a 6-month safety, efficacy, and pharmacokinetic (pk) trial of delamanid in pediatric participants with multidrug resistant tuberculosis (mdr-tb)

Conditions: Multidrug Resistant Tuberculosis

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).

this study will assess the safety, tolerability, pharmacokinetics, and efficacy of delamanid plus an optimized background regimen in pediatric participants with mdr-tb over a 6-month treatment period. this long-term study, an extension of study 242-12-232, will be conducted in participants who have completed study 242-12-232.

Eligibility 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)

Keywords: tuberculosis tuberculosis, multidrug-resistant mycobacterium infections actinomycetes infections gram-positive infections bacterial infections pediatric