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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2017 by Otsuka Pharmaceutical Development & Commercialization, Inc.
Sponsor:
Information provided by (Responsible Party):
Otsuka Pharmaceutical Development & Commercialization, Inc.
ClinicalTrials.gov Identifier:
NCT01856634
First received: May 15, 2013
Last updated: March 10, 2017
Last verified: March 2017
  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
Drug: 25 mg Pediatric Formulation Delamanid
Drug: 10 mg Delamanid Pediatric Formulation
Drug: 5 mg Delamanid Pediatric Formulation
Drug: Optimized Background Regimen
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
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 (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.


Secondary Outcome Measures:
  • Adverse Events [ Time Frame: 40 Days ]
    Number of reported adverse events

  • Safety Summary [ Time Frame: 40 Days ]
    Summary statistics of subjects with clinically significant abnormal laboratory test results, vitals, ECGs

  • 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.


Estimated Enrollment: 36
Study Start Date: July 2013
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (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 + OBR
Drug: 100 mg Delamanid
100 mg Delamanid BID for 10 days
Other Name: OPC-67683
Drug: Optimized Background Regimen
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 10 days + OBR
Drug: 50 mg Delamanid
50 mg Delamanid BID for 10 days
Other Name: OPC-67683
Drug: Optimized Background Regimen
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 10 days + OBR
Drug: 25 mg Pediatric Formulation Delamanid
25 mg Pediatric Formulation Delamanid BID for 10 days
Other Name: DPF
Drug: Optimized Background Regimen
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

Delamanid Pediatric Formulation (DPF) for 10 days + OBR. DPF dose based on patient's body weight during baseline visit:

  • Patient's > 10 kg will receive DPF 10 mg BID + OBR
  • Patient's > 8 kg and ≤ 10 kg will receive DPF 5 mg BID + OBR
  • Patients ≤ 8 kg will receive DPF 5 mg QD + OBR
Drug: 10 mg Delamanid Pediatric Formulation
Patients > 10 kg will receive DPF 10 mg BID for 10 days
Other Name: DPF
Drug: 5 mg Delamanid Pediatric Formulation

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 Name: DPF
Drug: Optimized Background Regimen
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 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

Enrollment is complete for patients in Groups 1, 2 and 3.

  Eligibility

Ages Eligible for Study:   up to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  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

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, 4114
Principal Investigator: Melchor VG Frias, IV, MD         
Sub-Investigator: Maria P Austria-Cantimbuhan, MD         
Sub-Investigator: Hansel JE Ybanez, MD         
Sub-Investigator: Kristine Latorre-Mendoza, MD         
Sub-Investigator: Ana J Vazquez-Genuino, MD         
South Africa
Brooklyn Chest Hospital Recruiting
Ysterplaat, Cape Town, South Africa
Principal Investigator: Anthony Garcia-Prats, MD         
Sub-Investigator: Anneke C Hesseling, MD         
Sub-Investigator: Willem Burger, MD         
Sub-Investigator: Marianne Willemse, MD         
Sub-Investigator: Hendrik Schaaf, 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: NCT01856634     History of Changes
Other Study ID Numbers: 242-12-232
Study First Received: May 15, 2013
Last Updated: March 10, 2017

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 May 25, 2017