Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis

A Phase 2, Multi-center, Non-controlled, Open-label Dose Escalation Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Orally Administered OPC-67683 Two Times Daily to Patients With Pulmonary Multidrug-Resistant Tuberculosis Refractory to Conventional Treatment

Status

Terminated

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01131351

Enrollment

Registered

2010-05-26

Start date

2010-02-19

Completion date

2011-05-12

Last updated

2021-11-11

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

Conditions

Tuberculosis

Keywords

MDR-TB, Dose Escalation, Phase II, Open Label, Non Controlled, Pulmonary Multidrug-Resistant Tuberculosis (MDR TB)

Brief summary

The purpose of this study is: * To evaluate the safety and tolerability of orally administered OPC-67683 when administered two times daily to MDR tuberculosis (TB) participants refractory to treatment with an optimized background regimen of anti-TB medications (OBR). * To evaluate the pharmacokinetics (PK) of OPC-67683 and metabolites.

Interventions

DRUGDelamanid

OPC-67683 film-coated tablets

DRUGOptimized Background Regimen (OBR)

OBR was selected at the discretion of the study investigator and included at least 2 anti-TB medications based on World Health Organization (WHO's) guidelines for the programmatic management of drug-resistant TB. Study investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.

Study design

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 64 Years

Healthy volunteers

Inclusion criteria

1. Provide written, informed consent prior to all trial-related procedures 2. Male or female participants aged between 18 and 64 years, inclusive. 3. Able to produce sputum for mycobacterium culture or able to obtain sputum produced through Induction. 4. At least three sputum mycobacterium cultures positive for MTB with in-vitro resistance to isoniazid and rifampicin during the previous 270 days (9 months) despite treatment with first and second line anti-TB drugs, including one positive culture within the previous 60 days from the time of sputum collection, prior to date of screening initiation \[defined as the date the informed consent form (ICF) is signed and screening begins\]. 5. Sputum mycobacterial culture positive for MTB with in-vitro susceptibility to at least one anti-TB medication within the previous 60 days prior to the date of screening initiation. 6. Participant judged by the investigator to have potential for clinical benefit from OPC-67683 exposure. 7. 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). 8. Male participant 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

1. A history of allergy to any nitro-imidazoles or nitro-imidazole derivatives at any time. 2. Use of the medications in Section 4.1 including: use of amiodarone at any time during the previous 12 months, use of other antiarrhythmics for the previous 30 days, as well as use of certain antidepressants, anti-histamines, any macrolides, for the previous 14 days. 3. Any current serious concomitant conditions or renal impairment characterized by serum creatinine levels \ 265 micromoles (μmol)/L or hepatic impairment characterized by alanine aminotransferase (ALT) and/or aspartate transferase (AST) levels 3 times the upper limit of the laboratory reference range. 4. Current clinically relevant changes in the Screening electrocardiogram (ECG) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 msec (in both male and female participants), or of the QT interval with Fridericia's correction (QTcF) interval over 450 msec in male participants and over 470 msec in female participants. 5. Current clinically relevant cardiovascular disorder such as heart failure, coronary heart disease, uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction. 6. For participants with human immunodeficiency virus (HIV) infection, helper/inducer T-lymphocyte (CD4 cell) count \< 350/mm\^3 or on treatment with anti-retroviral medication for HIV infection. 7. Karnofsky score \< 50%. 8. Any current diseases or conditions in which the use of nitro-imidazoles or nitro-imidazole derivates is contra-indicated.

Design outcomes

Primary

Measure	Time frame	Description
Rac (AUC): Ratio of Accumulation for AUC of Delamanid	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	Ratio of accumulation for AUC was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Up to approximately 40 weeks	—
Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Up to approximately 40 weeks	—
Percentage of Participants With Adverse Events (AEs)	Up to approximately 40 weeks	An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the investigator.
Percentage of Participants With Immediately Reportable Events (IREs)	Up to approximately 40 weeks	An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-participant hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above. The following were considered as IREs- serious adverse events (SAEs), pregnancies in trial participants or their partners, and all events involving overdose, misuse and abuse.
Cmax: Maximal Peak Plasma Concentration for Delamanid	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	—
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	—
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	AUC0-24h was calculated as 2×AUC0-12h.
Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	Ratio of accumulation for Cmax was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Up to approximately 40 weeks	Vital signs included body weight \[kilogram (kg)\], body temperature \[degree Celsius (°C)\], heart rate \[beats per minute (BPM)\], respiratory rate (breaths/minute), systolic and diastolic blood pressure \[millimeter of mercury (mmHg)\]. The criteria for clinically significant abnormal value were: body weight (kg): increase \>=5% or decrease \>=5%; body temperature (°C): \>=38.5°C and increase of \>=1.1°C; heart rate (BPM): \>=120 bpm and increase of \>=15 bpm, or \<=60 bpm and decrease of \>=15 bpm; systolic blood pressure (mmHg): \>=160 mmHg and increase of \>=20 mmHg, or \<=90 mmHg and decrease of \>=20 mmHg; diastolic blood pressure (mmHg): \>=105 mmHg and increase of \>=15 mmHg, or \<=50 mmHg and decrease of \>=15 mmHg; respiration rate (breaths per minute) \>30 breaths per minute. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.
Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Up to approximately 40 weeks	The criteria for clinically significant abnormal ECG values were- ventricular rate outlier (\<50 bpm and decrease of \>=25%, \>100 bpm and increase of \>=25%), PR outlier \[increase of \>=25% when PR \>200 milliseconds (ms)\], QRS outlier (increase of \>=25% when QRS \>100 ms), QT (new onset (in treatment period but not at Baseline) \[\>500 ms\]), QT interval corrected by Bazett's formula (QTcB) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), QT interval corrected by Fridericia's formula (QTcF) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), new abnormal U waves, new ST segment changes, new T wave changes, new abnormal rhythm, new conduction abnormality were reported as categories. Baseline was defined as the average of the ECGs taken at Day -1. Only categories with data for potentially clinically significant abnormal ECG values are reported.
Percentage of Participants With Potentially Clinically Significant Laboratory Values	Up to approximately 40 weeks	Clinical laboratory tests included hematology, coagulation, chemistry, and urinalysis. The participants were categorized based on the clinically significant laboratory values as per protocol predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported.
Percentage of Participants With Abnormal Audiometry Assessment Values	Up to approximately 40 weeks	—
Percentage of Participants With Abnormal Visual Acuity Assessment Values	Up to approximately 40 weeks	—

Secondary

Measure	Time frame	Description
Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.
AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.
Rac (Cmax): Ratios of Accumulation for Cmax for Delamanid Metabolites	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for Cmax was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.
Rac (AUC): Ratios of Accumulation for AUC for Delamanid Metabolites	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for AUC was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. Limited metabolite exposure on Day 1 did not allow for estimation of Rac for metabolites.
Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168	Day 168 (Week 24)	Sputum culture conversion was evaluated using the MGIT culture system. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.
Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168	Day 168 (Week 24)	Sputum culture status was determined using solid mycobacterial culture media and measuring colony counts per milliliter of sputum. The unit for colony counts: log10 colony-forming unit (CFU)/mL. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.
Mean Change From Baseline in Time to Culture Positivity Using MGIT	Baseline and Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280	The value for time to positivity was defined (in days) as the time interval from inoculation until a positive signal was detected for MTB on sputum culture in the MGIT system during the routine 42 day incubation period. Time to positivity analysis was based on the corresponding qualitative sputum results of positive and negative sputum cultures in days of the initial positive signal for a culture from the MGIT system. Mean is reported for Baseline and mean change from baseline is reported for Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280. Baseline is Day -2 and -1. Mean time to culture positivity at Baseline was defined as the average of Day -2 and Day -1 values, if the cultures on both days were positive; and if only one culture was positive, the value for the positive culture was used as baseline.
Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196	The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.

Countries

Latvia, Lithuania

Participant flow

Recruitment details

Participants took part in the study at 3 investigative sites in Latvia and Lithuania from 19 February 2010 to 12 May 2011.

Pre-assignment details

A total of 10 participants received at least one dose of delamanid (5 participants in delamanid 250 mg BID+ OBR group and 5 participants in delamanid 300 mg BID+ OBR group). Of which, 7 participants completed the study.

Participants by arm

Arm	Count
Delamanid 250 mg BID + OBR Participants received delamanid five 50 mg (250 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.	5
Delamanid 300 mg BID + OBR Participants received delamanid six 50 mg (300 mg) tablets, BID, along with at least 2 additional anti-TB medications per OBR for up to 28 weeks.	5
Total	10

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	0	2
Overall Study	Protocol Deviation	0	1

Baseline characteristics

Characteristic	Delamanid 300 mg BID + OBR	Total	Delamanid 250 mg BID + OBR
Age, Continuous	34.0 years STANDARD_DEVIATION 12.5	40.3 years STANDARD_DEVIATION 12.9	46.6 years STANDARD_DEVIATION 10.8
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants	0 Participants	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants	10 Participants	5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Asian	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Black or African American	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) More than one race	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants	0 Participants	0 Participants
Race (NIH/OMB) White	5 Participants	10 Participants	5 Participants
Sex: Female, Male Female	1 Participants	1 Participants	0 Participants
Sex: Female, Male Male	4 Participants	9 Participants	5 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 5	1 / 5
other Total, other adverse events	5 / 5	5 / 5
serious Total, serious adverse events	2 / 5	2 / 5

Outcome results

Primary

AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid

AUC0-24h was calculated as 2×AUC0-12h.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 28	9840 hournanograms per milliliter (hng/mL)	Standard Deviation 3090
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 56	10500 hournanograms per milliliter (hng/mL)	Standard Deviation 4490
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 112	8020 hournanograms per milliliter (hng/mL)	Standard Deviation 5470
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 1	2020 hournanograms per milliliter (hng/mL)	Standard Deviation 708
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 196	9420 hournanograms per milliliter (hng/mL)	Standard Deviation 2340
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 14	9580 hournanograms per milliliter (hng/mL)	Standard Deviation 2790
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 196	8640 hournanograms per milliliter (hng/mL)	Standard Deviation 2890
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 14	10400 hournanograms per milliliter (hng/mL)	Standard Deviation 1950
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 28	11200 hournanograms per milliliter (hng/mL)	Standard Deviation 2450
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 1	2650 hournanograms per milliliter (hng/mL)	Standard Deviation 1280
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 56	9720 hournanograms per milliliter (hng/mL)	Standard Deviation 2400
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid	Day 112	8470 hournanograms per milliliter (hng/mL)	Standard Deviation 3080

Primary

Cmax: Maximal Peak Plasma Concentration for Delamanid

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: Intent-to-treat (ITT) Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 112	441 nanograms per milliliter (ng/mL)	Standard Deviation 286
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 28	558 nanograms per milliliter (ng/mL)	Standard Deviation 113
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 14	521 nanograms per milliliter (ng/mL)	Standard Deviation 132
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 56	558 nanograms per milliliter (ng/mL)	Standard Deviation 239
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 196	494 nanograms per milliliter (ng/mL)	Standard Deviation 129
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 1	142 nanograms per milliliter (ng/mL)	Standard Deviation 68.2
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 196	499 nanograms per milliliter (ng/mL)	Standard Deviation 241
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 1	192 nanograms per milliliter (ng/mL)	Standard Deviation 93.5
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 56	503 nanograms per milliliter (ng/mL)	Standard Deviation 126
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 112	427 nanograms per milliliter (ng/mL)	Standard Deviation 114
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 14	514 nanograms per milliliter (ng/mL)	Standard Deviation 99.3
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid	Day 28	573 nanograms per milliliter (ng/mL)	Standard Deviation 117

Primary

Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Group	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Total Participants Using One or More Medications	100.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Participants Taking Antibacterials for Systemic Use	80.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Participants Taking Antimycobacterials	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Total Participants Using One or More Medications	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Participants Taking Antibacterials for Systemic Use	80.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial	Participants Taking Antimycobacterials	100.0 percentage of participants

Primary

Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Group	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antidiarrheals, Intestinal Antiinflammatory	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Corticosteroids for Systemic Use	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Agents Acting on the Renin-Angiotensin System	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Cough and Cold Preparations	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antiepileptics	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Digestives, Including Enzymes	80.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Unspecified Herbal and Traditional Medicine	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Diuretics	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antigout Preparations	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Acid Related Disorders	80.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antimycotics for Systemic Use	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Functional Gastrointestinal Disorders	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antihemorrhagics	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Obstructive Airway Diseases	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Analgesics	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Nasal Preparations	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antihypertensives	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Otologicals	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Blood Substitutes and Perfusion Solutions	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Psycholeptics	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antiinflammatory and Antirheumatic Products	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Vasoprotectives	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Cardiac Therapy	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Vitamins	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Total Participants Using One or More Medications	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Vitamins	60.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Total Participants Using One or More Medications	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antihypertensives	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antiinflammatory and Antirheumatic Products	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antimycotics for Systemic Use	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Psycholeptics	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Agents Acting on the Renin-Angiotensin System	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Analgesics	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antidiarrheals, Intestinal Antiinflammatory	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antiepileptics	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antigout Preparations	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Antihemorrhagics	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Blood Substitutes and Perfusion Solutions	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Cardiac Therapy	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Corticosteroids for Systemic Use	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Cough and Cold Preparations	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Digestives, Including Enzymes	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Diuretics	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Acid Related Disorders	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Functional Gastrointestinal Disorders	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Drugs for Obstructive Airway Diseases	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Nasal Preparations	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Otologicals	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Unspecified Herbal and Traditional Medicine	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial	Participants Taking Vasoprotectives	0.0 percentage of participants

Primary

Percentage of Participants With Abnormal Audiometry Assessment Values

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Abnormal Audiometry Assessment Values	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Abnormal Audiometry Assessment Values	80.0 percentage of participants

Primary

Percentage of Participants With Abnormal Visual Acuity Assessment Values

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Abnormal Visual Acuity Assessment Values	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Abnormal Visual Acuity Assessment Values	20.0 percentage of participants

Primary

Percentage of Participants With Adverse Events (AEs)

An AE was defined as any new medical problem, or exacerbation of an existing problem, experienced by a participant while enrolled in the trial, whether or not it was considered drug-related by the investigator.

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Adverse Events (AEs)	100.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Adverse Events (AEs)	100.0 percentage of participants

Primary

Percentage of Participants With Immediately Reportable Events (IREs)

An AE was considered serious if it was fatal; life-threatening; persistently or significantly disabling or incapacitating; required in-participant hospitalization or prolonged hospitalization; a congenital anomaly/birth defect; or other medically significant event that, based upon appropriate medical judgment, may have jeopardized the participant and may have required medical or surgical intervention to prevent one of the outcomes listed above. The following were considered as IREs- serious adverse events (SAEs), pregnancies in trial participants or their partners, and all events involving overdose, misuse and abuse.

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Immediately Reportable Events (IREs)	40.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Immediately Reportable Events (IREs)	40.0 percentage of participants

Primary

Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results

The criteria for clinically significant abnormal ECG values were- ventricular rate outlier (\<50 bpm and decrease of \>=25%, \>100 bpm and increase of \>=25%), PR outlier \[increase of \>=25% when PR \>200 milliseconds (ms)\], QRS outlier (increase of \>=25% when QRS \>100 ms), QT (new onset (in treatment period but not at Baseline) \[\>500 ms\]), QT interval corrected by Bazett's formula (QTcB) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), QT interval corrected by Fridericia's formula (QTcF) (new onset \[\>450, \>480, \>500 ms\], increase of \>=30 ms and \<= 60 ms or increase of \>60 ms), new abnormal U waves, new ST segment changes, new T wave changes, new abnormal rhythm, new conduction abnormality were reported as categories. Baseline was defined as the average of the ECGs taken at Day -1. Only categories with data for potentially clinically significant abnormal ECG values are reported.

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Group	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Vent Rate Outliers: Notable Decreases	40.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Vent Rate Outliers: Notable Increases	40.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>500 msec)	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>480 msec)	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>450 msec)	40.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: Change >=30, <=60 msec	40.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>500 msec)	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>480 msec)	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>450 msec)	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: Change >=30, <=60 msec	60.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	ST Segment: New ST Segment Changes	0.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	T Waves: New T Wave Changes	20.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Rhythm: New Abnormal Rhythm	60.00 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Conduction: New Conduction Changes	0.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	ST Segment: New ST Segment Changes	20.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Vent Rate Outliers: Notable Decreases	0.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>480 msec)	20.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Vent Rate Outliers: Notable Increases	0.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Rhythm: New Abnormal Rhythm	80.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>500 msec)	20.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>450 msec)	40.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>480 msec)	40.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	T Waves: New T Wave Changes	20.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: New Onset (>450 msec)	40.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: Change >=30, <=60 msec	80.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcB: Change >=30, <=60 msec	80.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	Conduction: New Conduction Changes	40.00 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results	QTcF: New Onset (>500 msec)	20.00 percentage of participants

Primary

Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs

Vital signs included body weight \[kilogram (kg)\], body temperature \[degree Celsius (°C)\], heart rate \[beats per minute (BPM)\], respiratory rate (breaths/minute), systolic and diastolic blood pressure \[millimeter of mercury (mmHg)\]. The criteria for clinically significant abnormal value were: body weight (kg): increase \>=5% or decrease \>=5%; body temperature (°C): \>=38.5°C and increase of \>=1.1°C; heart rate (BPM): \>=120 bpm and increase of \>=15 bpm, or \<=60 bpm and decrease of \>=15 bpm; systolic blood pressure (mmHg): \>=160 mmHg and increase of \>=20 mmHg, or \<=90 mmHg and decrease of \>=20 mmHg; diastolic blood pressure (mmHg): \>=105 mmHg and increase of \>=15 mmHg, or \<=50 mmHg and decrease of \>=15 mmHg; respiration rate (breaths per minute) \>30 breaths per minute. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication. Number analyzed is the number of participants who had at least one post-baseline numerical result for the given test. Baseline was defined as the last measurements prior to the first dosing of study medication.

Arm	Measure	Group	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Weight: Decrease of >=5% in Body Weight	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Systolic Blood Pressure: <= 90 mmHg + Decrease of >=20 mmHg	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Weight: Increase of >=5% in Body Weight	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Heart Rate: <=60 bpm + Decrease of >=15 bpm	40.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Respiration Rate: >30 Breaths Per Minute	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Heart Rate: <=60 bpm + Decrease of >=15 bpm	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Weight: Increase of >=5% in Body Weight	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Respiration Rate: >30 Breaths Per Minute	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Systolic Blood Pressure: <= 90 mmHg + Decrease of >=20 mmHg	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs	Weight: Decrease of >=5% in Body Weight	0.0 percentage of participants

Primary

Percentage of Participants With Potentially Clinically Significant Laboratory Values

Clinical laboratory tests included hematology, coagulation, chemistry, and urinalysis. The participants were categorized based on the clinically significant laboratory values as per protocol predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported.

Time frame: Up to approximately 40 weeks

Population: Safety Analysis Population included all participants who received at least one dose (partial dose inclusive) of trial medication.

Arm	Measure	Group	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Uric acid (mg/dL)	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Potassium [milliequivalents per liter (mEq/L)]	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Triglycerides [milligrams per deciliter (mg/dL)]	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Mean Corpuscular Volume [femtoliter (fL)]	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lymphocytes, Absolute [thousand cells per microliter (thous/µL)]	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Sodium (mEq/L)	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Neutrophils, Absolute (thous/µL)	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Platelet Count (thous/µL)	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Reticulocyte Count (%)	60.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Prothrombin Time [seconds (sec)]	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lymphocytes [percentage (%)]	0.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Red Blood Cell Count [million cells per microliter (mill/µL)]	20.0 percentage of participants
Delamanid 250 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lactic Dehydrogenase [units per liter (U/L)]	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Red Blood Cell Count [million cells per microliter (mill/µL)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Sodium (mEq/L)	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Uric acid (mg/dL)	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lymphocytes [percentage (%)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Mean Corpuscular Volume [femtoliter (fL)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Reticulocyte Count (%)	60.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lactic Dehydrogenase [units per liter (U/L)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Triglycerides [milligrams per deciliter (mg/dL)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Lymphocytes, Absolute [thousand cells per microliter (thous/µL)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Neutrophils, Absolute (thous/µL)	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Platelet Count (thous/µL)	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Prothrombin Time [seconds (sec)]	20.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Potentially Clinically Significant Laboratory Values	Potassium [milliequivalents per liter (mEq/L)]	20.0 percentage of participants

Primary

Rac (AUC): Ratio of Accumulation for AUC of Delamanid

Ratio of accumulation for AUC was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 14	4.85 ratio	Standard Deviation 0.938
Delamanid 250 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 56	5.13 ratio	Standard Deviation 0.762
Delamanid 250 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 112	3.74 ratio	Standard Deviation 1.47
Delamanid 250 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 28	4.92 ratio	Standard Deviation 0.699
Delamanid 250 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 196	4.79 ratio	Standard Deviation 0.8
Delamanid 300 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 196	2.29 ratio	Standard Deviation 0.367
Delamanid 300 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 14	5.45 ratio	Standard Deviation 4.38
Delamanid 300 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 28	5.66 ratio	Standard Deviation 4.18
Delamanid 300 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 56	4.55 ratio	Standard Deviation 2.45
Delamanid 300 mg BID + OBR	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 112	2.85 ratio	Standard Deviation 1.27
Unknown	Rac (AUC): Ratio of Accumulation for AUC of Delamanid	Day 1	— ratio	—

Primary

Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid

Ratio of accumulation for Cmax was assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 56	4.04 ratio	Standard Deviation 0.657
Delamanid 250 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 28	4.33 ratio	Standard Deviation 1.31
Delamanid 250 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 112	3.07 ratio	Standard Deviation 1.25
Delamanid 250 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 14	4.01 ratio	Standard Deviation 1.22
Delamanid 250 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 196	3.80 ratio	Standard Deviation 1.25
Delamanid 300 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 196	1.93 ratio	Standard Deviation 0.418
Delamanid 300 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 14	3.76 ratio	Standard Deviation 3.13
Delamanid 300 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 28	4.01 ratio	Standard Deviation 2.84
Delamanid 300 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 56	3.24 ratio	Standard Deviation 1.71
Delamanid 300 mg BID + OBR	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 112	1.89 ratio	Standard Deviation 0.485
Unknown	Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid	Day 1	— ratio	—

Primary

Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEDIAN)
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 1	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 14	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 28	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 56	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 112	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 196	2.95 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 112	3.03 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 1	3.20 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 56	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 14	3.02 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 196	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid	Day 28	3.03 hours

Secondary

AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites

The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 1	45.5 h*ng/mL	Standard Deviation 13.6
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 28	2500 h*ng/mL	Standard Deviation 1110
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 28	1140 h*ng/mL	Standard Deviation 357
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 56	3100 h*ng/mL	Standard Deviation 1480
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 1	11.1 h*ng/mL	—
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 112	2790 h*ng/mL	Standard Deviation 1800
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 56	1280 h*ng/mL	Standard Deviation 499
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 196	3060 h*ng/mL	Standard Deviation 1410
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 112	1630 h*ng/mL	Standard Deviation 815
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 14	966 h*ng/mL	Standard Deviation 531
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 112	1220 h*ng/mL	Standard Deviation 711
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 28	1430 h*ng/mL	Standard Deviation 668
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 14	928 h*ng/mL	Standard Deviation 567
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 56	1670 h*ng/mL	Standard Deviation 608
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 196	1550 h*ng/mL	Standard Deviation 176
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 196	1820 h*ng/mL	Standard Deviation 188
Delamanid 250 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 14	1650 h*ng/mL	Standard Deviation 543
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 196	2060 h*ng/mL	Standard Deviation 2060
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 14	2070 h*ng/mL	Standard Deviation 593
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 112	1760 h*ng/mL	Standard Deviation 1050
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 1	19.2 h*ng/mL	—
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 14	1830 h*ng/mL	Standard Deviation 705
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 28	2100 h*ng/mL	Standard Deviation 666
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 56	2610 h*ng/mL	Standard Deviation 1760
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 112	1820 h*ng/mL	Standard Deviation 1250
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6704: AUC0-24h at Day 196	2130 h*ng/mL	Standard Deviation 2230
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 28	3140 h*ng/mL	Standard Deviation 1140
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 56	3150 h*ng/mL	Standard Deviation 1130
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 112	2710 h*ng/mL	Standard Deviation 1500
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 196	3440 h*ng/mL	Standard Deviation 2890
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 14	1590 h*ng/mL	Standard Deviation 496
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 28	2190 h*ng/mL	Standard Deviation 498
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6706: AUC0-24h at Day 56	2290 h*ng/mL	Standard Deviation 1650
Delamanid 300 mg BID + OBR	AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites	DM-6705: AUC0-24h at Day 1	64.8 h*ng/mL	Standard Deviation 11.5

Secondary

Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites

The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 1	1.33 ng/mL	Standard Deviation 0.257
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 196	71.2 ng/mL	Standard Deviation 8.85
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 14	76.6 ng/mL	Standard Deviation 25.4
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 1	2.88 ng/mL	Standard Deviation 1.41
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 14	43.1 ng/mL	Standard Deviation 25.2
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 196	135 ng/mL	Standard Deviation 62.9
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 56	140 ng/mL	Standard Deviation 64.2
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 14	44.6 ng/mL	Standard Deviation 24.1
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 28	52.5 ng/mL	Standard Deviation 12.8
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 28	64.0 ng/mL	Standard Deviation 27.9
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 28	114 ng/mL	Standard Deviation 47.8
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 56	77.6 ng/mL	Standard Deviation 28.4
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 56	59.9 ng/mL	Standard Deviation 22.4
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 112	75.2 ng/mL	Standard Deviation 36.5
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 112	128 ng/mL	Standard Deviation 85
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 196	81.7 ng/mL	Standard Deviation 6.38
Delamanid 250 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 112	58.5 ng/mL	Standard Deviation 33.8
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 196	94.9 ng/mL	Standard Deviation 92.1
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 14	95.4 ng/mL	Standard Deviation 30.1
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 28	146 ng/mL	Standard Deviation 58.8
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 56	142 ng/mL	Standard Deviation 50.1
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 1	2.53 ng/mL	Standard Deviation 1.59
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 14	82.7 ng/mL	Standard Deviation 32.8
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 28	95.9 ng/mL	Standard Deviation 31.5
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 56	119 ng/mL	Standard Deviation 79.6
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 112	88.8 ng/mL	Standard Deviation 67.3
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Cmax at Day 196	99.3 ng/mL	Standard Deviation 104
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 112	126 ng/mL	Standard Deviation 80.2
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 196	154 ng/mL	Standard Deviation 128
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 14	71.9 ng/mL	Standard Deviation 23.1
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 28	97.7 ng/mL	Standard Deviation 23
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 56	103 ng/mL	Standard Deviation 72.2
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Cmax at Day 112	83.1 ng/mL	Standard Deviation 54.7
Delamanid 300 mg BID + OBR	Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Cmax at Day 1	3.75 ng/mL	Standard Deviation 1.79

Secondary

Mean Change From Baseline in Time to Culture Positivity Using MGIT

The value for time to positivity was defined (in days) as the time interval from inoculation until a positive signal was detected for MTB on sputum culture in the MGIT system during the routine 42 day incubation period. Time to positivity analysis was based on the corresponding qualitative sputum results of positive and negative sputum cultures in days of the initial positive signal for a culture from the MGIT system. Mean is reported for Baseline and mean change from baseline is reported for Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280. Baseline is Day -2 and -1. Mean time to culture positivity at Baseline was defined as the average of Day -2 and Day -1 values, if the cultures on both days were positive; and if only one culture was positive, the value for the positive culture was used as baseline.

Time frame: Baseline and Days 7, 14, 21, 28, 35, 42, 49, 56, 70, 84, 98, 112, 126, 140, 154, 168, 182, 196, 224, 252, and 280

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEAN)	Dispersion
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 84	10.5 days	Standard Deviation 12.4
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 14	0.7 days	Standard Deviation 1
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 42	6.4 days	Standard Deviation 8.7
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 140	1.5 days	Standard Deviation 5.4
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 154	0.8 days	Standard Deviation 2.1
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 196	-0.6 days	Standard Deviation 3.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 224	1.6 days	Standard Deviation 4.6
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 252	9.1 days	Standard Deviation 12
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 280	20.3 days	Standard Deviation 19
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 7	6.8 days	Standard Deviation 12.2
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 21	2.6 days	Standard Deviation 0.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 28	0.9 days	Standard Deviation 2.7
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 35	8.8 days	Standard Deviation 11.1
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 49	0.8 days	Standard Deviation 2.6
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 56	7.3 days	Standard Deviation 11.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 70	7.7 days	Standard Deviation 11.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Baseline	7.7 days	Standard Deviation 3.7
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 98	3.4 days	Standard Deviation 3.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 112	3.8 days	Standard Deviation 7
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 126	-0.8 days	Standard Deviation 2.9
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 168	-0.8 days	Standard Deviation 4.5
Delamanid 250 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 182	-2.5 days	Standard Deviation 3
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 112	10.7 days	Standard Deviation 20
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 28	2.1 days	Standard Deviation 2.5
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 14	1.7 days	Standard Deviation 1.4
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 84	12.1 days	Standard Deviation 16.2
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 35	11.1 days	Standard Deviation 15.1
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 140	17.3 days	Standard Deviation 25.2
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 42	6.3 days	Standard Deviation 9.9
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 154	8.3 days	Standard Deviation 17
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 182	16.5 days	Standard Deviation 24.4
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 168	17.3 days	Standard Deviation 23.2
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 196	20.9 days	Standard Deviation 18.1
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 49	9.1 days	Standard Deviation 16.4
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 224	16.2 days	Standard Deviation 24.8
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 98	9.8 days	Standard Deviation 16.5
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 252	16.5 days	Standard Deviation 24.4
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 56	5.8 days	Standard Deviation 7.6
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 280	16.6 days	Standard Deviation 24.2
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Baseline	6.8 days	Standard Deviation 1.6
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 126	0.1 days	Standard Deviation 1.9
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 7	3.5 days	Standard Deviation 2.9
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 70	16.4 days	Standard Deviation 16.9
Delamanid 300 mg BID + OBR	Mean Change From Baseline in Time to Culture Positivity Using MGIT	Change from Baseline at Day 21	2.1 days	Standard Deviation 2

Secondary

Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168

Sputum culture conversion was evaluated using the MGIT culture system. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.

Time frame: Day 168 (Week 24)

Population: ITT Population included all participants who took at least one dose of IMP.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168	20.0 percentage of participants

Secondary

Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168

Sputum culture status was determined using solid mycobacterial culture media and measuring colony counts per milliliter of sputum. The unit for colony counts: log10 colony-forming unit (CFU)/mL. A participant was classified as demonstrating a sputum culture conversion if he/she achieved two consecutive sputum cultures negative for growth of Mycobacterium tuberculosis at least 28 days apart after his/her last sputum culture positive for growth and not followed by any sputum specimens positive for growth.

Time frame: Day 168 (Week 24)

Population: ITT Population included all participants who took at least one dose of IMP.

Arm	Measure	Value (NUMBER)
Delamanid 250 mg BID + OBR	Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168	0.0 percentage of participants
Delamanid 300 mg BID + OBR	Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168	20.0 percentage of participants

Secondary

Rac (AUC): Ratios of Accumulation for AUC for Delamanid Metabolites

The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for AUC was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1. Limited metabolite exposure on Day 1 did not allow for estimation of Rac for metabolites.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint.

Secondary

Rac (Cmax): Ratios of Accumulation for Cmax for Delamanid Metabolites

The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706. Ratio of accumulation for Cmax was planned to be assessed on Days 14, 28, 56, 112 and 196 with respect to Day 1.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: Due to limited metabolite exposure on Day 1, the Rac for metabolites was not estimated and hence data was not collected for this endpoint.

Secondary

Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites

The primary metabolites of delamanid are DM-6704, DM-6705 and DM-6706.

Time frame: At 24 hours post dose on Days 1, 14, 28, 56, 112 and 196

Population: ITT Population included all participants who took at least one dose of IMP. Number analyzed is the number of participants with evaluable data at the given time point.

Arm	Measure	Group	Value (MEDIAN)
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 28	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 28	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 1	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 56	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 112	0.00 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 112	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 14	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 196	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 56	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 14	8.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 196	8.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 28	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 1	11.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 56	5.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 196	2.95 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 112	0.00 hours
Delamanid 250 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 14	2.95 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 196	6.01 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 28	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 56	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 112	0.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 196	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 1	5.92 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 112	0.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 1	12.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 14	9.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 28	6.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 56	8.97 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 112	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6705: Tmax at Day 196	7.49 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 14	0.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 28	3.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6706: Tmax at Day 56	0.00 hours
Delamanid 300 mg BID + OBR	Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites	DM-6704: Tmax at Day 14	3.02 hours

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026

Safety and Pharmacokinetics (PK) in Multidrug-Resistant (MDR) Refractive Tuberculosis

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AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid

Cmax: Maximal Peak Plasma Concentration for Delamanid

Percentage of Participants Taking Concomitant Anti-Tuberculosis (TB) Medication During the Trial

Percentage of Participants Taking Concomitant (Excluding Anti-TB) Medication During the Trial

Percentage of Participants With Abnormal Audiometry Assessment Values

Percentage of Participants With Abnormal Visual Acuity Assessment Values

Percentage of Participants With Adverse Events (AEs)

Percentage of Participants With Immediately Reportable Events (IREs)

Percentage of Participants With Potentially Clinically Significant Abnormalities in Electrocardiogram (ECG) Results

Percentage of Participants With Potentially Clinically Significant Abnormalities in Vital Signs

Percentage of Participants With Potentially Clinically Significant Laboratory Values

Rac (AUC): Ratio of Accumulation for AUC of Delamanid

Rac (Cmax): Ratio of Accumulation for Cmax of Delamanid

Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid

AUC0-24h: Area Under the Plasma Concentration-Time Curve From 0 To 24 Hours for Delamanid Metabolites

Cmax: Maximal Peak Plasma Concentration for Delamanid Metabolites

Mean Change From Baseline in Time to Culture Positivity Using MGIT

Percentage of Participants With Sputum Culture Conversion by Mycobacteria Growth Indicator Tube (MGIT) at Day 168

Percentage of Participants With Sputum Culture Conversion on Solid Mycobacterial Culture Media at Day 168

Rac (AUC): Ratios of Accumulation for AUC for Delamanid Metabolites

Rac (Cmax): Ratios of Accumulation for Cmax for Delamanid Metabolites

Tmax: Time to Reach Maximal Peak Plasma Concentration for Delamanid Metabolites