Trial Outcomes & Findings for A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB) (NCT NCT01859923)

Last Updated: 2020-11-23

Results Overview

An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant and that does not necessarily have a causal relationship with the treatment. A TEAE is defined as an AE that occurred after the administration of investigational medicinal product (IMP).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

37 participants

Primary outcome timeframe

From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Results posted on

2020-11-23

Participant Flow

Participants took part in study at 3 investigative sites in Philippines and South Africa from July 20, 2013 to January 13, 2020. Participants received delamanid up to Day 182 in the treatment period and were followed up to Day 365 for safety and efficacy and up to Day 730 (Month 24) for treatment outcome.

Pediatric participants with a diagnosis of multidrug-resistant tuberculosis (MDR-TB) who were on therapy with an optimized background regimen (OBR) of anti-tuberculosis drugs and completed study 242-12-232 (NCT01856634) were enrolled in this extension study 242-12-233 to receive delamanid based on the participant's age and weight.

Participant milestones

Participant milestones
Measure	Group 1: 12 to 17 Years of Age Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) plus optimized background regimen (OBR) up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Overall Study STARTED	7	6	12	12
Overall Study COMPLETED	7	6	11	11
Overall Study NOT COMPLETED	0	0	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Group 1: 12 to 17 Years of Age Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 milligrams (mg) (2x50 mg tablets), orally, twice daily (BID) plus optimized background regimen (OBR) up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Overall Study Adverse Event	0	0	1	1

Baseline Characteristics

A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].	Total n=37 Participants Total of all reporting groups
Age, Continuous	15.37 years STANDARD_DEVIATION 1.63 • n=5 Participants	9.51 years STANDARD_DEVIATION 1.49 • n=7 Participants	4.37 years STANDARD_DEVIATION 0.98 • n=5 Participants	1.79 years STANDARD_DEVIATION 0.59 • n=4 Participants	6.45 years STANDARD_DEVIATION 5.18 • n=21 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	19 Participants n=21 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	18 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=5 Participants	6 Participants n=7 Participants	12 Participants n=5 Participants	12 Participants n=4 Participants	37 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Asian	7 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants	6 Participants n=4 Participants	10 Participants n=21 Participants
Region of Enrollment Philippines	7 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	6 Participants n=4 Participants	25 Participants n=21 Participants
Region of Enrollment South Africa	0 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	12 Participants n=21 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)	7 Participants	6 Participants	12 Participants	12 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation. Overall number of participants analyzed are the participants with data available for analyses.

Physical examination included the examination of the abdomen; extremities; head, eyes, ears, nose (HEENT); neurological; skin and mucosae; thorax; urogenital; audiometry assessment and visual assessment. Participants with abnormal values, as assessed by the investigator were reported.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=11 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Abnormal Physical Examination Values Abdomen	1 Participants	1 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Physical Examination Values Extremities	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Physical Examination Values HEENT	7 Participants	6 Participants	12 Participants	10 Participants
Number of Participants With Abnormal Physical Examination Values Neurological	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Physical Examination Values Skin and Mucosae	2 Participants	6 Participants	6 Participants	8 Participants
Number of Participants With Abnormal Physical Examination Values Thorax	5 Participants	2 Participants	6 Participants	7 Participants
Number of Participants With Abnormal Physical Examination Values Urogenital	0 Participants	0 Participants	1 Participants	3 Participants
Number of Participants With Abnormal Physical Examination Values Audiometry Assessment	4 Participants	3 Participants	9 Participants	7 Participants
Number of Participants With Abnormal Physical Examination Values Visual Assessment	0 Participants	1 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Vital signs included weight (kg), height (cm), body temperature (degree Celsius), heart rate (beats/min), respiratory rate (breaths/minute), systolic and diastolic blood pressure (mm Hg), body mass index (BMI) (kg/m\^2). The criteria for clinically significant abnormal value for weight was decrease or increase of \>=5% in body weight relative to Baseline. Only categories with data for potentially clinically significant abnormal vital sign parameter values are reported.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=11 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Clinically Significant Abnormal Vital Sign Values Decrease of >=5% in Body Weight	0 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Clinically Significant Abnormal Vital Sign Values Increase of >=5% in Body Weight	4 Participants	2 Participants	10 Participants	10 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

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.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=11 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values Ventricular Rate Outliers, Notable Increases	1 Participants	0 Participants	1 Participants	4 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QRS Outliers	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcB, New Onset (>480 ms)	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcB, New Onset (>450 ms)	7 Participants	2 Participants	8 Participants	5 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcB, New Onset (Change >= 30 and <=60 ms)	5 Participants	3 Participants	8 Participants	9 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcB, New Onset (Change > 60 ms)	1 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcF, New Onset (>450 ms)	3 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcF, New Onset (Change >= 30 and <=60 ms)	5 Participants	2 Participants	6 Participants	9 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values QTcF, New Onset (Change > 60 ms)	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values New Abnormal Rhythm	5 Participants	4 Participants	6 Participants	1 Participants
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values New Conduction Abnormality	6 Participants	5 Participants	5 Participants	8 Participants

PRIMARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

Laboratory assessments included parameters for serum chemistry, hematology and urinalysis along with adrenocorticotropic hormone, serum cortisol, free thyroxine, thyroid-stimulating hormone (TSH), and high sensitivity C-reactive protein cell count. 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. The normal ranges for those laboratory parameters were potassium 3.4 - 5.4 milliequivalents/liter (mEq/L), uric acid 3.9 - 8.2 mg/dL, partial thromboplastin time (PTT) 9.7 - 12.3 sec, platelet count 180 - 440 thousands platelets/μL.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Clinically Significant Laboratory Test Abnormalities Elevated Uric Acid	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Elevated Potassium	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Elevated PTT	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Clinically Significant Laboratory Test Abnormalities Low Platelet Count	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238

Population: Population Pharmacokinetic (PK)/Pharmacodynamic (PD) analysis sample included all the participants with data available for PK/PD analysis.

Central clearance is defined as plasma volume in the vascular compartment that is cleared of drug per unit of time. Inter-compartmental clearance is defined as a ratio of the drug's distribution rate between the central compartment and the peripheral compartments over its circulating concentration (L/hr). Population point estimates were based on POPPK analysis to find one measure each for both L and Q. The exposure data were pooled across visits and participants to identify POPPK parameter estimates and were reported for delamanid.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid Central Clearance (L)	18.1 L/hr	—	—	—
Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid Inter-compartmental Clearance (Q)	105 L/hr	—	—	—

PRIMARY outcome

Timeframe: Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238

Population: Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.

Vc is defined as the theoretical volume that would be necessary to contain the total amount of an administered drug at the same concentration that it is observed in the blood plasma. Vp is defined as the apparent volume needed to account for the total amount of drug in the body if the drug was evenly distributed throughout the body and in the same concentration as the site of sample collection such as peripheral venous plasma. Population point estimates were based on POPPK analysis to find one measure each for both Vc and Vp. The exposure data were pooled across visits and participants to identify POPPK parameter estimates and were reported for delamanid.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid Central Volume of Distribution (Vc)	254 liters (L)	—	—	—
POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid Peripheral Volume of Distribution (Vp)	347 liters (L)	—	—	—

PRIMARY outcome

Timeframe: Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238

Population: Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.

Ka is defined as a measure of rate at which a drug enters into the circulatory system. Population point estimate for Ka was based on population PK analysis to find one measure. Population point estimates were based on POPPK analysis to find one measure for Ka. The exposure data were pooled across visits and participants to identify POPPK parameter estimates and were reported for delamanid.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
POPPK Model Point Estimate for Absorption Rate Constant (Ka) of Delamanid	0.254 per hour (1/hr)	—	—	—

PRIMARY outcome

Timeframe: Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238

Population: Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.

ALAG1 is defined as the time delay prior to the commencement of drug absorption. Population point estimates were based on POPPK analysis to find one measure for ALAG1. The exposure data were pooled across visits and participants to identify POPPK parameter estimates and were reported for delamanid.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
POPPK Model Point Estimate for Absorption Lag Time (ALAG1) of Delamanid	1.38 hour (hr)	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day -1)

Population: Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.

The 12-lead ECG was performed to obtain recordings of heart rate (QT interval) to analyze QTcB effect.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Baseline QT Interval (QTcB) Effect Delamanid	0.0318 ms Interval -0.113 to 0.177	—	—	—
Baseline QT Interval (QTcB) Effect Metabolite DM-6705	0.0309 ms Interval -0.112 to 0.174	—	—	—

SECONDARY outcome

Timeframe: Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238

Population: Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.

The linear mixed effects model was applied to characterize the concentration-QTcB relationship of delamanid/DM-6705 to obtain population slope estimate.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=37 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations Delamanid	0.00792 ms/[ng/mL] Interval -0.00132 to 0.0172	—	—	—
PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations Metabolite DM-6705	0.0613 ms/[ng/mL] Interval 0.016 to 0.107	—	—	—

SECONDARY outcome

Timeframe: Month 24

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

Treatment outcome was defined as favorable (cured and completed treatment) and unfavorable (lost to follow-up or died).

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Treatment Outcome as Assessed by Principal Investigator Favorable (Cured + Treatment Completed)	6 Participants	6 Participants	10 Participants	11 Participants
Number of Participants With Treatment Outcome as Assessed by Principal Investigator Unfavorable (Lost To Follow-up + Died)	1 Participants	0 Participants	2 Participants	1 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

The data for the chest X-ray with abnormality, as assessed by investigator is reported.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Abnormal Chest X-ray	7 Participants	6 Participants	12 Participants	11 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

The following signs and symptoms of tuberculosis were assessed by the investigator: cough, fever, weight loss, failure to thrive, hemoptysis, dyspnea, chest pain, night sweats and loss of appetite.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=7 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 Participants Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 Participants Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Cough	6 Participants	4 Participants	3 Participants	7 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Fever	1 Participants	2 Participants	2 Participants	5 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Weight Loss	3 Participants	5 Participants	7 Participants	9 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Failure to Thrive	0 Participants	1 Participants	0 Participants	3 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Hemoptysis	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Dyspnea	1 Participants	1 Participants	3 Participants	2 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Chest Pain	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Night Sweats	0 Participants	0 Participants	1 Participants	2 Participants
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis Loss of Appetite	1 Participants	2 Participants	2 Participants	6 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)

Population: Data for SCC could not be collected due to the paucity of sputum production in the participants.

SCC was defined as a sputum specimen from a participant negative for growth of Mycobacterium tuberculosis (MTB), followed by at least one confirmatory negative sputum culture at least 27 days after the first negative sputum test and not followed by any sputum cultures positive for growth.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Days 1, 28, 56 and 182

Population: Participants from the safety sample aged below 5 years (Groups 3 and 4) and who received any amount of IMP in this study, regardless of any protocol deviation or violation were analyzed for this outcome measure. Number analyzed is the number of participants with data available for analyses at the given time point.

The palatability of the pediatric formulation was assessed using an age-appropriate visual hedonic scale and clinical assessment (Groups 3 and 4 only). The palatability result was based on 1 of 5 responses: 1=Dislike very much, 2=Dislike a little, 3=Neither liked nor disliked, 4=Like a little, 5=Like very much. Participants were categorized based on different scores. The data per the investigator score are reported.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=12 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=12 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Palatability Score as Assessed by the Investigator Day 1 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 1 · Dislike a Little	0 Participants	2 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 1 · Neither Liked Nor Disliked	1 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 1 · Like a Little	2 Participants	2 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 1 · Like Very Much	9 Participants	8 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 28 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 28 · Dislike a Little	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 28 · Neither Liked Nor Disliked	2 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 28 · Like a Little	1 Participants	2 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 28 · Like Very Much	9 Participants	9 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 56 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 56 · Dislike a Little	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 56 · Neither Liked Nor Disliked	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 56 · Like a Little	2 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 56 · Like Very Much	10 Participants	11 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 182 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 182 · Dislike a Little	0 Participants	1 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 182 · Neither Liked Nor Disliked	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 182 · Like a Little	1 Participants	5 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Investigator Day 182 · Like Very Much	11 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: Days 1, 28, 56 and 182

The palatability of the pediatric formulation was assessed using an age-appropriate visual hedonic scale and clinical assessment (Groups 3 and 4 only). The palatability result was based on 1 of 5 responses: 1=Dislike very much, 2=Dislike a little, 3=Neither liked nor disliked, 4=Like a little, 5=Like very much. The data per parent/patient score are reported. Participants were categorized based on different scores.

Outcome measures

Outcome measures
Measure	Group 1: 12 to 17 Years of Age n=12 Participants Participants 12 to 17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=12 Participants Participants 6 to 11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 1 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 1 · Dislike a Little	0 Participants	1 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 1 · Neither Liked Nor Disliked	1 Participants	1 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 1 · Like a Little	2 Participants	3 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 1 · Like Very Much	9 Participants	7 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 28 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 28 · Dislike a Little	1 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 28 · Neither Liked Nor Disliked	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 28 · Like a Little	1 Participants	3 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 28 · Like Very Much	10 Participants	8 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 56 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 56 · Dislike a Little	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 56 · Neither Liked Nor Disliked	1 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 56 · Like a Little	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 56 · Like Very Much	11 Participants	11 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 182 · Dislike Very Much	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 182 · Dislike a Little	0 Participants	0 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 182 · Neither Liked Nor Disliked	0 Participants	1 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 182 · Like a Little	1 Participants	4 Participants	—	—
Number of Participants With Palatability Score as Assessed by the Parent or Participant Day 182 · Like Very Much	11 Participants	6 Participants	—	—

Adverse Events

Group 1: 12 to 17 Years of Age

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Group 2: 6 to 11 Years of Age

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Group 3: 3 to 5 Years of Age

Serious events: 2 serious events

Other events: 12 other events

Deaths: 1 deaths

Group 4: Birth to 2 Years of Age

Serious events: 5 serious events

Other events: 11 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Group 1: 12 to 17 Years of Age n=7 participants at risk Participants 12-17 years old (inclusive) received adult formulation of delamanid 100 mg (2x50 mg tablets), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 2: 6 to 11 Years of Age n=6 participants at risk Participants 6-11 years old (inclusive) received adult formulation delamanid 50 mg (1x50 mg tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 3: 3 to 5 Years of Age n=12 participants at risk Participants 3 to 5 years old (inclusive) received 25 mg pediatric formulation of delamanid (DPF - suspension prepared using dispersible tablet), orally, BID plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.	Group 4: Birth to 2 Years of Age n=12 participants at risk Participants from birth to 2 years old (inclusive) received DPF (suspension prepared using dispersible tablet) for 182 days plus OBR. Participants continued to receive OBR up to Day 365. The DPF dose was based on the participant's body weight during the baseline visit: * Participants \>10 kilograms (kg) received DPF 10 mg BID plus OBR * Participants \>8 kg and ≤10 kg received DPF 5 mg BID plus OBR * Participants ≥5.5 kg and ≤8 kg received DPF 5 mg once per day (QD) plus OBR Delamanid dose was adjusted as needed for Group 4 participants based on the weight measurement at specified study visits \[Visits 5 (Day 28), 7 (Day 56), 9 (Day 84), 11 (Day 126) and 12 (Day 154)\].
Blood and lymphatic system disorders Immune thrombocytopenic purpura	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Infections and infestations Lower respiratory tract infection	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Infections and infestations Oral candidiasis	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Infections and infestations Pneumonia	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	16.7% 2/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Infections and infestations Vulvovaginal candidiasis	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-Hodgkin's lymphoma	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	16.7% 1/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Nervous system disorders Lethargy	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Respiratory, thoracic and mediastinal disorders Bronchial hyperreactivity	0.00% 0/7 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/6 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	0.00% 0/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.	8.3% 1/12 • From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365) The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.

Other adverse events

Additional Information

Global Clinical Development

Otsuka Pharmaceutical Development & Commercialization, Inc.

Phone: 1-609-524-6788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER