A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)

• Status: Completed
• Trial end date: 2020-01-13
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this trial is to assess the safety, tolerability, pharmacokinetics, and efficacy of long-term (6-month) treatment with delamanid plus an optimized background regimen (OBR) of other anti-tuberculosis drugs in pediatric participants who completed Study 242-12-232 (NCT01856634).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

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

Criteria

Inclusion Criteria:

• Successfully completed Trial 242-12-232

• Confirmed diagnosis of MDR-TB OR

• Presumptive diagnosis of pulmonary or extrapulmonary MDR-TB including one of the following:

• Clinical specimen suggestive of tuberculosis disease

• 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 with a person with known MDR-TB or with 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 participants who have reached menarche

• Written informed consent/assent

Exclusion Criteria:

• Participants who have not completed Trial 242-12-232

• Laboratory evidence of active hepatitis B or C

• Children with body weight < 5.5 kg

• For participants with human-immunodeficiency virus (HIV) co-infection, cluster difference-4 (CD4) cell count ≤ 1000/mm^3 for children 1-5 years old, and ≤ 1500/mm^3 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

• Pre-existing cardiac conditions

• Abnormalities in Screening electrocardiogram (ECG) [including atrio-ventricular (AV) block, blood brain barrier (BBB) or hemi-block, QRS prolongation > 120 milliseconds (ms), or QT interval corrected by Fridericia's formula (QTcF) > 450 ms in both males and females]

• Concomitant condition such as renal impairment characterized by serum creatinine levels > 1.5 mg/dL, hepatic impairment (alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3x upper limit of normal (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 investigational medicinal product (IMP) within 1 month prior to Visit 1 other than delamanid given as IMP in Trial 242-12-232

• Pregnant, breast-feeding, or planning to conceive or father a child within the timeframe described in the informed consent form (Groups 1 and 2 only)