A Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683

• Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02573350
• Collaborator: (none)
• Enrollment: 213
• Locations: 8
• Arms: 2
• Actual Duration (Months): 31
• Patients Per Site: 26.6
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

A phase 2, multicenter, uncontrolled, open-label trial in participants with Multi-drug Resistant Tuberculosis (MDR-TB). Only participants who completed Trial 242-07-204 (NCT00685360) were eligible. The trial was performed globally at 14 sites qualified to treat MDR-TB. All 434 participants who completed Trial 242-07-204 were eligible for this trial if there was still potential clinical benefit to them and all inclusion criteria and no exclusion criteria were met.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis, Multidrug-Resistant	Drug: Delamanid; Drug: OBR	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 213 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Multi-center, Uncontrolled, Open-label Trial to Evaluate Safety, Tolerability, and Efficacy of Orally Administered OPC-67683 as 100 mg BID With Optional Titration to 200 mg BID for up to Six Months Exposure in Patients With Pulmonary Multi-drug Resistant Tuberculosis
• Actual Study Start Date: Mar 26, 2009
• Actual Primary Completion Date: Oct 27, 2011
• Actual Study Completion Date: Oct 27, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Delamanid 100 mg BID + OBR Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Drug: Delamanid; Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening.; Other Names: OPC-67683 Deltyba ; Drug: 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. Study investigators could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Experimental: Delamanid 200 mg BID + OBR Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.	Drug: Delamanid; Delamanid was administered orally twice daily as 50-mg tablets under fed conditions in the morning and evening.; Other Names: OPC-67683 Deltyba ; Drug: 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. Study investigators could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Clinically Significant Abnormality in Vital Signs [From first dose of study drug up to Week 26]

   Vital signs included weight (kg), body temperature (degree Celsius), heart rate [beats/minute (bpm)], systolic and diastolic blood pressure [millimetre of mercury (mm Hg)]. The criteria for clinically significant abnormal value for: weight was decrease or increase of >=5% in body weight, heart rate was <=60 bpm and decrease of >=15 bpm; >=120 bpm and Increase of >=15 bpm, systolic blood pressure (SBP) <=90 mm Hg and decrease of >=20 mm Hg; diastolic blood pressure (DBP) <=50 mm Hg and decrease of >=15 mm Hg, all vital signs relative to Baseline. Baseline is Study 204 completion visit (Day 84) for participants who complete the baseline visit within 7 days of completing Study 204. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.

2. Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values [From first dose of study drug up to Week 26]

   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. Only categories with data are reported.

3. Number of Participants With Clinical Significant Abnormality in Laboratory Test [From first dose of study drug up to Week 26]

   Laboratory assessments included parameters for serum chemistry (alkaline phosphatase, alanine aminotransferase, alanine transaminase, total bilirubin, cholesterol, gamma-glutamyl transferase, glucose, lactic dehydrogenase, potassium, sodium, triglycerides, uric acid), hematology (white blood cell count eosinophils, absolute, hematocrit, hemoglobin, lymphocytes, absolute, mean corpuscular volume, neutrophil, bands, neutrophils, neutrophils, absolute, platelet count, red blood cell (RBC) count, reticulocyte count) and urinalysis (blood, epithelial cast, granular cast, hyaline cast, RBCs per high power field (RBC/HPF)). The participants were categorized based on the clinically significant laboratory values as per predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported.

4. Number of Participants With Abnormality in Audiometry at Baseline [Baseline]

   Audiometry assessments were done at Baseline.

5. Number of Participants With Abnormality in Visual Acuity [From first dose of study drug up to Week 26]

6. Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE) [From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)]

   Participants with abnormal neurological and psychiatric assessments were reported. An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug.

7. Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE [From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)]

   Participants with abnormal thyroid free T4 nanograms per deciliter (ng/dL) and thyroid-stimulating hormone (>=3 OR <=0.3 micro-international units per litre (uIU/mL). An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug.

8. Number of Participants With Any Concomitant Medication Usage [From first dose of study drug up to Week 26]

   Concomitant medications are defined as medications that started on or after the first day of study treatment or were started prior to study treatment but were ongoing on the first day of study treatment.

9. Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs) [From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)]

   An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. An SAE is an AE that resulted in death, inpatient hospitalization/prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event.

10. Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE [From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)]

    Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported.

11. Number of Participants With Clinical Significant Abnormality in Cortisol [From first dose of study drug up to Week 26]

    Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported.

Secondary Outcome Measures

1. Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System [Week 26]

   Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with sputum culture conversion (SCC) at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis (MTB) at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).

2. Percentage of Treatment Responders Using Solid Culture Medium [Week 26]

   Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with SCC at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of MTB at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion)

3. Percentage of Treatment Non-responders Using the MGIT Culture System [Week 26]

   Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. The total percentage of treatment non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion)

4. Percentage of Treatment Non-responders Using Solid Culture Medium [Week 26]

   Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. Treatment Non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the Solid culture medium (ie, sputum culture conversion).

5. Percentage of Sustained Converters Using the MGIT Culture System [Week 26]

   The total percentage of sustained converters was defined as the percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion)

6. Percentage of Sustained Converters Using Solid Culture Medium [Week 26]

   The total percentage of sustained converters was defined as percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Determined by Solid culture medium. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion)

7. Percentage of New Converters Using the MGIT Culture System [Week 26]

   The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).

8. Percentage of New Converters Using Solid Culture Medium [Week 26]

   The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).

9. Percentage of Non-converters Using the MGIT Culture System [Week 26]

   The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).

10. Percentage of Non-converters Using Solid Culture Medium [Week 26]

    The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).

11. Percentage of Reverters Using the MGIT Culture System [Week 26]

    The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).

12. Percentage of Reverters Using Solid Culture Medium [Week 26]

    The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).

13. Percentage of Participants Who Developed Resistance to Delamanid While on Treatment [Up to Week 26]

    Resistance was defined as mycobacterium tuberculosis (MTB) growth on the delamanid-containing medium of greater than 1% of that on the drug-free medium. The overall resistance to delamanid during the study was assessed.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 64 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Provide written, informed consent prior to all trial-related procedures

• Male or female participants aged between 18 and 64 years, inclusive, at the time of enrollment into the 242-07-204 trial. Participants who were 64 years at the time of 204 enrollment and who are now 65 years, are eligible for this trial.

• Participants who have completed trial 242-07-204

• Participants judged by the investigator to have the potential for clinical benefit from OPC-67683 exposure

• Able to produce sputum for mycobacterial culture or able to obtain sputum produced through induction

• Female participants of childbearing potential must have a negative urine pregnancy test and agree to use a highly effective method of birth control throughout the participation in the trial and for 22 weeks after last dose.

• 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.

Exclusion Criteria:

• Greater than 30 days has elapsed from the participant's date of completion in the 242-07-204 trial or greater than 30 days has elapsed since the patient's trial investigator's site was initiated in this trial, whichever is later.

• A history of allergy to any nitro-imidazoles or nitro-imidazole derivates at any time.

• Use of the medications in Section 5.4.7 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 moles per liter (mol/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 from the screening lab results.

• Current clinically relevant changes in the electrocardiogram (ECG) (between Trial 242-07-204 Day 56 assessment and baseline) such as any atrioventricular (AV) block, prolongation of the QRS complex over 120 milliseconds (msec) (in both male and female participants), or the corrected QT interval using Fridericia's method (QTcF) interval over 450 msec in male participants and 470 msec in female participants.

• Current clinically relevant cardiovascular disorders such as heart failure, coronary artery disease, uncontrolled or poorly controlled hypertension, arrhythmia, tachyarrhythmia or status after myocardial infarction.

• Any participants with known or reported significant psychiatric history.

• For participants with human immunodeficiency virus (HIV) infection, CD4 cell count less than 350/cubic millimeter (mm^3) or on treatment with antiretroviral medication for HIV infection.

• Karnofsky score under 50 percent (%) while hospitalized and less than 60% while not hospitalized.

• Any current 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 participants in the opinion of the investigator.

• Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than OPC-67683 given as IMP in trial 242-07-204.

• 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/methamphetamine, tetrahydrocannabinol, barbiturates, and opiates as determined by a urine drug screen, unless evidence is provided that the positive drug screen is the result of authorized medications or 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Beijing Chest Hospital	Beijing		China	101149
2	North Estonian Medical Centre Foundation Center of Pulmonology	Tallinn		Estonia	13419
3	Tartu University Lung Hospital	Tartu		Estonia	51014
4	Younsei University Medical Center	Seoul		Korea, Republic of	120-752
5	Asan Medical Center	Seoul		Korea, Republic of	138-736
6	State Agency of Tuberculosis and Lung Disease	Riga		Latvia	LV2118
7	Hospital Nacional Sergio E. Bernales	Lima		Peru	41
8	Tropical Disease Foundation	Makati City		Philippines	1229

Sponsors and Collaborators

• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
• ClinicalTrials.gov Identifier: NCT02573350
• Other Study ID Numbers: 242-07-208; 2008-005107-26
• First Posted: Oct 9, 2015
• Last Update Posted: Nov 1, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Tuberculosis; Tuberculosis, Multidrug-Resistant

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 14 investigative sites in the Philippines, Latvia, Estonia, South Korea, Peru, China, and Japan from 26 March 2009 to 27 October 2011.
Pre-assignment Detail	The study consisted of a Pre-treatment, Treatment, and Follow-up Period. The Pre-treatment Period consisted of a screening and baseline visit. This was followed by a 26-week Treatment Period. There was also a Follow-up Period (28 to 32 days) for the collection of Adverse events (AEs).

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on World Health Organization (WHO) guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Period Title: Overall Study
STARTED	137	76
Efficacy Analysis Population	132	73
Safety Population	137	76
COMPLETED	121	67
NOT COMPLETED	16	9

Baseline Characteristics

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR	Total
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.	Total of all reporting groups
Overall Participants	137	76	213
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	36.8 (12.36)	37.1 (10.98)	36.9 (11.86)
Sex: Female, Male (Count of Participants)
Female	41 29.9%	21 27.6%	62 29.1%
Male	96 70.1%	55 72.4%	151 70.9%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	22 16.1%	17 22.4%	39 18.3%
Not Hispanic or Latino	115 83.9%	59 77.6%	174 81.7%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	100 73%	24 31.6%	124 58.2%
White	16 11.7%	34 44.7%	50 23.5%
Other	21 15.3%	18 23.7%	39 18.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormality in Vital Signs
Description	Vital signs included weight (kg), body temperature (degree Celsius), heart rate [beats/minute (bpm)], systolic and diastolic blood pressure [millimetre of mercury (mm Hg)]. The criteria for clinically significant abnormal value for: weight was decrease or increase of >=5% in body weight, heart rate was <=60 bpm and decrease of >=15 bpm; >=120 bpm and Increase of >=15 bpm, systolic blood pressure (SBP) <=90 mm Hg and decrease of >=20 mm Hg; diastolic blood pressure (DBP) <=50 mm Hg and decrease of >=15 mm Hg, all vital signs relative to Baseline. Baseline is Study 204 completion visit (Day 84) for participants who complete the baseline visit within 7 days of completing Study 204. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with data available for analyses at the given time point.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Weight Decrease of >=5%	23 16.8%	11 14.5%
Weight Increase of >=5%	34 24.8%	25 32.9%
Heart Rate: <=60 bpm and Decrease of >=15 bpm	10 7.3%	11 14.5%
Heart Rate: >=120 bpm and Increase of >=15 bpm	1 0.7%	0 0%
SBP: <=90 mm Hg and Decrease of >=20 mm Hg	16 11.7%	2 2.6%
SBP: >=160 mm Hg and Increase of >=20 mm Hg	3 2.2%	0 0%
DBP: <=50 mm Hg and Decrease of >=15 mm Hg	1 0.7%	2 2.6%

2. Primary Outcome

Title	Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
Description	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. Only categories with data are reported.
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
QRS Outlier	2 1.5%	0 0%
QT Interval, New Onset (>500 msec)	1 0.7%	0 0%
QTcB Interval, New Onset (>450 msec)	62 45.3%	37 48.7%
QTcB Interval, New Onset (>480 msec)	11 8%	7 9.2%
QTcB Interval, New Onset (>500 msec)	2 1.5%	3 3.9%
QTcB Interval, Increase from Baseline >=30 msec and <=60 msec	58 42.3%	39 51.3%
QTcB Interval, Increase from Baseline >60 msec	5 3.6%	7 9.2%
QTcF Interval, New Onset (>450 msec)	23 16.8%	10 13.2%
QTcF Interval, New Onset (>480 msec)	3 2.2%	1 1.3%
QTcF Interval, New Onset (>500 msec)	1 0.7%	1 1.3%
QTcF Interval, Increase from Baseline >=30 msec and <=60 msec	36 26.3%	30 39.5%
QTcF Interval, Increase from Baseline >60 msec	4 2.9%	4 5.3%
Ventricular Rate Notable Changes, <50 bpm and Decrease from Baseline of >=25%	1 0.7%	2 2.6%
Ventricular Rate Notable Changes, >100 bpm and Increase from Baseline of >=25%	16 11.7%	8 10.5%
New Abnormal U Waves	4 2.9%	0 0%
New ST Segment Changes	11 8%	2 2.6%
New T Waves Changes	27 19.7%	14 18.4%
New Abnormal Rhythm	44 32.1%	22 28.9%
New Conduction	10 7.3%	4 5.3%

3. Primary Outcome

Title	Number of Participants With Clinical Significant Abnormality in Laboratory Test
Description	Laboratory assessments included parameters for serum chemistry (alkaline phosphatase, alanine aminotransferase, alanine transaminase, total bilirubin, cholesterol, gamma-glutamyl transferase, glucose, lactic dehydrogenase, potassium, sodium, triglycerides, uric acid), hematology (white blood cell count eosinophils, absolute, hematocrit, hemoglobin, lymphocytes, absolute, mean corpuscular volume, neutrophil, bands, neutrophils, neutrophils, absolute, platelet count, red blood cell (RBC) count, reticulocyte count) and urinalysis (blood, epithelial cast, granular cast, hyaline cast, RBCs per high power field (RBC/HPF)). The participants were categorized based on the clinically significant laboratory values as per predefined criteria. The categories with at least one participant with clinically significant value outside the normal range for laboratory assessments are reported.
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with at least one post-baseline result for the given test.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received delamanid 200 mg (4x50 mg tablets), orally, BID plus OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant may have been titrated to delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of delamanid dose administered during the study.
Measure Participants	137	76
Alkaline Phosphatase	0 0%	1 1.3%
Alanine Aminotransferase (SGPT)	2 1.5%	1 1.3%
Aspartate Aminotransferase (SGOT)	2 1.5%	1 1.3%
Total Bilirubin	7 5.1%	4 5.3%
Cholesterol	1 0.7%	2 2.6%
GAMMA-Glutamyl Transferase	2 1.5%	2 2.6%
Glucose	5 3.6%	3 3.9%
Lactic Dehydrogenase	22 16.1%	5 6.6%
Potassium	13 9.5%	10 13.2%
Sodium	16 11.7%	16 21.1%
Triglycerides	9 6.6%	3 3.9%
Uric Acid	9 6.6%	8 10.5%
Eosinophils, Absolute	10 7.3%	3 3.9%
Hematocrit	2 1.5%	4 5.3%
Hemoglobin	61 44.5%	24 31.6%
Lymphocytes, Absolute	0 0%	1 1.3%
Mean Corpuscular Volume	20 14.6%	13 17.1%
Neutrophil, Bands	0 0%	1 1.3%
Neutrophils	6 4.4%	2 2.6%
Neutrophils, Absolute	17 12.4%	10 13.2%
Platelet Count	5 3.6%	3 3.9%
Red Blood Cell Count	15 10.9%	14 18.4%
Reticulocyte Count	9 6.6%	5 6.6%
White Blood Count	6 4.4%	3 3.9%
Blood Urine Present	41 29.9%	29 38.2%
Epithelial Cast in Urine	1 0.7%	1 1.3%
Granular Cast in Urine	9 6.6%	3 3.9%
Hyaline Cast in Urine	6 4.4%	6 7.9%
RBC/HPF in Urine	13 9.5%	5 6.6%

4. Primary Outcome

Title	Number of Participants With Abnormality in Audiometry at Baseline
Description	Audiometry assessments were done at Baseline.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Count of Participants [Participants]	90 65.7%	34 44.7%

5. Primary Outcome

Title	Number of Participants With Abnormality in Visual Acuity
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Count of Participants [Participants]	45 32.8%	35 46.1%

6. Primary Outcome

Title	Number of Participants With Abnormality in Neurological and Psychiatric Assessment Reported as Treatment-emergent Adverse Event (TEAE)
Description	Participants with abnormal neurological and psychiatric assessments were reported. An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug.
Time Frame	From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Neurological Disorders	63 46%	25 32.9%
Psychiatric Disorders	44 32.1%	38 50%

7. Primary Outcome

Title	Number of Participants With Clinical Significant Abnormality in Thyroid Function Test Reported as TEAE
Description	Participants with abnormal thyroid free T4 nanograms per deciliter (ng/dL) and thyroid-stimulating hormone (>=3 OR <=0.3 micro-international units per litre (uIU/mL). An AE is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug.
Time Frame	From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100mg BID + OBR	Delamanid 200mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Count of Participants [Participants]	0 0%	1 1.3%

8. Primary Outcome

Title	Number of Participants With Any Concomitant Medication Usage
Description	Concomitant medications are defined as medications that started on or after the first day of study treatment or were started prior to study treatment but were ongoing on the first day of study treatment.
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Count of Participants [Participants]	135 98.5%	75 98.7%

9. Primary Outcome

Title	Percentage of Participants With At Least One TEAEs and Serious Adverse Events (SAEs)
Description	An adverse event (AE) is any untoward medical occurrence in a participant/clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with treatment. A TEAE is any new AE or worsening of an existing condition after initiation of study drug. An SAE is an AE that resulted in death, inpatient hospitalization/prolongation of existing hospitalization, persistent or significant disability or incapacity, life-threatening, a congenital anomaly/birth defect, or an important medical event.
Time Frame	From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
TEAEs	92.0 67.2%	97.4 128.2%
SAEs	13.9 10.1%	7.9 10.4%

10. Primary Outcome

Title	Number of Participants With Clinical Significant Abnormality in Coagulation (PT and aPTT) Reported as TEAE
Description	Participants with clinically significant abnormal coagulation (prothrombin time (PT) >17.5 seconds and activated partial thromboplastin time (aPTT) >45 seconds) were reported.
Time Frame	From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study. Number analyzed is the number of participants with at least one post-baseline result for the given test.

Arm/Group Title	Delamanid 100mg BID + OBR	Delamanid 200mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	137	76
Activated Partial Thromboplastin Time	12 8.8%	8 10.5%
Prothrombin Time	2 1.5%	1 1.3%

11. Primary Outcome

Title	Number of Participants With Clinical Significant Abnormality in Cortisol
Description	Participants with clinically significant cortisol >=26 micrograms/decilitre (ug/dL) were reported.
Time Frame	From first dose of study drug up to Week 26

Outcome Measure Data

Analysis Population Description

Safety Population included all participants treated with at least one dose of Delamanid in this study. Overall number of participants analyzed is the number of participants with at least one post-baseline result for the given test.

Arm/Group Title	Delamanid 100mg BID + OBR	Delamanid 200mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	136	76
Count of Participants [Participants]	44 32.1%	19 25%

12. Secondary Outcome

Title	Percentage of Treatment Responders Using the Mycobacterial Growth Indicator Tube (MGIT) Culture System
Description	Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with sputum culture conversion (SCC) at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of mycobacterium tuberculosis (MTB) at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	79.5 58%	75.3 99.1%

13. Secondary Outcome

Title	Percentage of Treatment Responders Using Solid Culture Medium
Description	Treatment Responder was defined as a participant classified as sustained converter or a new converter. Sustained Converter was defined as a participant with SCC at baseline and without any positive culture result during the 26-week trial period. New converter was defined as a participant without SCC at baseline who subsequently met the definition of SCC. A participant was classified as having achieved SCC if he/she achieved 2 consecutive sputum cultures negative for growth of MTB at least 28 days apart after his/her last sputum culture that was positive for growth. The total percentage of treatment responders was calculated as the number of sustained converters plus the number of new converters divided by the total number of participants in the analysis population. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	81.8 59.7%	82.2 108.2%

14. Secondary Outcome

Title	Percentage of Treatment Non-responders Using the MGIT Culture System
Description	Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. The total percentage of treatment non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	20.5 15%	24.7 32.5%

15. Secondary Outcome

Title	Percentage of Treatment Non-responders Using Solid Culture Medium
Description	Non-responders were defined as participants classified as non-converter or reverter. Non-converters were defined as participants without SCC at baseline and who did not achieve SCC during the 26-week trial period whereas reverters were participants with SCC at baseline and at least one positive post-baseline result. Treatment Non-responders was calculated as the number of reverters plus the number of non-converters divided by the total number of participants in the analysis population. Efficacy was assessed by the Solid culture medium (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	18.2 13.3%	17.8 23.4%

16. Secondary Outcome

Title	Percentage of Sustained Converters Using the MGIT Culture System
Description	The total percentage of sustained converters was defined as the percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	69.7 50.9%	69.9 92%

17. Secondary Outcome

Title	Percentage of Sustained Converters Using Solid Culture Medium
Description	The total percentage of sustained converters was defined as percentage of participants in the analysis dataset who had SCC at baseline and non-positive sputum culture results for all post-baseline visits. Determined by Solid culture medium. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion)
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	74.2 54.2%	72.6 95.5%

18. Secondary Outcome

Title	Percentage of New Converters Using the MGIT Culture System
Description	The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	9.8 7.2%	5.5 7.2%

19. Secondary Outcome

Title	Percentage of New Converters Using Solid Culture Medium
Description	The total percentage of new converters was defined as the percentage of participants in the analysis dataset without SCC at baseline who achieved SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	7.6 5.5%	9.6 12.6%

20. Secondary Outcome

Title	Percentage of Non-converters Using the MGIT Culture System
Description	The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	8.3 6.1%	13.7 18%

21. Secondary Outcome

Title	Percentage of Non-converters Using Solid Culture Medium
Description	The total percentage of non-converters was defined as the percentage of participants in the analysis dataset without SCC at baseline and who did not achieve SCC during the 26-week trial period. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	6.8 5%	9.6 12.6%

22. Secondary Outcome

Title	Percentage of Reverters Using the MGIT Culture System
Description	The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the MGIT sputum culture system (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	12.1 8.8%	11.0 14.5%

23. Secondary Outcome

Title	Percentage of Reverters Using Solid Culture Medium
Description	The total percentage of reverters was defined as the percentage of participants in the analysis dataset with SCC at baseline and at least one positive post-baseline result. Efficacy was assessed by the solid culture medium (ie, sputum culture conversion).
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number (95% Confidence Interval) [percentage of participants]	11.4 8.3%	8.2 10.8%

24. Secondary Outcome

Title	Percentage of Participants Who Developed Resistance to Delamanid While on Treatment
Description	Resistance was defined as mycobacterium tuberculosis (MTB) growth on the delamanid-containing medium of greater than 1% of that on the drug-free medium. The overall resistance to delamanid during the study was assessed.
Time Frame	Up to Week 26

Outcome Measure Data

Analysis Population Description

Efficacy Analysis Population included all enrolled participants who had a baseline and a post-baseline measurement available for assessment of any efficacy endpoint.

Arm/Group Title	Delamanid 100 mg BID + OBR	Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 mg (2x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.	Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
Measure Participants	132	73
Number [percentage of participants]	1.5 1.1%	2.7 3.6%

Adverse Events

Time Frame	From first dose through 28 days after last dose of study drug (up to approximately 30 weeks)
Adverse Event Reporting Description	Safety Population included all participants treated with at least one dose of Delamanid in this study.
Arm/Group Title	Delamanid 100 mg BID + OBR		Delamanid 200 mg BID + OBR
Arm/Group Description	Participants received Delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) along with at least 4 additional anti-TB medications per optimized background regimen (OBR) from Week 0 to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment.		Participants received Delamanid 200 mg (4x50 mg tablets), orally, BID along with at least 4 additional anti-TB medications per OBR up to Week 26. Participants were administered OBR as directed by the given investigator based on WHO guidelines and clinical judgment. A participant might have been titrated to Delamanid 200 mg BID after an initial hospitalization of 2 weeks. Participants were grouped according to the longest duration of Delamanid dose administered during the study.
All Cause Mortality
	Delamanid 100 mg BID + OBR		Delamanid 200 mg BID + OBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/137 (0.7%)		0/76 (0%)
Serious Adverse Events
	Delamanid 100 mg BID + OBR		Delamanid 200 mg BID + OBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	19/137 (13.9%)		6/76 (7.9%)
Cardiac disorders
Right ventricular failure	1/137 (0.7%)		0/76 (0%)
Hepatobiliary disorders
Hepatitis acute	0/137 (0%)		1/76 (1.3%)
Hyperbilirubinaemia	2/137 (1.5%)		1/76 (1.3%)
Infections and infestations
Appendicitis	1/137 (0.7%)		0/76 (0%)
Lung infection	1/137 (0.7%)		0/76 (0%)
Pulmonary tuberculoma	1/137 (0.7%)		0/76 (0%)
Tuberculosis	2/137 (1.5%)		1/76 (1.3%)
Injury, poisoning and procedural complications
Gun shot wound	1/137 (0.7%)		0/76 (0%)
Intentional overdose	0/137 (0%)		1/76 (1.3%)
Investigations
Blood pressure increased	1/137 (0.7%)		0/76 (0%)
Electrocardiogram Qt prolonged	1/137 (0.7%)		1/76 (1.3%)
Transaminases increased	1/137 (0.7%)		0/76 (0%)
Metabolism and nutrition disorders
Hypokalaemia	1/137 (0.7%)		0/76 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip and/or oral cavity cancer	0/137 (0%)		1/76 (1.3%)
Nervous system disorders
Headache	1/137 (0.7%)		0/76 (0%)
Polyneuropathy	1/137 (0.7%)		0/76 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion incomplete	1/137 (0.7%)		0/76 (0%)
Psychiatric disorders
Suicidal ideation	1/137 (0.7%)		0/76 (0%)
Suicide attempt	0/137 (0%)		1/76 (1.3%)
Respiratory, thoracic and mediastinal disorders
Dyspnoea	1/137 (0.7%)		0/76 (0%)
Haemoptysis	2/137 (1.5%)		0/76 (0%)
Hydropneumothorax	1/137 (0.7%)		0/76 (0%)
Respiratory failure	1/137 (0.7%)		0/76 (0%)
Other (Not Including Serious) Adverse Events
	Delamanid 100 mg BID + OBR		Delamanid 200 mg BID + OBR
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	126/137 (92%)		73/76 (96.1%)
Cardiac disorders
Palpitations	18/137 (13.1%)		0/76 (0%)
Ear and labyrinth disorders
Tinnitus	16/137 (11.7%)		5/76 (6.6%)
Gastrointestinal disorders
Abdominal pain	8/137 (5.8%)		1/76 (1.3%)
Abdominal pain lower	7/137 (5.1%)		1/76 (1.3%)
Abdominal pain upper	19/137 (13.9%)		6/76 (7.9%)
Diarrhoea	14/137 (10.2%)		7/76 (9.2%)
Dyspepsia	7/137 (5.1%)		6/76 (7.9%)
Gastritis	10/137 (7.3%)		8/76 (10.5%)
Nausea	20/137 (14.6%)		15/76 (19.7%)
Toothache	8/137 (5.8%)		6/76 (7.9%)
Vomiting	24/137 (17.5%)		5/76 (6.6%)
General disorders
Chest pain	12/137 (8.8%)		6/76 (7.9%)
Hepatobiliary disorders
Hyperbilirubinaemia	8/137 (5.8%)		1/76 (1.3%)
Infections and infestations
Folliculitis	1/137 (0.7%)		4/76 (5.3%)
Lung infection	7/137 (5.1%)		2/76 (2.6%)
Nasopharyngitis	12/137 (8.8%)		12/76 (15.8%)
Pharyngitis	6/137 (4.4%)		4/76 (5.3%)
Tracheobronchitis	2/137 (1.5%)		4/76 (5.3%)
Upper respiratory tract infection	11/137 (8%)		5/76 (6.6%)
Investigations
Blood cortisol increased	12/137 (8.8%)		1/76 (1.3%)
Metabolism and nutrition disorders
Decreased appetite	11/137 (8%)		3/76 (3.9%)
Hyperuricaemia	11/137 (8%)		3/76 (3.9%)
Hypokalaemia	11/137 (8%)		0/76 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	21/137 (15.3%)		8/76 (10.5%)
Back pain	8/137 (5.8%)		5/76 (6.6%)
Myalgia	15/137 (10.9%)		2/76 (2.6%)
Nervous system disorders
Dizziness	19/137 (13.9%)		3/76 (3.9%)
Headache	42/137 (30.7%)		12/76 (15.8%)
Paraesthesia	8/137 (5.8%)		5/76 (6.6%)
Somnolence	14/137 (10.2%)		4/76 (5.3%)
Tremor	9/137 (6.6%)		0/76 (0%)
Psychiatric disorders
Alcohol abuse	1/137 (0.7%)		7/76 (9.2%)
Anxiety	6/137 (4.4%)		7/76 (9.2%)
Depression	4/137 (2.9%)		4/76 (5.3%)
Insomnia	30/137 (21.9%)		20/76 (26.3%)
Respiratory, thoracic and mediastinal disorders
Cough	5/137 (3.6%)		5/76 (6.6%)
Haemoptysis	8/137 (5.8%)		3/76 (3.9%)
Throat irritation	9/137 (6.6%)		1/76 (1.3%)
Skin and subcutaneous tissue disorders
Pruritus	14/137 (10.2%)		4/76 (5.3%)
Rash	8/137 (5.8%)		2/76 (2.6%)
Rash papular	11/137 (8%)		2/76 (2.6%)
Vascular disorders
Hot flush	7/137 (5.1%)		0/76 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Sponsor reserves the right to review results publications prior to public release and can delay such publications for a period greater than 60 days but no more than 120 days from the date that the publication is submitted to the Sponsor for review. Sponsor can require changes to the publication to protect Sponsor's intellectual property rights and/or confidential information and reserves the right to limit publication timing and scope of data published based on the number of study locations.