Arm	Measure	Group	Value (MEDIAN)
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 1: tmax1	4.00 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 1: tmax2	14.0 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 14: tmax1	3.02 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 14: tmax2	14.0 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 28: tmax1	3.02 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 28: tmax2	14.0 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 56: tmax1	3.02 hours
Delamanid 100 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 56: tmax2	14.0 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 56: tmax2	14.0 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 1: tmax1	4.00 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 28: tmax1	3.00 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 1: tmax2	14.0 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 56: tmax1	3.02 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 14: tmax1	3.00 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 28: tmax2	14.0 hours
Delamanid 200 mg BID + OBR	Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose	Day 14: tmax2	14.0 hours

Secondary

Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System

AUC of change from baseline for time to culture positivity (i.e., TTD) (Days 0 to 57), summarizes overall participant response for treatment period. Larger AUC of change from baseline for time to culture positivity would strongly suggest a clinical response with reduction of burden of MTB organisms in sputum. For this analysis, ti=visit day of each visit; t0=Day 0, t1=Day 8, t2=Day 15, etc. and xi=change from baseline in time to culture positivity at each visit; AUC at each visit was determined as AUCi=(ti - ti-1)(xi+ xi-1)/2. Average AUC of change from baseline was the sum of all AUCi divided by a given participant's duration in the trial up to 57 days. Baseline (Day 0)=the average of Day -1 and Day 1 values, if cultures on both days were positive; if only one culture was positive, value for time to culture positivity for positive culture was used as baseline.

Time frame: Baseline to Day 57

Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system. Overall number analyzed are the participants with data available for analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System	13.4 days	Standard Error 0.7
Delamanid 200 mg BID + OBR	Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System	13.1 days	Standard Error 0.7
Placebo + OBR	Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System	11.1 days	Standard Error 0.7

p-value: =0.0246ANCOVA

p-value: =0.0529ANCOVA

p-value: =0.7508ANCOVA

Secondary

Change From Baseline in Time to Culture Positivity Using the MGIT System

Mean change from baseline in time to culture positivity using the MGIT system was the value for time to results when a sputum culture result was positive (in days) using the MGIT system during the routine 42-day incubation period. A longer time to culture positivity represented a lower burden of MTB organisms present in the sputum. Baseline was defined as the average of Day -1 and Day 1 values, if the cultures on both days were positive; if only one culture was positive, the value for the positive culture was used as baseline.

Time frame: Baseline, Day 84

Population: Last Observation Carried Forward(LOCF)Population:all randomized participants with positive sputum culture for MDR TB at baseline(pre-dose)by MGIT system and when sputum collection was not possible,a specimen was contaminated with other bacteria,or a result was missing due to a participant withdrawing from trial, the preceding non-missing result for that variable at a postbaseline visit was carried forward. Overall number analyzed=participants with data available for analysis.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Change From Baseline in Time to Culture Positivity Using the MGIT System	25.9 days	Standard Error 1
Delamanid 200 mg BID + OBR	Change From Baseline in Time to Culture Positivity Using the MGIT System	26.0 days	Standard Error 1
Placebo + OBR	Change From Baseline in Time to Culture Positivity Using the MGIT System	24.2 days	Standard Error 1.1

p-value: =0.2419ANCOVA

p-value: =0.2239ANCOVA

p-value: =0.9544ANCOVA

Secondary

Mean Change From Baseline in PR Interval

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 1	-1.3 msec	Standard Deviation 5.6
Delamanid 100 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 14	-0.7 msec	Standard Deviation 7.7
Delamanid 100 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 28	-1.4 msec	Standard Deviation 8.1
Delamanid 100 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 56	-1.6 msec	Standard Deviation 8.3
Delamanid 200 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 56	0.3 msec	Standard Deviation 8.1
Delamanid 200 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 1	-1.0 msec	Standard Deviation 4.8
Delamanid 200 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 28	-0.8 msec	Standard Deviation 8.4
Delamanid 200 mg BID + OBR	Mean Change From Baseline in PR Interval	Day 14	-0.8 msec	Standard Deviation 7.2
Placebo + OBR	Mean Change From Baseline in PR Interval	Day 56	-0.5 msec	Standard Deviation 7.2
Placebo + OBR	Mean Change From Baseline in PR Interval	Day 14	-1.4 msec	Standard Deviation 8.1
Placebo + OBR	Mean Change From Baseline in PR Interval	Day 28	-0.6 msec	Standard Deviation 7.4
Placebo + OBR	Mean Change From Baseline in PR Interval	Day 1	-1.6 msec	Standard Deviation 5.4

Secondary

Mean Change From Baseline in QRS Interval

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 1	-0.3 msec	Standard Deviation 2.8
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 14	0.1 msec	Standard Deviation 3.3
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 28	0.4 msec	Standard Deviation 3.6
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 56	0.7 msec	Standard Deviation 4.1
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 56	-0.2 msec	Standard Deviation 4
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 1	-0.5 msec	Standard Deviation 2.8
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 28	-0.1 msec	Standard Deviation 4.2
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QRS Interval	Day 14	0.1 msec	Standard Deviation 3.5
Placebo + OBR	Mean Change From Baseline in QRS Interval	Day 56	0.2 msec	Standard Deviation 3.8
Placebo + OBR	Mean Change From Baseline in QRS Interval	Day 14	-0.1 msec	Standard Deviation 3.9
Placebo + OBR	Mean Change From Baseline in QRS Interval	Day 28	-0.3 msec	Standard Deviation 3.8
Placebo + OBR	Mean Change From Baseline in QRS Interval	Day 1	-0.2 msec	Standard Deviation 3.3

Secondary

Mean Change From Baseline in QTcB

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcB	Day 14	6.5 msec	Standard Deviation 11.5
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcB	Day 56	11.7 msec	Standard Deviation 14.5
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcB	Day 28	7.9 msec	Standard Deviation 12.1
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcB	Day 1	0.8 msec	Standard Deviation 7.4
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcB	Day 28	12.5 msec	Standard Deviation 14
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcB	Day 56	14.6 msec	Standard Deviation 12.6
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcB	Day 14	8.1 msec	Standard Deviation 10.7
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcB	Day 1	1.5 msec	Standard Deviation 7.2
Placebo + OBR	Mean Change From Baseline in QTcB	Day 56	2.3 msec	Standard Deviation 13.6
Placebo + OBR	Mean Change From Baseline in QTcB	Day 1	-0.4 msec	Standard Deviation 8.5
Placebo + OBR	Mean Change From Baseline in QTcB	Day 28	2.1 msec	Standard Deviation 13
Placebo + OBR	Mean Change From Baseline in QTcB	Day 14	0.5 msec	Standard Deviation 12

Secondary

Mean Change From Baseline in QTcF

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcF	Day 1	0.1 msec	Standard Deviation 7.1
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcF	Day 14	7.7 msec	Standard Deviation 11.1
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcF	Day 28	9.9 msec	Standard Deviation 12.3
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QTcF	Day 56	14.9 msec	Standard Deviation 14.3
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcF	Day 56	17.5 msec	Standard Deviation 13.9
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcF	Day 1	0.0 msec	Standard Deviation 7.1
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcF	Day 28	14.1 msec	Standard Deviation 13.2
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QTcF	Day 14	9.3 msec	Standard Deviation 11.2
Placebo + OBR	Mean Change From Baseline in QTcF	Day 56	2.7 msec	Standard Deviation 12.2
Placebo + OBR	Mean Change From Baseline in QTcF	Day 14	0.8 msec	Standard Deviation 11
Placebo + OBR	Mean Change From Baseline in QTcF	Day 28	2.4 msec	Standard Deviation 11.2
Placebo + OBR	Mean Change From Baseline in QTcF	Day 1	-1.8 msec	Standard Deviation 8.3

Secondary

Mean Change From Baseline in QT Interval

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 1	-1.0 msec	Standard Deviation 11.5
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 14	9.5 msec	Standard Deviation 18.2
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 28	13.4 msec	Standard Deviation 20.3
Delamanid 100 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 56	20.1 msec	Standard Deviation 23.5
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 56	22.0 msec	Standard Deviation 28.4
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 1	-2.7 msec	Standard Deviation 10.9
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 28	16.3 msec	Standard Deviation 21.1
Delamanid 200 mg BID + OBR	Mean Change From Baseline in QT Interval	Day 14	11.1 msec	Standard Deviation 20.1
Placebo + OBR	Mean Change From Baseline in QT Interval	Day 56	3.1 msec	Standard Deviation 21.7
Placebo + OBR	Mean Change From Baseline in QT Interval	Day 14	1.1 msec	Standard Deviation 18.5
Placebo + OBR	Mean Change From Baseline in QT Interval	Day 28	2.5 msec	Standard Deviation 20.2
Placebo + OBR	Mean Change From Baseline in QT Interval	Day 1	-4.3 msec	Standard Deviation 11.6

Secondary

Mean Change From Baseline in Ventricular Rate

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 1	0.9 beats/min	Standard Deviation 5.5
Delamanid 100 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 14	-1.9 beats/min	Standard Deviation 8.1
Delamanid 100 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 28	-3.2 beats/min	Standard Deviation 8.6
Delamanid 100 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 56	-4.8 beats/min	Standard Deviation 10.3
Delamanid 200 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 56	-4.7 beats/min	Standard Deviation 12.6
Delamanid 200 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 1	2.0 beats/min	Standard Deviation 4.9
Delamanid 200 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 28	-3.2 beats/min	Standard Deviation 9.3
Delamanid 200 mg BID + OBR	Mean Change From Baseline in Ventricular Rate	Day 14	-2.1 beats/min	Standard Deviation 9
Placebo + OBR	Mean Change From Baseline in Ventricular Rate	Day 56	-1.2 beats/min	Standard Deviation 10.6
Placebo + OBR	Mean Change From Baseline in Ventricular Rate	Day 14	-0.6 beats/min	Standard Deviation 8.6
Placebo + OBR	Mean Change From Baseline in Ventricular Rate	Day 28	-0.8 beats/min	Standard Deviation 10.2
Placebo + OBR	Mean Change From Baseline in Ventricular Rate	Day 1	1.9 beats/min	Standard Deviation 5.3

Secondary

Percentage of Participants Using Concomitant Medications

The concomitant anti-TB medication were classified as per WHO 2008 guidelines and included: Category 1- first-line oral anti-tuberculosis drugs; Category 2- injectable anti-tuberculosis drugs; Category 3- fluoroquinolones; Category 4- oral bacteriostatic second-line anti-tuberculosis drugs; Category 5- anti-tuberculosis drugs with unclear efficacy or unclear role in MDR-TB treatment (not recommended by WHO for routine use in MDR-TB participants).

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.

Arm	Measure	Group	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Medications (Excluding Anti-TB Medications)	98.8 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 1	90.7 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 2	88.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 3	97.5 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 4	99.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 5	26.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 5	27.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Medications (Excluding Anti-TB Medications)	98.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 3	98.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 4	98.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 1	90.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 2	80.0 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 1	88.8 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 2	88.8 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 5	27.5 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 3	98.1 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Medications (Excluding Anti-TB Medications)	98.8 percentage of participants
Placebo + OBR	Percentage of Participants Using Concomitant Medications	Concomitant Anti-TB Medications: Category 4	99.4 percentage of participants

Secondary

Percentage of Participants Who Achieved Final SCC Using MGIT

Final SCC was defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.

Time frame: Day 57

Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Final SCC Using MGIT	45.4 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Final SCC Using MGIT	41.9 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Final SCC Using MGIT	29.6 percentage of participants

p-value: =0.005695% CI: [1.152, 2.591]Stratified Log-Rank Test

p-value: =0.023295% CI: [1.048, 2.399]Stratified Log-Rank Test

Secondary

Percentage of Participants Who Achieved Final SCC Using Solid Culture Media

Final SCC is defined as SCC at Day 57 or the latest time point of the first negative sputum culture establishing SCC for a given participant after the last positive sputum culture observed during the 56-day treatment period, whichever comes first. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.

Time frame: Day 57

Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Final SCC Using Solid Culture Media	53.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Final SCC Using Solid Culture Media	65.2 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Final SCC Using Solid Culture Media	33.6 percentage of participants

p-value: =0.001695% CI: [1.235, 2.759]Stratified Log-Rank Test

p-value: <0.000195% CI: [1.555, 3.405]Stratified Log-Rank Test

Secondary

Percentage of Participants Who Achieved Initial SCC Using the MGIT System

Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using the MGIT system followed by at least one additional MGIT negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens MGIT positive for growth at any point between the negative MGIT sputum specimens. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.

Time frame: Day 57

Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Initial SCC Using the MGIT System	50.4 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Initial SCC Using the MGIT System	50.0 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Initial SCC Using the MGIT System	31.2 percentage of participants

p-value: =0.001195% CI: [1.255, 2.745]Stratified Log-Rank Test

p-value: =0.001395% CI: [1.246, 2.743]Stratified Log-Rank Test

Secondary

Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media

Initial SCC occurred at the time of the collection of the first sputum specimen with mycobacterial culture negative for growth of MTB using solid culture media that was followed by at least one additional negative sputum specimen at least 27 days after the first negative specimen and no sputum specimens positive for growth on solid culture media at any point between the negative sputum specimens using solid culture media. Survival analysis methodology was performed to compare the Kaplan-Meier curves for time to SCC across 3 treatment groups. Comparisons between 100 mg BID and placebo and 200 mg BID and placebo were also performed with stratified log-rank tests. The benefit ratios (ratio of likelihoods that participants treated with delamanid BID + OBR would achieve SCC more rapidly than participants treated with placebo + OBR) for participants achieving SCC were computed.

Time frame: Day 57

Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media	60.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media	68.7 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media	37.2 percentage of participants

p-value: =0.000495% CI: [1.315, 2.82]Stratified Log-Rank Test

p-value: <0.000195% CI: [1.504, 3.189]Stratified Log-Rank Test

Secondary

Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship

A participant achieving SCC using solid media is defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84. A dose response in the percentage of participants achieving SCC using the MGIT system was tested by the Cochran-Armitage linear trend test with equally spaced dose scores (0, 1, and 2 for placebo, 100 mg BID, and 200 mg BID, respectively).

Time frame: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)

Population: MITT Population included all participants who had sputum cultures positive for multidrug resistant tuberculosis (MDR TB) at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship	45.4 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship	41.9 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship	29.6 percentage of participants

p-value: =0.0468Cochran-Armitage Linear Trend Test

Secondary

Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media

A participant achieving SCC using solid culture media was defined as one with sputum culture negative for growth of MTB on Day 57, and (a) not followed by a positive culture at any point thereafter, and (b) confirmed by at least one additional negative sputum culture at Day 84.

Time frame: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 84)

Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media	53.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media	65.2 percentage of participants
Placebo + OBR	Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media	33.6 percentage of participants

p-value: =0.002195% CI: [1.175, 2.177]Cochran-Mantel-Haenszel

p-value: <0.000195% CI: [1.449, 2.595]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)

An adverse event (AE) was defined as any untoward medical occurrence in a clinical trial participant and which does not necessarily have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including e.g., an abnormal laboratory assessment result), symptom or disease temporally associated with participation in the clinical trial, whether or not it is considered causally related to the medicinal product or procedures of the clinical trial. A clinically significant worsening in the health of the participant compared with the participant's health status documented at baseline constituted a TEAE.

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)	90.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)	93.1 percentage of participants
Placebo + OBR	Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)	93.1 percentage of participants

Secondary

Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56

Criteria for categorical changes in 6 12-lead Electrocardiogram results: Vent Rate Outliers Notable Decreases- \>= 25% decrease from Baseline and ventricular rate \< 50 beats per minute (beats/min), notable increases- \>= 25% decrease from Baseline and ventricular rate \> 100 beats/min; PR outliers notable changes- \>= 25% change from Baseline when PR \> 200 milliseconds (msec); QRS outliers notable changes- \>= 25% change from Baseline when QRS \> 100 msec; QT new onset (\> 500 msec); QT correction with Bazett formula (QTcB) and QT interval with Fridericia's correction (QTcF) new onset \> 500 msec, \> 480 msec, \> 450 msec, where new onset (\> 450, 480, 500 msec) means a participant who attains a value \> 450, 480, 500 msec during Treatment Period but not at each Baseline Visit; change \>= 30, \<= 60 msec; change \> 60 msec; and new abnormal U waves, ST segment changes, T wave changes, abnormal rhythm, RBBB, LBBB, myocardial infarction(MI). Only categories with at least 1 participant with event are r

Time frame: Baseline up to Day 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change >= 30, <= 60 msec	36.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 450 msec)	39.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QT New Onset (> 500 msec)	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 450 msec)	15.5 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >= 30, <= 60 msec	36.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Increases	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 480 msec)	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >60 msec	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change > 60 msec	3.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 500 msec)	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)	2.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Decreases	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 480 msec)	7.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Abnormal Rhythm	9.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change >= 30, <= 60 msec	44.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Decreases	1.2 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Increases	2.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QT New Onset (> 500 msec)	1.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 500 msec)	1.2 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 480 msec)	8.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 450 msec)	37.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >= 30, <= 60 msec	44.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >60 msec	3.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 480 msec)	3.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 450 msec)	13.7 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change > 60 msec	3.7 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Abnormal Rhythm	10.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)	3.7 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Abnormal Rhythm	17.5 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 450 msec)	6.2 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 480 msec)	3.1 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 500 msec)	1.2 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change >= 30, <= 60 msec	15.6 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QT New Onset (> 500 msec)	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Decreases	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF Change > 60 msec	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	Vent Rate Outliers Notable Increases	3.7 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >60 msec	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB Change >= 30, <= 60 msec	17.5 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	New Right Bundle Branch Block (RBBB), Left Bundle Branch Block (LBBB), Myocardial Infarction (MI)	7.5 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcF New Onset (> 480 msec)	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56	QTcB New Onset (> 450 msec)	19.3 percentage of participants

Secondary

Percentage of Participants With Change in ECG Morphological Patterns From Baseline

Any changes in the ECG waves or segments as assessed by the investigator were reported.

Time frame: Baseline, Days 1, 14, 28 and 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New Abnormal U Waves	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New ST Segment Changes	1.8 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New T Wave Changes	9.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New Abnormal U Waves	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New ST Segment Changes	3.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New T Wave Changes	12.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New Abnormal U Waves	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New ST Segment Changes	1.8 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New T Wave Changes	11.8 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New Abnormal U Waves	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New ST Segment Changes	2.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New T Wave Changes	11.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New T Wave Changes	10.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New Abnormal U Waves	0.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New Abnormal U Waves	0.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New T Wave Changes	5.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New ST Segment Changes	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New T Wave Changes	5.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New ST Segment Changes	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New T Wave Changes	6.2 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New ST Segment Changes	0.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New ST Segment Changes	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New Abnormal U Waves	0.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New Abnormal U Waves	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New Abnormal U Waves	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New ST Segment Changes	1.2 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New Abnormal U Waves	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 14: New T Wave Changes	4.3 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New Abnormal U Waves	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New ST Segment Changes	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New ST Segment Changes	1.8 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New Abnormal U Waves	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New ST Segment Changes	1.2 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 28: New T Wave Changes	10.0 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 1: New T Wave Changes	6.2 percentage of participants
Placebo + OBR	Percentage of Participants With Change in ECG Morphological Patterns From Baseline	Day 56: New T Wave Changes	5.0 percentage of participants

Secondary

Percentage of Participants With Clinically Significant Audiometry Findings

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Audiometry Findings	0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Audiometry Findings	0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Audiometry Findings	0 percentage of participants

Secondary

Percentage of Participants With Clinically Significant Laboratory Test Abnormalities

The laboratory values were one of the parameters to measure the safety and tolerability of individual participants. Participants with potentially clinically significant laboratory values in clinical chemistry, hematology, coagulation, adrenal function tests, urinalysis and thyroid function tests that were identified based on pre-defined criteria were reported. Any value outside the normal range was flagged for the attention of the investigator who assessed whether or not a flagged value is of clinical significance. The categories with at least one participant with abnormal lab value as assessed by the investigator are reported.

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation. Number analyzed is the number of participants with at least one non-missing result for a given lab test.

Arm	Measure	Group	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Uric Acid (mg/dL) >12	24.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Gamma-glutamyl Transferase (U/L); Male >225.0, Female >175.0	3.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Platelet Count (thous/µL) <100, >600	16.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Creatinine (mg/dL) >2.0	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	White Blood Count Casts	100.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Mean Corpuscular Volume (femtoliter [fL]) <=78, >=105	30.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Cortisol, Serum (micrograms per deciliter [µg/dL]) >=26	36.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Urea Nitrogen (mg/dL) >34	1.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Cholesterol (mg/dL) >300.0	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Free Thyroxine (T4) [nanograms per deciliter (ng/dL)] <=.30, >=2.5	1.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Prothrombin Time (sec) >17.5	4.7 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Chloride (milliequivalents per liter [mEq/L]) <85	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Thyroid Stimulating Hormone (micro-international units per milliliter [µIU/mL]) <=.30 >=3	23.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hemoglobin (g/dL) <10, >16	28.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Calcium (mg/dL) <7, >11.5	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Albumin (grams per deciliter [g/dL]) <2.6	8.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Triglycerides (mg/dL) >300	4.3 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Aspartate aminotransferase (AST) (U/L) >150.0	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Alanine Transaminase (ALT) (units per liter [U/L]) >150.0	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Red Blood Cell (RBC) Count (million per microliter [mill/µL]) <4, >=6.5	31.7 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Eosinophils, Absolute (thousands per microliter [thous/µL]) >=0.8	14.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Sodium (mEq/L) <132, >148	17.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Reticulocyte Count (%) <=.1, >=3	21.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophil, Bands (%) >=8.0	2.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Protein, Total Serum (g/dL) >9.5	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	White Blood Count (thous/µL) <3, >=15	11.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Mean Corpuscular Hemoglobin (picograms [pg]) >40.0	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Lymphocytes, Absolute (thous/µL) >=5.0	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Blood (Urinalysis): Positive	55.8 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Activated Partial Thromboplastin Time (seconds [sec]) >45.0	14.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Potassium (mEq/L) <3, >5.5	16.1 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Epithelial Casts	100.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophils, Absolute (thous/µL) <=2.0	13.7 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Lactic Dehydrogenase (U/L) >400	1.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Granular Cast	100.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hematocrit (%); Male <32, >58, Female <27, >58	15.5 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Glucose (mg/dL) <50, >300	1.9 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hyaline Cast	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Potassium (mEq/L) <3, >5.5	18.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Mean Corpuscular Volume (femtoliter [fL]) <=78, >=105	26.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophil, Bands (%) >=8.0	2.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophils, Absolute (thous/µL) <=2.0	10.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Platelet Count (thous/µL) <100, >600	15.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Prothrombin Time (sec) >17.5	3.7 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Red Blood Cell (RBC) Count (million per microliter [mill/µL]) <4, >=6.5	23.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Reticulocyte Count (%) <=.1, >=3	21.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	White Blood Count (thous/µL) <3, >=15	12.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Blood (Urinalysis): Positive	58.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Epithelial Casts	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Granular Cast	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hyaline Cast	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	RBC Casts	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	White Blood Count Casts	100.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Cortisol, Serum (micrograms per deciliter [µg/dL]) >=26	48.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Free Thyroxine (T4) [nanograms per deciliter (ng/dL)] <=.30, >=2.5	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Thyroid Stimulating Hormone (micro-international units per milliliter [µIU/mL]) <=.30 >=3	20.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Albumin (grams per deciliter [g/dL]) <2.6	3.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Alanine Transaminase (ALT) (units per liter [U/L]) >150.0	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Aspartate aminotransferase (AST) (U/L) >150.0	1.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Bilirubin, Total (mg/dL) >2	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Calcium (mg/dL) <7, >11.5	1.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Chloride (milliequivalents per liter [mEq/L]) <85	2.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Cholesterol (mg/dL) >300.0	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Creatinine (mg/dL) >2.0	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Glucose (mg/dL) <50, >300	1.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Lactic Dehydrogenase (U/L) >400	3.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Sodium (mEq/L) <132, >148	16.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Triglycerides (mg/dL) >300	3.8 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Urea Nitrogen (mg/dL) >34	1.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Uric Acid (mg/dL) >12	27.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Activated Partial Thromboplastin Time (seconds [sec]) >45.0	12.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Eosinophils, Absolute (thousands per microliter [thous/µL]) >=0.8	18.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hematocrit (%); Male <32, >58, Female <27, >58	11.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hemoglobin (g/dL) <10, >16	23.1 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hyaline Cast	100.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Gamma-glutamyl Transferase (U/L); Male >225.0, Female >175.0	1.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Granular Cast	100.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Activated Partial Thromboplastin Time (seconds [sec]) >45.0	16.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Glucose (mg/dL) <50, >300	4.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Epithelial Casts	100.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Mean Corpuscular Volume (femtoliter [fL]) <=78, >=105	26.9 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Lactic Dehydrogenase (U/L) >400	1.9 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Blood (Urinalysis): Positive	55.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	White Blood Count (thous/µL) <3, >=15	13.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Potassium (mEq/L) <3, >5.5	18.1 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Reticulocyte Count (%) <=.1, >=3	23.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Red Blood Cell (RBC) Count (million per microliter [mill/µL]) <4, >=6.5	26.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Lymphocytes, Absolute (thous/µL) >=5.0	1.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Sodium (mEq/L) <132, >148	17.5 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Prothrombin Time (sec) >17.5	1.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Eosinophils, Absolute (thousands per microliter [thous/µL]) >=0.8	24.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Triglycerides (mg/dL) >300	4.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Platelet Count (thous/µL) <100, >600	13.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Mean Corpuscular Hemoglobin Concentrate (g/dL) >40.0	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Alanine Transaminase (ALT) (units per liter [U/L]) >150.0	1.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Albumin (grams per deciliter [g/dL]) <2.6	8.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Urea Nitrogen (mg/dL) >34	1.9 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Aspartate aminotransferase (AST) (U/L) >150.0	2.5 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophils, Absolute (thous/µL) <=2.0	13.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Thyroid Stimulating Hormone (micro-international units per milliliter [µIU/mL]) <=.30 >=3	26.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hemoglobin (g/dL) <10, >16	22.5 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Calcium (mg/dL) <7, >11.5	3.8 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Free Thyroxine (T4) [nanograms per deciliter (ng/dL)] <=.30, >=2.5	1.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Uric Acid (mg/dL) >12	22.9 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Chloride (milliequivalents per liter [mEq/L]) <85	0.6 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Cortisol, Serum (micrograms per deciliter [µg/dL]) >=26	29.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Neutrophil, Bands (%) >=8.0	1.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	RBC Casts	100.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Hematocrit (%); Male <32, >58, Female <27, >58	11.3 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Laboratory Test Abnormalities	Creatinine (mg/dL) >2.0	1.9 percentage of participants

Secondary

Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments	0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments	0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments	0 percentage of participants

Secondary

Percentage of Participants With Clinically Significant Vital Sign Abnormalities

Criteria for potentially clinically significant vital sign abnormalities: Heart rate \[beats per minute (BPM)\]: \>=120, increase \>=15, \<=60, decrease \>=15; systolic blood pressure \[millimeter of mercury (mmHg)\]: \>=160, increase \>=20, \<=90, decrease \>=20; diastolic blood pressure (mmHg): \>=105, increase \>=15, \<=50, decrease \>=15; weight (kg) gain: increase \>=5%; or weight loss: decrease \>=5%; temperature \[degrees Celsius (C)\]: \>=38.5, increase of \>=1.1. Only categories with at least 1 participant with event are reported.

Time frame: From first dose of study drug up to post treatment period (Day 84)

Population: ITT population included all randomized participants who received any amount of IMP, regardless of any protocol deviation or violation. Number analyzed is the number of participants who had at least one post-baseline numerical result for the given test.

Arm	Measure	Group	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Decrease of >=5% in Body Weight	16.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Increase of >=5% in Body Weight	35.2 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Temperature: >=38.5C + Increase of >=1.1C	0.0 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: <=60 BPM + Decrease of >=15	4.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: >=120 BPM + Increase of >=15	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: <=90 mmHg + Decrease of >=20 mmHg	4.4 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: >=160 mmHg + Increase of >=20 mmHg	0.6 percentage of participants
Delamanid 100 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Diastolic Blood Pressure <=50 mmHg + Decrease of >=15 mmHg	1.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Temperature: >=38.5C + Increase of >=1.1C	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: >=160 mmHg + Increase of >=20 mmHg	0.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: <=60 BPM + Decrease of >=15	5.1 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: >=120 BPM + Increase of >=15	0.6 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: <=90 mmHg + Decrease of >=20 mmHg	9.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Decrease of >=5% in Body Weight	13.9 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Increase of >=5% in Body Weight	32.3 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Diastolic Blood Pressure <=50 mmHg + Decrease of >=15 mmHg	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Temperature: >=38.5C + Increase of >=1.1C	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Increase of >=5% in Body Weight	44.6 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Weight: Decrease of >=5% in Body Weight	6.4 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: <=60 BPM + Decrease of >=15	2.5 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: >=160 mmHg + Increase of >=20 mmHg	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Systolic Blood Pressure: <=90 mmHg + Decrease of >=20 mmHg	8.9 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Heart Rate: >=120 BPM + Increase of >=15	0.0 percentage of participants
Placebo + OBR	Percentage of Participants With Clinically Significant Vital Sign Abnormalities	Diastolic Blood Pressure <=50 mmHg + Decrease of >=15 mmHg	0.6 percentage of participants

Secondary

Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results

Time frame: Day 57 and Day 84

Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results	60.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results	67.8 percentage of participants
Placebo + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results	45.1 percentage of participants

p-value: =0.019695% CI: [1.044, 1.722]Cochran-Mantel-Haenszel

p-value: =0.000695% CI: [1.183, 1.909]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results

Time frame: Day 57 and Day 84

Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results	50.4 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results	44.9 percentage of participants
Placebo + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results	40.8 percentage of participants

p-value: =0.120195% CI: [0.945, 1.612]Cochran-Mantel-Haenszel

p-value: =0.511295% CI: [0.829, 1.456]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results

Time frame: Day 57

Population: MITT (Solid Culture) Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using solid culture medium.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results	65.5 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results	71.3 percentage of participants
Placebo + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results	49.6 percentage of participants

p-value: =0.014195% CI: [1.053, 1.661]Cochran-Mantel-Haenszel

p-value: =0.000895% CI: [1.155, 1.791]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results

Time frame: Day 57

Population: MITT Population included all participants who had sputum cultures positive for MDR TB at baseline (Day -1 and/or Day 1) using the MGIT system.

Arm	Measure	Value (NUMBER)
Delamanid 100 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results	56.0 percentage of participants
Delamanid 200 mg BID + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results	52.9 percentage of participants
Placebo + OBR	Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results	44.0 percentage of participants

p-value: =0.051895% CI: [0.995, 1.627]Cochran-Mantel-Haenszel

p-value: =0.150695% CI: [0.934, 1.55]Cochran-Mantel-Haenszel

Secondary

Time-matched Change From Baseline (Day -1) in QTcF at Day 56

Time frame: Baseline, and 2, 3, 4, 10, 12, and 24 hours post dose on Day 56

Population: The ECG population included all participants who had at least one baseline and one on-treatment ECG (full data set).

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 2 Hours Post Dose	11.8 msec	Standard Deviation 16.3
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 3 Hours Post Dose	12.8 msec	Standard Deviation 16.6
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 4 Hours Post Dose	16.8 msec	Standard Deviation 16.3
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 10 Hours Post Dose	16.5 msec	Standard Deviation 17.4
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 12 Hours Post Dose	15.6 msec	Standard Deviation 17.4
Delamanid 100 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 24 Hours Post Dose	15.5 msec	Standard Deviation 18.9
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 24 Hours Post Dose	18.3 msec	Standard Deviation 18.5
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 2 Hours Post Dose	14.6 msec	Standard Deviation 18.8
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 10 Hours Post Dose	20.8 msec	Standard Deviation 17.3
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 12 Hours Post Dose	16.7 msec	Standard Deviation 17
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 3 Hours Post Dose	14.7 msec	Standard Deviation 16
Delamanid 200 mg BID + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 4 Hours Post Dose	19.4 msec	Standard Deviation 17.3
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 3 Hours Post Dose	-0.4 msec	Standard Deviation 14.5
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 4 Hours Post Dose	5.0 msec	Standard Deviation 15.8
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 24 Hours Post Dose	3.4 msec	Standard Deviation 15
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 10 Hours Post Dose	5.2 msec	Standard Deviation 15.5
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 2 Hours Post Dose	-0.5 msec	Standard Deviation 14.3
Placebo + OBR	Time-matched Change From Baseline (Day -1) in QTcF at Day 56	Day 56: 12 Hours Post Dose	2.6 msec	Standard Deviation 15.6

Source: ClinicalTrials.gov · Data processed: Mar 26, 2026

A Trial to Evaluate OPC 67683 in Participants With Pulmonary Sputum Culture-positive, Multidrug-resistant Tuberculosis (TB)

Conditions

Keywords

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Countries

Participant flow

Recruitment details

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Accumulation Ratio for AUC From Time 0 to 24 Hours (Rac[AUC0-24h]) for Delamanid

Accumulation Ratio for AUC (Rac[AUC]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Accumulation Ratio for Cmax (Rac[Cmax]) for Delamanid

Accumulation Ratio for Cmax (Rac[Cmax]) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for Delamanid

Area Under the Plasma Concentration Curve From 0 to 24 Hours (AUC0-24h) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Cmax 1 and 2: Maximal Peak Concentration (Cmax) for Delamanid Following First and Second Daily Dose

Elimination Half-life (t1/2) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Maximal Peak Concentration (Cmax) for DM-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using the Mycobacteria Growth Indicator Tube (MGIT) System

Time to Maximal Peak Concentration (Tmax) for Delamanid Metabolite (DM)-6704, DM-6705, DM-6706, DM-6717, DM-6718, DM-6720, DM-6721, and DM-6722

Tmax 1 and 2: Time to Maximal Peak Concentration (Tmax) for Delamanid Following First and Second Daily Dose

Area Under the Curve (AUC) of Change From Baseline in Time to Culture Positivity in the MGIT System

Change From Baseline in Time to Culture Positivity Using the MGIT System

Mean Change From Baseline in PR Interval

Mean Change From Baseline in QRS Interval

Mean Change From Baseline in QTcB

Mean Change From Baseline in QTcF

Mean Change From Baseline in QT Interval

Mean Change From Baseline in Ventricular Rate

Percentage of Participants Using Concomitant Medications

Percentage of Participants Who Achieved Final SCC Using MGIT

Percentage of Participants Who Achieved Final SCC Using Solid Culture Media

Percentage of Participants Who Achieved Initial SCC Using the MGIT System

Percentage of Participants Who Achieved Initial SCC Using the Solid Culture Media

Percentage of Participants Who Achieved SCC From the MGIT System Analyzed by Cochran-Armitage Linear Trend Test for Dose-response Relationship

Percentage of Participants Who Achieved Sputum Culture Conversion (SCC) Using Solid Culture Media

Percentage of Participants With At Least One Treatment-Emergent Adverse Events (TEAEs)

Percentage of Participants With Categorical Changes in 12-lead Electrocardiogram Results at Day 56

Percentage of Participants With Change in ECG Morphological Patterns From Baseline

Percentage of Participants With Clinically Significant Audiometry Findings

Percentage of Participants With Clinically Significant Laboratory Test Abnormalities

Percentage of Participants With Clinically Significant Physical Examination Findings, Including Vision and Neuropsychiatric Assessments

Percentage of Participants With Clinically Significant Vital Sign Abnormalities

Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using Solid Culture Media Without Respect to Interim Culture Results

Percentage of Participants With Sputum Culture Negative at Day 57 and Day 84 Using the MGIT System Without Respect to Interim Culture Results

Percentage of Participants With Sputum Culture Negative at Day 57 Using Solid Culture Media Without Respect to Subsequent Culture Results

Percentage of Participants With Sputum Culture Negative at Day 57 Using the MGIT System Without Consideration of Subsequent Culture Results

Time-matched Change From Baseline (Day -1) in QTcF at Day 56