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

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ClinicalTrials.gov Identifier: NCT01859923
Recruitment Status : Completed
First Posted : May 22, 2013
Results First Posted : November 23, 2020
Last Update Posted : November 23, 2020
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multidrug Resistant Tuberculosis
Interventions Drug: Delamanid
Drug: Delamanid Pediatric Formulation (DPF)
Drug: Optimized Background Regimen (OBR)
Enrollment 37
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description 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. 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. 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.

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)].

Period Title: Overall Study
Started 7 6 12 12
Completed 7 6 11 11
Not Completed 0 0 1 1
Reason Not Completed
Adverse Event             0             0             1             1
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age Total
Hide Arm/Group Description 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. 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. 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.

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 of all reporting groups
Overall Number of Baseline Participants 7 6 12 12 37
Hide Baseline Analysis Population Description
The Safety Sample included participants who received any amount of investigational medicinal product (IMP) in this study, regardless of any protocol deviation or violation.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 7 participants 6 participants 12 participants 12 participants 37 participants
15.37  (1.63) 9.51  (1.49) 4.37  (0.98) 1.79  (0.59) 6.45  (5.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 12 participants 12 participants 37 participants
Female
3
  42.9%
4
  66.7%
6
  50.0%
6
  50.0%
19
  51.4%
Male
4
  57.1%
2
  33.3%
6
  50.0%
6
  50.0%
18
  48.6%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 12 participants 12 participants 37 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
7
 100.0%
6
 100.0%
12
 100.0%
12
 100.0%
37
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 12 participants 12 participants 37 participants
Black or African American
0
   0.0%
0
   0.0%
2
  16.7%
0
   0.0%
2
   5.4%
Asian
7
 100.0%
4
  66.7%
8
  66.7%
6
  50.0%
25
  67.6%
Other
0
   0.0%
2
  33.3%
2
  16.7%
6
  50.0%
10
  27.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 12 participants 12 participants 37 participants
Philippines
7
 100.0%
4
  66.7%
8
  66.7%
6
  50.0%
25
  67.6%
South Africa
0
   0.0%
2
  33.3%
4
  33.3%
6
  50.0%
12
  32.4%
1.Primary Outcome
Title Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)
Hide Description 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).
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
7
 100.0%
6
 100.0%
12
 100.0%
12
 100.0%
2.Primary Outcome
Title Number of Participants With Abnormal Physical Examination Values
Hide Description 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.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
Abdomen
1
  14.3%
1
  16.7%
4
  33.3%
2
  18.2%
Extremities
2
  28.6%
0
   0.0%
1
   8.3%
1
   9.1%
HEENT
7
 100.0%
6
 100.0%
12
 100.0%
10
  90.9%
Neurological
1
  14.3%
0
   0.0%
1
   8.3%
1
   9.1%
Skin and Mucosae
2
  28.6%
6
 100.0%
6
  50.0%
8
  72.7%
Thorax
5
  71.4%
2
  33.3%
6
  50.0%
7
  63.6%
Urogenital
0
   0.0%
0
   0.0%
1
   8.3%
3
  27.3%
Audiometry Assessment
4
  57.1%
3
  50.0%
9
  75.0%
7
  63.6%
Visual Assessment
0
   0.0%
1
  16.7%
0
   0.0%
1
   9.1%
3.Primary Outcome
Title Number of Participants With Clinically Significant Abnormal Vital Sign Values
Hide Description 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.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
Decrease of >=5% in Body Weight
0
   0.0%
2
  33.3%
0
   0.0%
1
   9.1%
Increase of >=5% in Body Weight
4
  57.1%
2
  33.3%
10
  83.3%
10
  90.9%
4.Primary Outcome
Title Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
Hide 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 the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 11
Measure Type: Count of Participants
Unit of Measure: Participants
Ventricular Rate Outliers, Notable Increases
1
  14.3%
0
   0.0%
1
   8.3%
4
  36.4%
QRS Outliers
1
  14.3%
0
   0.0%
0
   0.0%
0
   0.0%
QTcB, New Onset (>480 ms)
1
  14.3%
1
  16.7%
1
   8.3%
0
   0.0%
QTcB, New Onset (>450 ms)
7
 100.0%
2
  33.3%
8
  66.7%
5
  45.5%
QTcB, New Onset (Change >= 30 and <=60 ms)
5
  71.4%
3
  50.0%
8
  66.7%
9
  81.8%
QTcB, New Onset (Change > 60 ms)
1
  14.3%
0
   0.0%
0
   0.0%
2
  18.2%
QTcF, New Onset (>450 ms)
3
  42.9%
2
  33.3%
0
   0.0%
0
   0.0%
QTcF, New Onset (Change >= 30 and <=60 ms)
5
  71.4%
2
  33.3%
6
  50.0%
9
  81.8%
QTcF, New Onset (Change > 60 ms)
1
  14.3%
0
   0.0%
0
   0.0%
1
   9.1%
New Abnormal Rhythm
5
  71.4%
4
  66.7%
6
  50.0%
1
   9.1%
New Conduction Abnormality
6
  85.7%
5
  83.3%
5
  41.7%
8
  72.7%
5.Primary Outcome
Title Number of Participants With Clinically Significant Laboratory Test Abnormalities
Hide Description 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.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Elevated Potassium
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
Elevated Uric Acid
1
  14.3%
0
   0.0%
1
   8.3%
0
   0.0%
Elevated PTT
0
   0.0%
1
  16.7%
2
  16.7%
0
   0.0%
Low Platelet Count
0
   0.0%
0
   0.0%
0
   0.0%
1
   8.3%
6.Primary Outcome
Title Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid
Hide Description 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.
Time Frame Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238
Hide Outcome Measure Data
Hide Analysis Population Description
Population Pharmacokinetic (PK)/Pharmacodynamic (PD) analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: L/hr
Central Clearance (L) 18.1
Inter-compartmental Clearance (Q) 105
7.Primary Outcome
Title POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid
Hide Description 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.
Time Frame Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238
Hide Outcome Measure Data
Hide Analysis Population Description
Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: liters (L)
Central Volume of Distribution (Vc) 254
Peripheral Volume of Distribution (Vp) 347
8.Primary Outcome
Title POPPK Model Point Estimate for Absorption Rate Constant (Ka) of Delamanid
Hide Description 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.
Time Frame Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238
Hide Outcome Measure Data
Hide Analysis Population Description
Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: per hour (1/hr)
0.254
9.Primary Outcome
Title POPPK Model Point Estimate for Absorption Lag Time (ALAG1) of Delamanid
Hide Description 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.
Time Frame Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238
Hide Outcome Measure Data
Hide Analysis Population Description
Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Measure Type: Number
Unit of Measure: hour (hr)
1.38
10.Secondary Outcome
Title Baseline QT Interval (QTcB) Effect
Hide Description The 12-lead ECG was performed to obtain recordings of heart rate (QT interval) to analyze QTcB effect.
Time Frame Baseline (Day -1)
Hide Outcome Measure Data
Hide Analysis Population Description
Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: ms
Delamanid
0.0318
(-0.113 to 0.177)
Metabolite DM-6705
0.0309
(-0.112 to 0.174)
11.Secondary Outcome
Title PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations
Hide Description The linear mixed effects model was applied to characterize the concentration-QTcB relationship of delamanid/DM-6705 to obtain population slope estimate.
Time Frame Predose on Days 1, 56, 154, and 182, 210 and at any time point on Days 14, 98, 189, 196, 203, and 238
Hide Outcome Measure Data
Hide Analysis Population Description
Population PK/PD analysis sample included all the participants with data available for PK/PD analysis.
Arm/Group Title Delamanid
Hide Arm/Group Description:
Participants received delamanid 25, 50 or 100 mg based on age and weight plus OBR up to Day 182. Participants continued to receive OBR up to Day 365.
Overall Number of Participants Analyzed 37
Mean (90% Confidence Interval)
Unit of Measure: ms/[ng/mL]
Delamanid
0.00792
(-0.00132 to 0.0172)
Metabolite DM-6705
0.0613
(0.016 to 0.107)
12.Secondary Outcome
Title Number of Participants With Treatment Outcome as Assessed by Principal Investigator
Hide Description Treatment outcome was defined as favorable (cured and completed treatment) and unfavorable (lost to follow-up or died).
Time Frame Month 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Favorable (Cured + Treatment Completed)
6
  85.7%
6
 100.0%
10
  83.3%
11
  91.7%
Unfavorable (Lost To Follow-up + Died)
1
  14.3%
0
   0.0%
2
  16.7%
1
   8.3%
13.Secondary Outcome
Title Number of Participants With Abnormal Chest X-ray
Hide Description The data for the chest X-ray with abnormality, as assessed by investigator is reported.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
7
 100.0%
6
 100.0%
12
 100.0%
11
  91.7%
14.Secondary Outcome
Title Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis
Hide Description 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.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 7 6 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Cough
6
  85.7%
4
  66.7%
3
  25.0%
7
  58.3%
Fever
1
  14.3%
2
  33.3%
2
  16.7%
5
  41.7%
Weight Loss
3
  42.9%
5
  83.3%
7
  58.3%
9
  75.0%
Failure to Thrive
0
   0.0%
1
  16.7%
0
   0.0%
3
  25.0%
Hemoptysis
2
  28.6%
0
   0.0%
0
   0.0%
0
   0.0%
Dyspnea
1
  14.3%
1
  16.7%
3
  25.0%
2
  16.7%
Chest Pain
1
  14.3%
1
  16.7%
0
   0.0%
0
   0.0%
Night Sweats
0
   0.0%
0
   0.0%
1
   8.3%
2
  16.7%
Loss of Appetite
1
  14.3%
2
  33.3%
2
  16.7%
6
  50.0%
15.Secondary Outcome
Title Sputum Culture Conversion (SCC)
Hide Description 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.
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Hide Outcome Measure Data
Hide Analysis Population Description
Data for SCC could not be collected due to the paucity of sputum production in the participants.
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.
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.
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.

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 Number of Participants Analyzed 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
16.Secondary Outcome
Title Number of Participants With Palatability Score as Assessed by the Investigator
Hide Description 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.
Time Frame Days 1, 28, 56 and 182
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.

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 Number of Participants Analyzed 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1 Number Analyzed 12 participants 12 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
2
  16.7%
Neither Liked Nor Disliked
1
   8.3%
0
   0.0%
Like a Little
2
  16.7%
2
  16.7%
Like Very Much
9
  75.0%
8
  66.7%
Day 28 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
0
   0.0%
Neither Liked Nor Disliked
2
  16.7%
0
   0.0%
Like a Little
1
   8.3%
2
  18.2%
Like Very Much
9
  75.0%
9
  81.8%
Day 56 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
0
   0.0%
Neither Liked Nor Disliked
0
   0.0%
0
   0.0%
Like a Little
2
  16.7%
0
   0.0%
Like Very Much
10
  83.3%
11
 100.0%
Day 182 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
1
   9.1%
Neither Liked Nor Disliked
0
   0.0%
0
   0.0%
Like a Little
1
   8.3%
5
  45.5%
Like Very Much
11
  91.7%
5
  45.5%
17.Secondary Outcome
Title Number of Participants With Palatability Score as Assessed by the Parent or Participant
Hide Description 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.
Time Frame Days 1, 28, 56 and 182
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description:
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.

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 Number of Participants Analyzed 12 12
Measure Type: Count of Participants
Unit of Measure: Participants
Day 1 Number Analyzed 12 participants 12 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
1
   8.3%
Neither Liked Nor Disliked
1
   8.3%
1
   8.3%
Like a Little
2
  16.7%
3
  25.0%
Like Very Much
9
  75.0%
7
  58.3%
Day 28 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
1
   8.3%
0
   0.0%
Neither Liked Nor Disliked
0
   0.0%
0
   0.0%
Like a Little
1
   8.3%
3
  27.3%
Like Very Much
10
  83.3%
8
  72.7%
Day 56 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
0
   0.0%
Neither Liked Nor Disliked
1
   8.3%
0
   0.0%
Like a Little
0
   0.0%
0
   0.0%
Like Very Much
11
  91.7%
11
 100.0%
Day 182 Number Analyzed 12 participants 11 participants
Dislike Very Much
0
   0.0%
0
   0.0%
Dislike a Little
0
   0.0%
0
   0.0%
Neither Liked Nor Disliked
0
   0.0%
1
   9.1%
Like a Little
1
   8.3%
4
  36.4%
Like Very Much
11
  91.7%
6
  54.5%
Time Frame From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Adverse Event Reporting Description The Safety Sample included participants who received any amount of IMP in this study, regardless of any protocol deviation or violation.
 
Arm/Group Title Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Hide Arm/Group Description 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. 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. 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.

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)].

All-Cause Mortality
Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   0/6 (0.00%)   1/12 (8.33%)   1/12 (8.33%) 
Hide Serious Adverse Events
Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)   1/6 (16.67%)   2/12 (16.67%)   5/12 (41.67%) 
Blood and lymphatic system disorders         
Immune thrombocytopenic purpura  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Infections and infestations         
Lower respiratory tract infection  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Oral candidiasis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Pneumonia  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  2/12 (16.67%) 
Vulvovaginal candidiasis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Non-Hodgkin's lymphoma  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Nervous system disorders         
Lethargy  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Respiratory, thoracic and mediastinal disorders         
Bronchial hyperreactivity  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group 1: 12 to 17 Years of Age Group 2: 6 to 11 Years of Age Group 3: 3 to 5 Years of Age Group 4: Birth to 2 Years of Age
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   7/7 (100.00%)   6/6 (100.00%)   12/12 (100.00%)   11/12 (91.67%) 
Blood and lymphatic system disorders         
Anaemia  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  1/12 (8.33%) 
Eosinophilia  1  2/7 (28.57%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Immune thrombocytopenic purpura  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Cardiac disorders         
Wolff-Parkinson-White syndrome  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Ear and labyrinth disorders         
Cerumen impaction  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Conductive deafness  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Middle ear effusion  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Deafness neurosensory  1  2/7 (28.57%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Endocrine disorders         
Hypothyroidism  1  0/7 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  2/12 (16.67%) 
Eye disorders         
Conjunctivitis allergic  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Vernal keratoconjunctivitis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Gastrointestinal disorders         
Abdominal pain  1  1/7 (14.29%)  1/6 (16.67%)  1/12 (8.33%)  0/12 (0.00%) 
Abdominal pain lower  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Abdominal pain upper  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Aphthous ulcer  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Constipation  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Dental caries  1  2/7 (28.57%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Dyspepsia  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Gingival swelling  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Lip dry  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Lip ulceration  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Mouth ulceration  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Oral discomfort  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Toothache  1  0/7 (0.00%)  2/6 (33.33%)  1/12 (8.33%)  0/12 (0.00%) 
Vomiting  1  2/7 (28.57%)  1/6 (16.67%)  2/12 (16.67%)  1/12 (8.33%) 
General disorders         
Infusion site extravasation  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Pain  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Pyrexia  1  2/7 (28.57%)  0/6 (0.00%)  2/12 (16.67%)  1/12 (8.33%) 
Infections and infestations         
Acarodermatitis  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  3/12 (25.00%) 
Ascariasis  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Bronchitis  1  1/7 (14.29%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Folliculitis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Gastroenteritis  1  1/7 (14.29%)  1/6 (16.67%)  1/12 (8.33%)  4/12 (33.33%) 
Genital candidiasis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Gingivitis  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Helminthic infection  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Impetigo  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Lower respiratory tract infection  1  0/7 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  2/12 (16.67%) 
Mumps  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Nasopharyngitis  1  3/7 (42.86%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Oral candidiasis  1  1/7 (14.29%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Otitis media  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  3/12 (25.00%) 
Otitis media acute  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Parasitic gastroenteritis  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/12 (16.67%) 
Pharyngotonsillitis  1  1/7 (14.29%)  1/6 (16.67%)  1/12 (8.33%)  0/12 (0.00%) 
Pneumonia  1  1/7 (14.29%)  1/6 (16.67%)  3/12 (25.00%)  2/12 (16.67%) 
Pustule  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Pyelonephritis acute  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Pyuria  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Respiratory tract infection  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  4/12 (33.33%) 
Respiratory tract infection viral  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Rhinitis  1  1/7 (14.29%)  2/6 (33.33%)  0/12 (0.00%)  0/12 (0.00%) 
Rubella  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Subcutaneous abscess  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Systemic viral infection  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Tinea infection  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Tinea versicolour  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Tooth abscess  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Upper respiratory tract infection  1  4/7 (57.14%)  3/6 (50.00%)  5/12 (41.67%)  2/12 (16.67%) 
Urinary tract infection  1  3/7 (42.86%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Viral infection  1  1/7 (14.29%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Viral upper respiratory tract infection  1  1/7 (14.29%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Injury, poisoning and procedural complications         
Animal bite  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Concussion  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Contusion  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Craniocerebral injury  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  2/12 (16.67%) 
Eye injury  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Muscle strain  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Skin abrasion  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Skin laceration  1  0/7 (0.00%)  1/6 (16.67%)  2/12 (16.67%)  1/12 (8.33%) 
Tooth injury  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Investigations         
Activated partial thromboplastin time prolonged  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Alanine aminotransferase increased  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Blood corticotrophin increased  1  0/7 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/12 (8.33%) 
Coagulation time prolonged  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Hepatic enzyme increased  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Liver function test increased  1  0/7 (0.00%)  0/6 (0.00%)  2/12 (16.67%)  1/12 (8.33%) 
Prothrombin time prolonged  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  2/12 (16.67%) 
Weight decreased  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  3/12 (25.00%) 
Metabolism and nutrition disorders         
Decreased appetite  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Hyperuricaemia  1  2/7 (28.57%)  1/6 (16.67%)  4/12 (33.33%)  3/12 (25.00%) 
Hypokalaemia  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Musculoskeletal and connective tissue disorders         
Arthralgia  1  3/7 (42.86%)  2/6 (33.33%)  3/12 (25.00%)  0/12 (0.00%) 
Arthritis  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Bone pain  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Bursitis  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Costochondritis  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Muscular weakness  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Musculoskeletal chest pain  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Myalgia  1  2/7 (28.57%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Pain In extremity  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Soft tissue swelling  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Nervous system disorders         
Amnesia  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Dizziness  1  2/7 (28.57%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Headache  1  5/7 (71.43%)  3/6 (50.00%)  2/12 (16.67%)  0/12 (0.00%) 
Paraesthesia  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Psychomotor hyperactivity  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Psychiatric disorders         
Abnormal behaviour  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Aggression  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Depression  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Hallucination  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Insomnia  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Renal and urinary disorders         
Dysuria  1  2/7 (28.57%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Reproductive system and breast disorders         
Menorrhagia  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Asthma  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Cough  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Oropharyngeal pain  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Skin and subcutaneous tissue disorders         
Angioedema  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Butterfly rash  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  1/12 (8.33%) 
Dermatitis  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Dermatitis diaper  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Eczema  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Rash maculo-papular  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Rash papular  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Skin discolouration  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Skin fissures  1  1/7 (14.29%)  0/6 (0.00%)  0/12 (0.00%)  0/12 (0.00%) 
Skin hyperpigmentation  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Skin lesion  1  0/7 (0.00%)  1/6 (16.67%)  0/12 (0.00%)  0/12 (0.00%) 
Urticaria  1  0/7 (0.00%)  0/6 (0.00%)  0/12 (0.00%)  1/12 (8.33%) 
Urticaria papular  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Social circumstances         
Sexual abuse  1  0/7 (0.00%)  0/6 (0.00%)  1/12 (8.33%)  0/12 (0.00%) 
Vascular disorders         
Haematoma  1  0/7 (0.00%)  1/6 (16.67%)  1/12 (8.33%)  0/12 (0.00%) 
1
Term from vocabulary, MedDRA (22.1)
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Global Clinical Development
Organization: Otsuka Pharmaceutical Development & Commercialization, Inc.
Phone: 1-609-524-6788
EMail: clinicaltransparency@otsuka-us.com
Layout table for additonal information
Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01859923    
Other Study ID Numbers: 242-12-233
2012-004620-38 ( EudraCT Number )
First Submitted: May 15, 2013
First Posted: May 22, 2013
Results First Submitted: October 29, 2020
Results First Posted: November 23, 2020
Last Update Posted: November 23, 2020