- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01856634
Pharmacokinetic and Safety Trial to Determine the Appropriate Dose for Pediatric Patients With Multidrug Resistant Tuberculosis
Phase 1, Open-label, Multiple-dose, and Age De-escalation Trial to Assess the Pharmacokinetics, Safety and Tolerability of Delamanid (OPC 67683) in Pediatric Multidrug-resistant Tuberculosis Patients on Therapy With an Optimized Background Regimen of Anti-tuberculosis Drugs
Study Overview
Status
Conditions
Detailed Description
This trial will investigate the pharmacokinetics (PK) and safety of delamanid administered for 10 days to pediatric patients aged birth to 17 years who are also on therapy with an optimized background regimen. The purpose of the trial is to determine which dose in pediatric MDR-TB patients will result in delamanid plasma exposure similar to efficacious plasma exposure in adult MDR-TB patients. This is an age de-escalation trial in four groups:
Group 1: 12 to 17 years (100 mg BID; n=6) Group 2: 6 to 11 years (50 mg BID; n=6) Group 3: 3 to 5 years (25 mg BID; n=12) Group 4: Birth to 2 years (Dose based on patient's body weight, n=12)
- Patients > 10 kg will receive 10 mg BID
- Patients > 8 kg and ≤ 10 kg will receive 5 mg BID
- Patient ≤ to 8 kg will receive 5 mg QD
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Cavite
-
Dasmariñas, Cavite, Philippines, 4114
- De La Salle Health Sciences Institute
-
-
-
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Cape Town
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Ysterplaat, Cape Town, South Africa
- Brooklyn Chest Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Confirmed diagnosis of MDR-TB OR
Presumptive diagnosis of MDR-TB including one of the following:
- Clinical specimen suggestive of TB
- 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 of a person with known MDR-TB or 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 patients who have reached menarche
- Written informed consent/assent
Exclusion Criteria:
- Laboratory evidence of active hepatitis B or C
- Children with body weight < 5.5 kg
- For patients with HIV co-infection, CD4 cell count ≤ 1000/mm3 for children 1-5 years old, and ≤ 1500/mm3 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
- Preexisting cardiac conditions
- Abnormalities in Screening ECG (including AV block, BBB or hemi-block, QRS prolongation > 120 msec, or QTcF > 450 msec in both males and females)
- Concomitant condition such as renal impairment characterized by serum creatinine levels >1.5 mg/dL, hepatic impairment (ALT or AST > 3x 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 IMP within 1 month prior to Visit 1
- Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the information consent form (Groups 1 and 2 only)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Group 1: 12 to 17 years of age
Group 1: 100 mg Delamanid BID for 10 days + OBR
|
100 mg Delamanid BID for 10 days
Other Names:
Selection and administration of the treatment medications (i.e.
OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Other Names:
|
Experimental: Group 2: 6 to 11 years of age
50 mg Delamanid BID for 10 days + OBR
|
Selection and administration of the treatment medications (i.e.
OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Other Names:
50 mg Delamanid BID for 10 days
Other Names:
|
Experimental: Group 3: 3 to 5 years of age
25 mg Pediatric Formulation Delamanid BID for 10 days + OBR
|
Selection and administration of the treatment medications (i.e.
OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Other Names:
25 mg Pediatric Formulation Delamanid BID for 10 days
Other Names:
|
Experimental: Group 4: Birth to 2 years of age
Delamanid Pediatric Formulation (DPF) for 10 days + OBR. DPF dose based on patient's body weight during baseline visit:
|
Selection and administration of the treatment medications (i.e.
OBRs) will be based on WHO's Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines in each country
Other Names:
Patients > 10 kg will receive DPF 10 mg BID for 10 days
Other Names:
Patients > 8 kg and ≤ 10 kg will receive DPF 5 mg BID for 10 days Patients ≤ 8 kg will receive DPF 5 mg QD for 10 days
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Plasma Concentrations
Time Frame: Days 1, 2, 10, 11, 13 (Groups 1 and 2 only), 15, 18
|
Plasma concentrations (Cmax, tmax, AUC 0-24h, accumulation ratio, apparent terminal elimination half-life, apparent total clearance) of delamanid and its metabolites on Days 1, 2, 10, 11, 13 (Groups 1 and 2 only), 15, 18.
|
Days 1, 2, 10, 11, 13 (Groups 1 and 2 only), 15, 18
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Events
Time Frame: 40 Days
|
Number of reported adverse events
|
40 Days
|
Safety Summary
Time Frame: 40 Days
|
Summary statistics of subjects with clinically significant abnormal laboratory test results, vitals, ECGs
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40 Days
|
Palatability of the Pediatric Formulation
Time Frame: Days 1 and 10
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Palatability of the pediatric formulation will be assessed using an age-appropriate visual hedonic scale and clinical assessment for Groups 3 and 4 only.
|
Days 1 and 10
|
Collaborators and Investigators
Investigators
- Study Director: Jeffrey Hafkin, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 242-12-232
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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