The Pharmacokinetics, Safety and Acceptability of New Child-Friendly Formulations of Clofazimine and Moxifloxacin in Children Routinely Treated for Rifampicin-Resistant Tuberculosis (CATALYST)

PK, safety and acceptability data and practical guidance on the optimal dosing of new more child-friendly formulations of moxifloxacin and clofazimine in children are urgently needed to inform their current and future use in children with Rifampicin-Resistant TB (RR-TB).  Both medications have a key role in the RR-TB treatment regimens currently recommended by the WHO and in novel TB regimens being evaluated in trials in children and adults.  Based on the critical knowledge gaps described above, we propose to investigate the PK, safety, tolerability and acceptability of moxifloxacin and clofazimine, including the effect of formulation type, in HIV-infected and uninfected children aged 0 to <15 years routinely treated for RR-TB.  This is an open-label multisite trial to study the PK, safety, tolerability, and acceptability of new child-friendly formulations of moxifloxacin and clofazimine (hereafter referred to as “study drugs”) given at current WHO-recommend weight-based doses, where these drugs are included in an optimized RR-TB treatment regimen, in HIV-infected and -uninfected children treated for RR-TB.

Study Objectives 
In HIV-infected and -uninfected children <15 years of age routinely treated for RR-TB:
Primary 
To characterize the PK of moxifloxacin and clofazimine, including differences in absorption-related parameters (bioavailability and rate of absorption) by formulation type
Secondary
To characterize the safety and tolerability of new child-friendly moxifloxacin and clofazimine formulations (“study drugs”)
To characterize the impact of age, weight, nutritional status, and other key covariates on moxifloxacin and clofazimine pharmacokinetics, by formulation type

To determine the moxifloxacin and clofazimine weight-banded dosing algorithms for the new child-friendly formulations that achieve similar exposure (AUC) and concentration-time profile in children compared to adults receiving current standard WHO-recommended doses
To characterize the acceptability, including palatability, of the new child-friendly moxifloxacin and clofazimine formulations among children and their caregivers
To describe the costs (both direct and indirect health system and household costs) of treatment of RR-TB in general, and calculate optimal prices ranges for provision of the new childnew child-friendly moxifloxacin and clofazimine formulations specifically, at scale in routine care