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Multidrug Resistant TuberculosisPhase 1NCT01856634

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

A Phase 1 study testing 100 mg Delamanid, 50 mg Delamanid and 25 mg Pediatric Formulation Delamanid in people with Multidrug Resistant Tuberculosis and Pediatric, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages Up to 17 years
Conditions the study is for
Multidrug Resistant Tuberculosis, Pediatric
What is being tested?
100 mg Delamanid, 50 mg Delamanid and 25 mg Pediatric Formulation Delamanid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
2 sitesin 2 countries
Study dates
14 Jun 2013to 28 Dec 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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)

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Philippines1 site

  • De La Salle Health Sciences Institute

    Dasmariñas, Cavite, 4114

Other trials in Philippines

South Africa1 site

  • Brooklyn Chest Hospital

    Ysterplaat, Cape Town

Other trials in South Africa

About this study

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

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.

Read the 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
Being tested
100 mg Delamanid, 50 mg Delamanid, 25 mg Pediatric Formulation Delamanid, 10 mg Delamanid Pediatric Formulation, 5 mg Delamanid Pediatric Formulation
Keywords
Tuberculosis, Tuberculosis, Multidrug-Resistant, Mycobacterium Infections, Actinomycetales Infections, Gram-Positive Infections, Bacterial Infections, Pediatric
Medical subject headings
Tuberculosis, Multidrug-Resistant, Tuberculosis, Mycobacterium Infections, Actinomycetales Infections, Bacterial Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 100 mg DelamanidDrug

    Also called OPC-67683

    100 mg Delamanid BID for 10 days

  • 50 mg DelamanidDrug

    Also called OPC-67683

    50 mg Delamanid BID for 10 days

  • 25 mg Pediatric Formulation DelamanidDrug

    Also called DPF

    25 mg Pediatric Formulation Delamanid BID for 10 days

  • 10 mg Delamanid Pediatric FormulationDrug

    Also called DPF

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

  • 5 mg Delamanid Pediatric FormulationDrug

    Also called DPF

    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

  • Optimized Background RegimenDrug

    Also called 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

Study groups in NCT01856634
Study groupRoleWhat they receive
Group 1: 12 to 17 years of ageExperimentalGroup 1: 100 mg Delamanid BID for 10 days + OBR
Receives: Drug: 100 mg Delamanid; Drug: Optimized Background Regimen
Group 2: 6 to 11 years of ageExperimental50 mg Delamanid BID for 10 days + OBR
Receives: Drug: 50 mg Delamanid; Drug: Optimized Background Regimen
Group 3: 3 to 5 years of ageExperimental25 mg Pediatric Formulation Delamanid BID for 10 days + OBR
Receives: Drug: 25 mg Pediatric Formulation Delamanid; Drug: Optimized Background Regimen
Group 4: Birth to 2 years of ageExperimentalDelamanid 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
Receives: Drug: 10 mg Delamanid Pediatric Formulation; Drug: 5 mg Delamanid Pediatric Formulation; Drug: Optimized Background Regimen

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Days 1, 2, 10, 11, 13 (Groups 1 and 2 only), 15, 18

Secondary outcomes (3)

  1. Adverse Events

    Number of reported adverse events

    Measured: 40 Days

  2. Safety Summary

    Summary statistics of subjects with clinically significant abnormal laboratory test results, vitals, ECGs

    Measured: 40 Days

  3. Palatability of the Pediatric Formulation

    Palatability of the pediatric formulation will be assessed using an age-appropriate visual hedonic scale and clinical assessment for Groups 3 and 4 only.

    Measured: Days 1 and 10

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 May 2013 (estimated)
  2. Study start14 Jun 2013
  3. Primary completion10 Dec 2017
  4. Study completion28 Dec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01856634
Sponsor's protocol ID
242-12-232
Status last verified
Jan 2018
First submitted
15 May 2013
Last updated
30 Jan 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 35404075

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing 100 mg Delamanid, 50 mg Delamanid and 25 mg Pediatric Formulation Delamanid in people with Multidrug Resistant Tuberculosis and Pediatric, run by Otsuka Pharmaceutical Development & Commercialization, Inc. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Philippines, South Africa. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Plasma Concentrations (time frame: Days 1, 2, 10, 11, 13 (Groups 1 and 2 only), 15, 18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01856634, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2018.

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