Health Condition 1: A199- Miliary tuberculosis, unspecified Health Condition 2: A159- Respiratory tuberculosis unspecified Health Condition 3: A188- Tuberculosis of other specified organs
Conditions
Interventions
Intervention1: Clofazimine and moxifloxacin: Children will receive study formulations of these drugs as part of (not in addition to) their optimized routine RR-TB treatment regimen.
The interventiona
Sponsors
Stellenbosch University
Eligibility
Inclusion criteria
Inclusion criteria: 1. Confirmed or clinically diagnosed pulmonary or extrapulmonary RR-TB 2. Routinely treated with both clofazimine and a fluoroquinolone as part of a RR-TB treatment regimen and on treatment for 3. HIV-infected and -uninfected 4. Written informed consent (and assent in older children)
Exclusion criteria
Exclusion criteria: 1. Hemoglobin 2. ALT > 5X the upper limit of normal (ULN) at the time of enrolment 3. Body weight 4. QTcF >460 ms (value of QT interval, corrected using Fridericaâ??s method) on ECG during screening, history of familial long QT syndrome, or any other clinically significant cardiac or ECG abnormality that the investigator deems may be a risk for QT prolongation Note: Participants must be enrolled into the study based on final ECG readings by the protocol cardiologist. The site investigator should also evaluate the ECG and document that assessment in the source documentation and manage the participant clinically in real time based on the local reading 5. Known intolerance or hypersensitivity to moxifloxacin or clofazimine 6. A condition such as clinically significant cardiac, renal, liver, neurological, neuropsyschological or any other condition that in the opinion of the site 7. Use, or anticipated use, of any of the prohibited medications (see Section 5.7) within 3 days of enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| PKparameters (clearance,volume of distribution,and absorption-related parameters,and AUC, Cmax) of moxifloxacin and clofazimine in children with RR-TB, for the whole group and by age categories (0-2, 2-5and 5-12 years) and weight bands (above and below 15 kg) per formulation (i.e. PK sampling occasion).Timepoint: Measured through Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Descriptive summaries and qualitative descriptions of acceptability (including palatability) of treatment regimens and moxifloxacin and clofazimine formulations relative to patient and caregiver social contextsTimepoint: Measured through Week 24;Direct and indirect health system and household costs associated with treatment of RR-TBTimepoint: Measured through Week 24;Dosing algorithm derived by simulation of optimal moxifloxacin and clofazimine doses in children, using nonlinear mixed effects models, and an age and/or weight banding approach.Timepoint: Measured through Week 24;Plasma PK parameters of moxifloxacin and clofazimine in children routinely treated for RR-TBbyage, weight,nutriotional status(WAZ andHAZ), formulation andother key covariatesTimepoint: Measured through Week 24;Safety and tolerability endpoints (Cumulative incidence of AEs of any grade using DAIDS tables for grading the severity of adverse events, Cumulative incidence of â?¥ Grade 3 AEs, Cumulative incidence of QT interval prolongation and change in QTcF (ms) )Timepoint: Measured through Week 24 | — |
Countries
India, Philippines, South Africa
Contacts
Public ContactDr Aarti Kinikar
BJGMC and Sassoon General Hospitals
Outcome results
None listed