Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Pharmacokinetic and Safety Trial to Determine the Appropriate Dose for Pediatric Patients With Multidrug Resistant Tuberculosis

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01856634
First received: May 15, 2013
Last updated: November 7, 2014
Last verified: November 2014
  Purpose

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.


Condition Intervention Phase
Multidrug Resistant Tuberculosis
Pediatric
Drug: 100 mg Delamanid
Drug: 50 mg Delamanid
Phase 1

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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Plasma Concentrations [ Time Frame: Days 1, 2, 10, 11, 13, 15, 18 ] [ Designated as safety issue: No ]
    Plasma concentrations (Cmax, tmax, AUC0-24h, accumulation ratio, apparent terminal elimination half-life, apparent total clearance)of delamanid and its metabolites on Days 1, 2, 10, 11, 13, 15, 18.


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: 40 Days ] [ Designated as safety issue: Yes ]
    Number of Reported Adverse Events

  • Safety Summary [ Time Frame: 40 Days ] [ Designated as safety issue: Yes ]
    Summary Statistics of subjects with clinically significant abnormal laboratory test results, vitals, EGGs


Estimated Enrollment: 12
Study Start Date: July 2013
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Group 1: 12 to 17 years of age
Group 1: 100 mg Delamanid BID for 10 days
Drug: 100 mg Delamanid
100 mg BID for 10 days
Experimental: Group 2: 6 - 11 years of age
50 mg Delamanid BID for 10 days
Drug: 50 mg Delamanid
50 mg BID for 10 days

Detailed Description:

This trial will investigate the pharmacokinetics (PK) and safety of delamanid administered twice daily for 10 days to pediatric patients aged 6 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 two groups:

Group 1: 12 to 17 years (100 mg BID; n=6) Group 2: 6 to 11 years (50 mg BID; n =6)

Dosing of patients in Group 2 will not start until all patients in Group 1 have completed the 18-day Treatment Period (10 days of dosing followed by 8 days of additional PK and safety assessments).

  Eligibility

Ages Eligible for Study:   6 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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: NCT01856634

Locations
Philippines
De La Salle Health Sciences Institute
Dasmariñas City, Cavite, Philippines, 4114
South Africa
Brooklyn Chest Hospital
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: NCT01856634     History of Changes
Other Study ID Numbers: 242-12-232
Study First Received: May 15, 2013
Last Updated: November 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
Actinomycetales Infections
Bacterial Infections
Gram-Positive Bacterial Infections
Mycobacterium Infections

ClinicalTrials.gov processed this record on November 20, 2014