Project: Evaluation of Pharmacokinetics and Safety/Tolerability of Higher Doses of Rifampicin in Children with Newly Diagnosed, Uncomplicated Tuberculosis

Acronym	Highrif-C (Reference Number: TMA2017CDF-1876)
Duration	01/07/2019 - 30/06/2022
Project Topic	Background: Tuberculosis (TB) treatment outcome is not only challenged by co-morbidities such as HIV infection, but also by insufficient consideration of the relationship between doses of TB drugs administered, concentrations achieved, and eventual desirable and undesirable responses. Especially doses of TB drugs for children are not well substantiated and the concept of higher doses of rifampicin has not been translated to children. Aims and Objectives: This proposal comprises a clinical trial that aims to find the rifampicin dose in children that yields plasma concentrations similar to those achieved in adults after a 35 mg/kg daily dose. This will answer an important scientific question of direct public benefit. In addition, the proposal aims to train the postdoctoral fellow, a PhD student and a Msc student and establishes a pharmacokinetic unit with capacity for drug concentration measurements. Methods: The clinical trial involves a phase IIA dose finding study that will evaluate the pharmacokinetics and safety/tolerability of increasing doses of rifampicin administered for two weeks in consecutive groups of children with TB in the Kilimanjaro region in Tanzania. The postdoctoral fellow will receive hands-on training by working together with the mentor from Radboudumc during all subsequent parts of the study. Skills to perform bio-analysis of TB drugs will be obtained through the pharmacokinetic laboratory at Radboudumc. The fellow will also attend courses on bio-analytical method validation and pharmacokinetic data analysis as well as relevant conferences. All this will enable the development and validation of bio-analytical methods for TB drugs at the Biotechnology Laboratory in the Kilimanjaro region. To achieve sustainability, the fellow will mentor two nextgeneration scientists on the principles of bio-analysis of drugs and pharmacokinetic data analysis through PhD and Master training at the Kilimanjaro Christian Medical University College. This will increase the visibility of the capacity developed and expand the research networks through mentorships and collaboration in the current work and in future projects. Scope and objectives of EDCTP 2: The proposed programme will support the career development of the fellow as an independent researcher who will be capable of initiating and managing her own research programme, focusing on TB as major poverty-related disease. Capacity building includes research technologies that facilitate the conduct of studies as described in the EDCTP business plan of 2014-2024. Expected impacts: The team of experts developed through this proposal will continue to design and conduct pharmacokinetic studies focused on infectious diseases threats in Tanzania and beyond.
Network	EDCTP2
Call	Career Development Fellowships 2017

Project partner

Number	Name	Role	Country
1	The Good Samaritan Foundation, Kilimanjaro Christian Medical Centre	Coordinator	Tanzania