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A 6-Month Safety, Efficacy, and PK Trial of Delamanid in Pediatric Patients With Multidrug Resistant Tuberculosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2016 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01859923
First received: May 15, 2013
Last updated: May 23, 2016
Last verified: May 2016
  Purpose
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 of other anti-tuberculosis drugs in pediatric patients who completed Trial 242-12-232.

Condition Intervention Phase
Multidrug Resistant Tuberculosis
Pediatric
Drug: 100 mg Delamanid
Drug: 50 mg Delamanid
Drug: 25 mg Pediatric Formulation Delamanid
Drug: (Dose to be determined) Pediatric Formulation Delamanid
Drug: Optimized Background Regimen (OBR)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:

Primary Outcome Measures:
  • Safety and Tolerability Summary [ Time Frame: 365 Days ] [ Designated as safety issue: Yes ]
    Safety and tolerability will be assessed by the following variables: physical examination including visual testing and audiometry, vital signs, treatment-emergent adverse events (TEAEs), ECGs and clinical laboratory tests

  • Pharmacokinetics (PK) [ Time Frame: Days 1, 14, 56, 98, 154, 182, 189, 196, 203, 210, 238 ] [ Designated as safety issue: No ]
    Delamanid and metabolite plasma concentrations reported by age and dose group on Days 1, 14, 56, 98, 154, 182, 189, 196, 203, 210, 238.


Secondary Outcome Measures:
  • Pharmacokinetics/Pharmacodynamics (PK/PD) Relationship Analysis of Delamanid and DM-6705 and Change in Corrected QT Interval [ Time Frame: Days 1, 56, 154, 182, and 210 ] [ Designated as safety issue: Yes ]
    ECG and blood samples for PK/PD analysis for changes in QTc as a function of delamanid and DM-6705 plasma concentrations on Days 1, 56, 154, 182, and 210.

  • Efficacy of Delamanid [ Time Frame: 365 Days ] [ Designated as safety issue: Yes ]
    The efficacy of delamanid in treating pediatric MDR-TB patients will be evaluated by chest radiography (patients with pulmonary disease), change in body weight/height, and evaluation of TB symptoms. Sputum culture conversion (for culture-positive patients) will be assessed in patients who are able to produce sputum (or provide other biological specimens) for microbiological evaluation.

  • Palatability of the Pediatric Formulation (Groups 3 and 4 only) [ Time Frame: Days 1, 28, 56, 182 ] [ Designated as safety issue: No ]
    Palatability of the delamanid pediatric formulation will be assessed using an age-appropriate visual hedonic scale and clinical assessment for Groups 3 and 4 only on Days 1, 28, 56, 182.


Estimated Enrollment: 36
Study Start Date: August 2013
Estimated Study Completion Date: November 2019
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: 12 to 17 years of age
100 mg Delamanid BID for 6 months + OBR
Drug: 100 mg Delamanid
100 mg Delamanid BID for 6 months
Other Name: OPC-67683
Drug: Optimized Background Regimen (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 Name: OBR
Experimental: Group 2: 6 to 11 years of age
50 mg Delamanid BID for 6 months + OBR
Drug: 50 mg Delamanid
50 mg Delamanid BID for 6 months
Other Name: OPC-67683
Drug: Optimized Background Regimen (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 Name: OBR
Experimental: Group 3: 3 to 5 years of age
25 mg Pediatric Formulation Delamanid BID for 6 months + OBR
Drug: 25 mg Pediatric Formulation Delamanid
25 mg Pediatric Formulation Delamanid for 6 months
Other Name: DPF
Drug: Optimized Background Regimen (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 Name: OBR
Experimental: Group 4: Birth to 2 years of age
(Dose to be determined) Pediatric Formulation Delamanid BID for 6 months + OBR
Drug: (Dose to be determined) Pediatric Formulation Delamanid
(Dose to be determined) Pediatric Formulation Delamanid
Other Name: DPF
Drug: Optimized Background Regimen (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 Name: OBR

Detailed Description:

This is a phase 2, open-label, multiple-dose, multicenter trial to assess the safety, tolerability, pharmacokinetics, and efficacy of delamanid plus an optimized background regimen in pediatric patients with MDR-TB over a 6-month treatment period. This long-term trial, an extension of Trial 242-12-232, will be conducted in patients who have completed Trial 232.

Enrollment of patients for Groups 1 and 2 is completed. Dosing of patients in Group 4 will be determined after the Trial 232 data is available from at least 6 subjects from Group 3.

  Eligibility

Ages Eligible for Study:   up to 17 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 patients who have reached menarche
  • Written informed consent/assent

Exclusion Criteria:

  • Patients who have not completed Trial 242-12-232
  • Positive test for HIV, previously identified as having HIV, or laboratory evidence of active hepatitis B or C
  • 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 > 3 x 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
  • Lansky Play Performance Score < 50 or Karnofsky Score < 50
  • Administered an 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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01859923

Contacts
Contact: Leesa Gentry 301-728-3160 Leesa.Gentry@otsuka-us.com

Locations
Philippines
De La Salle Health Sciences Institute Recruiting
Dasmariñas City, Cavite, Philippines
Principal Investigator: Melchor VG Frias, MD         
Sub-Investigator: Maria PS Austria-Cantimbuhan, MD         
Sub-Investigator: Hansel JE Ybanez, MD         
Lung Center of the Philippines Recruiting
Quezon City, Metro Manila, Philippines
Principal Investigator: Anjanette Reyes-De Leon, MD         
Sub-Investigator: Maria R Sabangan, MD         
Sub-Investigator: Joan Q Samoy-Tuy, MD         
South Africa
Brooklyn Chest Hospital Recruiting
Ysterplaat, Cape Town, South Africa
Sub-Investigator: Anneke C Hesseling, MD         
Sub-Investigator: Hendrik Scaaf, MD         
Sub-Investigator: Willem Burger, MD         
Sub-Investigator: Marianne Willemse, MD         
Principal Investigator: Anthony Garcia-Prats, MD         
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Jeffrey Hafkin, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

Responsible Party: Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier: NCT01859923     History of Changes
Other Study ID Numbers: 242-12-233 
Study First Received: May 15, 2013
Last Updated: May 23, 2016
Health Authority: United States: Food and Drug Administration
Philippines : Food and Drug Administration
South Africa: Medicines Control Council

Keywords provided by Otsuka Pharmaceutical Development & Commercialization, Inc.:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Infections
Bacterial Infections
Pediatric

Additional relevant MeSH terms:
Tuberculosis
Tuberculosis, Multidrug-Resistant
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on December 09, 2016