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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 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: April 7, 2014
Last verified: April 2014
  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 of other anti-tuberculosis drugs in pediatric patients who completed Trial 242-12-232.


Condition Intervention Phase
Multidrug Resistant Tuberculosis
Pediatric
Drug: Delamanid
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:
  • Adverse Events [ Time Frame: 12 Months ] [ Designated as safety issue: Yes ]
    Number of Subjects reporting an Adverse Event

  • Safety Summary [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Summary Statistics of subjects with clinically significant abnormal laboratory test results, vitals, EGGs and Physical Examinations

  • Pharmacokinetics [ Time Frame: Day 1 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) on Day 1

  • Pharmacokinetics [ Time Frame: Day 56 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) on Day 56

  • Pharmacokinetics [ Time Frame: Day 154 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) on Day 154

  • Pharmacokinetics [ Time Frame: Day 182 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) on Day 182

  • Pharmacokinetics [ Time Frame: Day 210 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) on Day 210 at the theoretical predose time when delamanid would have been administered

  • Pharmacokinetics [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 14

  • Pharmacokinetics [ Time Frame: Day 98 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 98

  • Pharmacokinetics [ Time Frame: Day 189 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 189

  • Pharmacokinetics [ Time Frame: Day 196 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 196

  • Pharmacokinetics [ Time Frame: Day 203 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 203

  • Pharmacokinetics [ Time Frame: Day 238 ] [ Designated as safety issue: No ]
    Delamanid and plasma concentrations predose (0 hours) at any time point on Day 238


Secondary Outcome Measures:
  • Pharmacokinetics/pharmacodynamics [ Time Frame: 365 Days ] [ Designated as safety issue: Yes ]
    DM-6705 plasma concentrations and changes in QTc interval using the paired pharmacokinetic/pharmacodynamic assessments on Days 1, 56, 154, 182, and 210.

  • Resolution of TB Symptoms [ Time Frame: 365 Days ] [ Designated as safety issue: Yes ]
    Proportion of subjects with resolution of TB symptoms based on investigator evaluation.


Estimated Enrollment: 12
Study Start Date: August 2013
Estimated Study Completion Date: April 2017
Estimated Primary Completion Date: March 2017 (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
Drug: Delamanid
Other Name: OPC-67683
Experimental: Group 2: 6 to 11 years of age
50 mg Delamanid BID for 6 months
Drug: Delamanid
Other Name: OPC-67683

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. Trial 242-12-233 will initially be conducted sequentially in two groups of pediatric patients by age group: Group 1 (ages 12 to 17 years) and Group 2 (ages 6 to 11 years).

Younger age groups (Group 3, [3 to 5 years] and Group 4, [0 to 2 years]) will be enrolled when the pediatric formulation becomes available. Details describing Groups 3 and 4 will be included in an amendment to the protocol.

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
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 MDR TB including one of the following:

    • Persistent cough lasting > 2 weeks
    • Fever, weight loss, and failure to thrive
    • Chest radiograph consistent with TB
    • Sputum smear positive for acid-fast bacilli 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:

  • 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
  • Rifampicin and/or moxifloxacin within 1 week prior to the first dose of delamanid
  • Lansky Play Performance Score < 50 or Karnofsky Score < 50
  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: Corey Best, MBA 919-544-8143 corey.best@otsuka-us.com

Locations
Philippines
De La Salle Health Sciences Institute Recruiting
Dasmariñas City, Cavite, Philippines
Lung Center of the Philippines Recruiting
Quezon City, Metro Manila, Philippines
South Africa
Brooklyn Chest Hospital Recruiting
Ysterplaat, Cape Town, South Africa
Sponsors and Collaborators
Otsuka Pharmaceutical Development & Commercialization, Inc.
Investigators
Study Director: Jeffrey Hafkin, MD Otsuka Pharmaceutical Development & Commercialization, Inc.
  More Information

No publications provided

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: April 7, 2014
Health Authority: United States: Food and Drug Administration

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 September 16, 2014