Pharmacokinetic and Safety Trial to Determine the Appropriate Dose for Pediatric Patients With Multidrug Resistant Tuberculosis
Multidrug Resistant Tuberculosis, Pediatric
About this trial
This is an interventional treatment trial for Multidrug Resistant Tuberculosis focused on measuring Tuberculosis, Tuberculosis, Multidrug-Resistant, Mycobacterium Infections, Actinomycetales Infections, Gram-Positive Infections, Bacterial Infections, Pediatric
Eligibility 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)
Sites / Locations
- De La Salle Health Sciences Institute
- Brooklyn Chest Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Group 1: 12 to 17 years of age
Group 2: 6 to 11 years of age
Group 3: 3 to 5 years of age
Group 4: Birth to 2 years of age
Group 1: 100 mg Delamanid BID for 10 days + OBR
50 mg Delamanid BID for 10 days + OBR
25 mg Pediatric Formulation Delamanid BID for 10 days + OBR
Delamanid 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