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

• Status: Completed
• Trial end date: 2017-12-28
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Otsuka Pharmaceutical Development & Commercialization, Inc.

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)