Pharmacokinetic and Safety Trial to Determine the Appropriate Dose for Pediatric Patients With Multidrug Resistant Tuberculosis
January 27, 2018 updated by: Otsuka Pharmaceutical Development & Commercialization, Inc.
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
The purpose of this trial is to determine the pediatric dose of delamanid that is equivalent to the adult dose already shown to be effective against multidrug-resistant tuberculosis.
Study Overview
Status
Completed
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
Interventional
Enrollment (Actual)
37
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Cavite
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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
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
No older than 17 years (Child)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
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
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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
|
40 Days
|
|
Palatability of the Pediatric Formulation
Time Frame: Days 1 and 10
|
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
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Jeffrey Hafkin, MD, Otsuka Pharmaceutical Development & Commercialization, Inc.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 14, 2013
Primary Completion (Actual)
December 10, 2017
Study Completion (Actual)
December 28, 2017
Study Registration Dates
First Submitted
May 15, 2013
First Submitted That Met QC Criteria
May 15, 2013
First Posted (Estimate)
May 17, 2013
Study Record Updates
Last Update Posted (Actual)
January 30, 2018
Last Update Submitted That Met QC Criteria
January 27, 2018
Last Verified
January 1, 2018
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 242-12-232
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