Back to resultsA 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
Primary Purpose
Multidrug Resistant Tuberculosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Delamanid
Delamanid Pediatric Formulation (DPF)
Optimized Background Regimen (OBR)
Sponsored by
About this trial
This is an interventional treatment trial for Multidrug Resistant Tuberculosis focused on measuring Tuberculosis, Tuberculosis, Multidrug-Resistant, Mycobacterium Infections, Actinomycetes Infections, Gram-Positive Infections, Bacterial Infections, Pediatric
Eligibility Criteria
Inclusion Criteria:
- Successfully completed Trial 242-12-232
- Confirmed diagnosis of MDR-TB OR
Presumptive diagnosis of pulmonary or extrapulmonary MDR-TB including one of the following:
- Clinical specimen suggestive of tuberculosis disease
- Persistent cough lasting > 2 weeks
- Fever, weight loss, and failure to thrive
- Findings on recent chest radiograph (prior to Visit 1) consistent with TB AND
- Household contact with a person with known MDR-TB or with a person who died while appropriately taking drugs for sensitive TB OR
- On first-line TB treatment but with no clinical improvement
- Negative urine pregnancy test for female participants who have reached menarche
- Written informed consent/assent
Exclusion Criteria:
- Participants who have not completed Trial 242-12-232
- Laboratory evidence of active hepatitis B or C
- Children with body weight < 5.5 kg
- For participants with human-immunodeficiency virus (HIV) co-infection, cluster difference-4 (CD4) cell count ≤ 1000/mm^3 for children 1-5 years old, and ≤ 1500/mm^3 for children less than 1 year old
- History of allergy to metronidazole and any disease or condition in which metronidazole is required
- Use of amiodarone within 12 months or use of other predefined antiarrhythmic medications within 30 days prior to first dose of delamanid
- Serious concomitant conditions
- Pre-existing cardiac conditions
- Abnormalities in Screening electrocardiogram (ECG) [including atrio-ventricular (AV) block, blood brain barrier (BBB) or hemi-block, QRS prolongation > 120 milliseconds (ms), or QT interval corrected by Fridericia's formula (QTcF) > 450 ms in both males and females]
- Concomitant condition such as renal impairment characterized by serum creatinine levels > 1.5 mg/dL, hepatic impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal (ULN)), or hyperbilirubinemia characterized by total bilirubin > 2x ULN
- Current diagnosis of severe malnutrition or kwashiorkor
- Positive urine drug screen (Groups 1 and 2 only)
- Rifampicin and/or moxifloxacin within 1 week prior to the first dose of delamanid and/or any prior or concurrent use of bedaquiline
- Lansky Play Performance Score < 50 (not applicable for children < 1 year old) or Karnofsky Score < 50
- Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than delamanid given as IMP in Trial 242-12-232
- Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form (Groups 1 and 2 only)
Sites / Locations
- De La Salle Health Sciences Institute
- Lung Center of the Philippines
- Brooklyn Chest Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
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
Arm 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)].
Outcomes
Primary Outcome Measures
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)
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).
Number of Participants With Abnormal Physical Examination Values
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.
Number of Participants With Clinically Significant Abnormal Vital Sign Values
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.
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
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.
Number of Participants With Clinically Significant Laboratory Test Abnormalities
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.
Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid
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.
POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid
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.
POPPK Model Point Estimate for Absorption Rate Constant (Ka) of Delamanid
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.
POPPK Model Point Estimate for Absorption Lag Time (ALAG1) of Delamanid
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.
Secondary Outcome Measures
Baseline QT Interval (QTcB) Effect
The 12-lead ECG was performed to obtain recordings of heart rate (QT interval) to analyze QTcB effect.
PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations
The linear mixed effects model was applied to characterize the concentration-QTcB relationship of delamanid/DM-6705 to obtain population slope estimate.
Number of Participants With Treatment Outcome as Assessed by Principal Investigator
Treatment outcome was defined as favorable (cured and completed treatment) and unfavorable (lost to follow-up or died).
Number of Participants With Abnormal Chest X-ray
The data for the chest X-ray with abnormality, as assessed by investigator is reported.
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis
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.
Sputum Culture Conversion (SCC)
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.
Number of Participants With Palatability Score as Assessed by the Investigator
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.
Number of Participants With Palatability Score as Assessed by the Parent or Participant
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.
Full Information
NCT ID
NCT01859923
First Posted
May 15, 2013
Last Updated
October 29, 2020
Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT01859923
Brief Title
A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
Official Title
Phase 2, Open-label, Multiple-dose Trial to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of Delamanid (OPC-67683) in Pediatric Multidrug-resistant Tuberculosis Patients on Therapy With an Optimized Background Regimen of Anti-tuberculosis Drugs Over a 6-Month Treatment Period
Study Type
Interventional
2. Study Status
Record Verification Date
October 2020
Overall Recruitment Status
Completed
Study Start Date
July 20, 2013 (Actual)
Primary Completion Date
January 13, 2020 (Actual)
Study Completion Date
January 13, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Pharmaceutical Development & Commercialization, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this trial is to assess the safety, tolerability, pharmacokinetics, and efficacy of long-term (6-month) treatment with delamanid plus an optimized background regimen (OBR) of other anti-tuberculosis drugs in pediatric participants who completed Study 242-12-232 (NCT01856634).
Detailed Description
This study will assess the safety, tolerability, pharmacokinetics, and efficacy of delamanid plus an optimized background regimen in pediatric participants with MDR-TB over a 6-month treatment period. This long-term study, an extension of Study 242-12-232, will be conducted in participants who have completed Study 242-12-232.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multidrug Resistant Tuberculosis
Keywords
Tuberculosis, Tuberculosis, Multidrug-Resistant, Mycobacterium Infections, Actinomycetes Infections, Gram-Positive Infections, Bacterial Infections, Pediatric
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
37 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: 12 to 17 Years of Age
Arm Type
Experimental
Arm 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.
Arm Title
Group 2: 6 to 11 Years of Age
Arm Type
Experimental
Arm Description
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.
Arm Title
Group 3: 3 to 5 Years of Age
Arm Type
Experimental
Arm 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.
Arm Title
Group 4: Birth to 2 Years of Age
Arm Type
Experimental
Arm Description
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)].
Intervention Type
Drug
Intervention Name(s)
Delamanid
Other Intervention Name(s)
OPC-67683
Intervention Description
Participants received adult formulation delamanid as per regimen specified in the arm description. Morning dose of the delamanid BID regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard dinner meal.
Intervention Type
Drug
Intervention Name(s)
Delamanid Pediatric Formulation (DPF)
Intervention Description
Participants received delamanid as an extemporaneous suspension using the delamanid pediatric dispersible tablet formulation. Morning dose of the delamanid BID/once daily (QD) regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard meal.
Intervention Type
Drug
Intervention Name(s)
Optimized Background Regimen (OBR)
Intervention Description
Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Primary Outcome Measure Information:
Title
Number of Participants With At Least One Treatment Emergent Adverse Event (TEAE)
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)
Title
Number of Participants With Abnormal Physical Examination Values
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)
Title
Number of Participants With Clinically Significant Abnormal Vital Sign Values
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)
Title
Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Values
Description
The criteria for clinically significant abnormal ECG values were ventricular rate outlier (<50 bpm and decrease of >=25%, >100 bpm and increase of >=25%), PR outlier (increase of >=25% when PR >200 milliseconds (ms)), QRS outlier (increase of >=25% when QRS >100 ms), QT (new onset (in treatment period but not at Baseline) [>500 ms]), QT interval corrected by Bazett's formula (QTcB) (new onset [>450, >480, >500 ms], increase of >=30 ms and <= 60 ms or increase of >60 ms), QT interval corrected by Fridericia's formula (QTcF) (new onset [>450, >480, >500 ms], increase of >=30 ms and <= 60 ms or increase of >60 ms), new abnormal U waves, new ST segment changes, new T wave changes, new abnormal rhythm, new conduction abnormality were reported as categories. Only categories with data are reported.
Time Frame
From the first dose of study drug up to the end of the Post-treatment Follow-up Period (Up to Day 365)
Title
Number of Participants With Clinically Significant Laboratory Test Abnormalities
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)
Title
Population Pharmacokinetic (POPPK) Model Point Estimate for Central Clearance (L) and Inter-compartmental Clearance (Q) of Delamanid
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
Title
POPPK Model Point Estimate for Central Volume of Distribution (Vc) and Peripheral Volume of Distribution (Vp) of Delamanid
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
Title
POPPK Model Point Estimate for Absorption Rate Constant (Ka) of Delamanid
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
Title
POPPK Model Point Estimate for Absorption Lag Time (ALAG1) of Delamanid
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
Secondary Outcome Measure Information:
Title
Baseline QT Interval (QTcB) Effect
Description
The 12-lead ECG was performed to obtain recordings of heart rate (QT interval) to analyze QTcB effect.
Time Frame
Baseline (Day -1)
Title
PK/PD Relationship: POPPK Model Point Estimate for Slope of Linear Mixed Effects Model for Change in QTcB Interval Versus Delamanid Plasma Concentrations
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
Title
Number of Participants With Treatment Outcome as Assessed by Principal Investigator
Description
Treatment outcome was defined as favorable (cured and completed treatment) and unfavorable (lost to follow-up or died).
Time Frame
Month 24
Title
Number of Participants With Abnormal Chest X-ray
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)
Title
Number of Participants With Investigator-Assessed Signs and Symptoms of Tuberculosis
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)
Title
Sputum Culture Conversion (SCC)
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)
Title
Number of Participants With Palatability Score as Assessed by the Investigator
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
Title
Number of Participants With Palatability Score as Assessed by the Parent or Participant
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
0 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Successfully completed Trial 242-12-232
Confirmed diagnosis of MDR-TB OR
Presumptive diagnosis of pulmonary or extrapulmonary MDR-TB including one of the following:
Clinical specimen suggestive of tuberculosis disease
Persistent cough lasting > 2 weeks
Fever, weight loss, and failure to thrive
Findings on recent chest radiograph (prior to Visit 1) consistent with TB AND
Household contact with a person with known MDR-TB or with a person who died while appropriately taking drugs for sensitive TB OR
On first-line TB treatment but with no clinical improvement
Negative urine pregnancy test for female participants who have reached menarche
Written informed consent/assent
Exclusion Criteria:
Participants who have not completed Trial 242-12-232
Laboratory evidence of active hepatitis B or C
Children with body weight < 5.5 kg
For participants with human-immunodeficiency virus (HIV) co-infection, cluster difference-4 (CD4) cell count ≤ 1000/mm^3 for children 1-5 years old, and ≤ 1500/mm^3 for children less than 1 year old
History of allergy to metronidazole and any disease or condition in which metronidazole is required
Use of amiodarone within 12 months or use of other predefined antiarrhythmic medications within 30 days prior to first dose of delamanid
Serious concomitant conditions
Pre-existing cardiac conditions
Abnormalities in Screening electrocardiogram (ECG) [including atrio-ventricular (AV) block, blood brain barrier (BBB) or hemi-block, QRS prolongation > 120 milliseconds (ms), or QT interval corrected by Fridericia's formula (QTcF) > 450 ms in both males and females]
Concomitant condition such as renal impairment characterized by serum creatinine levels > 1.5 mg/dL, hepatic impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal (ULN)), or hyperbilirubinemia characterized by total bilirubin > 2x ULN
Current diagnosis of severe malnutrition or kwashiorkor
Positive urine drug screen (Groups 1 and 2 only)
Rifampicin and/or moxifloxacin within 1 week prior to the first dose of delamanid and/or any prior or concurrent use of bedaquiline
Lansky Play Performance Score < 50 (not applicable for children < 1 year old) or Karnofsky Score < 50
Administered an investigational medicinal product (IMP) within 1 month prior to Visit 1 other than delamanid given as IMP in Trial 242-12-232
Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form (Groups 1 and 2 only)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Melchor VG Frias, IV, MD
Organizational Affiliation
De La Salle Health Sciences Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Anjanette Reyes-De Leon, MD
Organizational Affiliation
Lung Center of the Philippines
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Louvina van der Laan, MD
Organizational Affiliation
Brooklyn Chest Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
De La Salle Health Sciences Institute
City
Dasmariñas
State/Province
Cavite
Country
Philippines
Facility Name
Lung Center of the Philippines
City
Quezon City
State/Province
Metro Manila
Country
Philippines
Facility Name
Brooklyn Chest Hospital
City
Ysterplaat
State/Province
Cape Town
Country
South Africa
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymized Individual participant data (IPD) that underlie the results of this study will be shared with researchers to achieve aims pre-specified in a methodologically sound research proposal. Small studies with less than 25 participants are excluded from data sharing.
IPD Sharing Time Frame
Data will be available after marketing approval in global markets, or beginning 1-3 years following article publication. There is no end date to the availability of the data.
IPD Sharing Access Criteria
Otsuka will share data on an Otsuka-owned remotely accessible data sharing platform with Python and R analytical software. Research requests should be directed to clinicaltransparency@Otsuka-us.com
IPD Sharing URL
https://clinical-trials.otsuka.com
Citations:
PubMed Identifier
35404075
Citation
Garcia-Prats AJ, Frias M, van der Laan L, De Leon A, Gler MT, Schaaf HS, Hesseling AC, Malikaarjun S, Hafkin J. Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase I/II Clinical Trial. Antimicrob Agents Chemother. 2022 May 17;66(5):e0214421. doi: 10.1128/aac.02144-21. Epub 2022 Apr 11.
Results Reference
derived
Learn more about this trial
A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
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