NCT01856634

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jun 2013

Longer than P75 for phase_1

Geographic Reach
2 countries

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 15, 2013

Completed
2 days until next milestone

First Posted

Study publicly available on registry

May 17, 2013

Completed
28 days until next milestone

Study Start

First participant enrolled

June 14, 2013

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 10, 2017

Completed
18 days until next milestone

Study Completion

Last participant's last visit for all outcomes

December 28, 2017

Completed
Last Updated

January 30, 2018

Status Verified

January 1, 2018

Enrollment Period

4.5 years

First QC Date

May 15, 2013

Last Update Submit

January 27, 2018

Conditions

Multidrug Resistant TuberculosisPediatric

Keywords

TuberculosisTuberculosis, Multidrug-ResistantMycobacterium InfectionsActinomycetales InfectionsGram-Positive InfectionsBacterial InfectionsPediatric

Outcome Measures

Primary Outcomes (1)

  • Plasma Concentrations

    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 Outcomes (3)

  • Adverse Events

    40 Days

  • Safety Summary

    40 Days

  • Palatability of the Pediatric Formulation

    Days 1 and 10

Study Arms (4)

Group 1: 12 to 17 years of age

EXPERIMENTAL

Group 1: 100 mg Delamanid BID for 10 days + OBR

Drug: 100 mg DelamanidDrug: Optimized Background Regimen

Group 2: 6 to 11 years of age

EXPERIMENTAL

50 mg Delamanid BID for 10 days + OBR

Drug: 50 mg DelamanidDrug: Optimized Background Regimen

Group 3: 3 to 5 years of age

EXPERIMENTAL

25 mg Pediatric Formulation Delamanid BID for 10 days + OBR

Drug: 25 mg Pediatric Formulation DelamanidDrug: Optimized Background Regimen

Group 4: Birth to 2 years of age

EXPERIMENTAL

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 FormulationDrug: 5 mg Delamanid Pediatric FormulationDrug: Optimized Background Regimen

Interventions

100 mg DelamanidDRUG

100 mg Delamanid BID for 10 days

Also known as: OPC-67683
Group 1: 12 to 17 years of age
50 mg DelamanidDRUG

50 mg Delamanid BID for 10 days

Also known as: OPC-67683
Group 2: 6 to 11 years of age
25 mg Pediatric Formulation DelamanidDRUG

25 mg Pediatric Formulation Delamanid BID for 10 days

Also known as: DPF
Group 3: 3 to 5 years of age
10 mg Delamanid Pediatric FormulationDRUG

Patients \> 10 kg will receive DPF 10 mg BID for 10 days

Also known as: DPF
Group 4: Birth to 2 years of age
5 mg Delamanid Pediatric FormulationDRUG

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

Also known as: DPF
Group 4: Birth to 2 years of age
Optimized Background RegimenDRUG

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

Also known as: OBR
Group 1: 12 to 17 years of ageGroup 2: 6 to 11 years of ageGroup 3: 3 to 5 years of ageGroup 4: Birth to 2 years of age

Eligibility Criteria

AgeUp to 17 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

De La Salle Health Sciences Institute

Dasmariñas, Cavite, 4114, Philippines

Location

Brooklyn Chest Hospital

Ysterplaat, Cape Town, South Africa

Location

Related Publications (1)

  • Garcia-Prats AJ, Frias M, van der Laan L, De Leon A, Gler MT, Schaaf HS, Hesseling AC, Malikaarjun S, Hafkin J. Delamanid Added to an Optimized Background Regimen in Children with Multidrug-Resistant Tuberculosis: Results of a Phase I/II Clinical Trial. Antimicrob Agents Chemother. 2022 May 17;66(5):e0214421. doi: 10.1128/aac.02144-21. Epub 2022 Apr 11.

    PMID: 35404075DERIVED

MeSH Terms

Conditions

Tuberculosis, Multidrug-ResistantTuberculosisMycobacterium InfectionsActinomycetales InfectionsBacterial Infections

Interventions

OPC-67683

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial InfectionsBacterial Infections and MycosesInfections

Study Officials

  • Jeffrey Hafkin, MD

    Otsuka Pharmaceutical Development & Commercialization, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 15, 2013

First Posted

May 17, 2013

Study Start

June 14, 2013

Primary Completion

December 10, 2017

Study Completion

December 28, 2017

Last Updated

January 30, 2018

Record last verified: 2018-01

Locations

PH(1)ZA(1)