A 6-Month Safety, Efficacy, and Pharmacokinetic (PK) Trial of Delamanid in Pediatric Participants With Multidrug Resistant Tuberculosis (MDR-TB)
Condition: Multidrug Resistant Tuberculosis
MeSH terms: Tuberculosis; Tuberculosis, Multidrug-Resistant
Intervention: Delamanid; Delamanid Pediatric Formulation (DPF); Optimized Background Regimen (OBR)
Intervention description: Participants received adult formulation delamanid as per regimen specified in the arm description. Morning dose of the delamanid BID regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard dinner meal.; Participants received delamanid as an extemporaneous suspension using the delamanid pediatric dispersible tablet formulation. Morning dose of the delamanid BID/once daily (QD) regimen was given within 30 minutes after the start of a standard breakfast meal. The evening dose of the BID dose regimen was given 10 hours post morning dose and within 30 minutes after the start of a standard meal.; Selection and administration of the treatment medications (i.e. OBRs) was based on Search Results Web result with site links
World Health Organization (WHO's) Guidelines for the programmatic management of drug-resistant TB, in conjunction with national TB program guidelines. Study Investigator could change OBR for a participant based on his/her tolerability and drug susceptibility testing (DST) results.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 37.0
Sex: All
Minimum age: 0 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Tuberculosis; Tuberculosis, Multidrug-Resistant; Mycobacterium Infections; Actinomycetes Infections; Gram-Positive Infections; Bacterial Infections; Pediatric

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).
    

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)