This proposal aims at the fast-track pharmaceutical development and clinical
validation of two artesunate-based fixed dose combinations for the treatment of
malaria, including the preparation of relevant registration files. The goal is
to make these new combination drugs available for use as quality, safe, viable,
adapted and affordable drugs in the endemic countries. This project contributes
a missing link in promoting antimalarial policy changes towards combination
therapy, and the successful implementation thereof. It builds upon the expertise
of R&D centres in the EU and different regions in the world, which are being
mobilised in an international effort to improve dramatically the available
malaria treatment tools.
Clinical trials and therapeutic experience have indicated that combinations
of antimalarial drugs with different mechanisms of action, including artemisinin
derivatives, improve therapy by preventing resistance. The success of the
deployment of such drug combinations depends upon the availability of affordable
fixed-dose combinations, adapted to the conditions of use. The proposal aims at
promoting a therapeutic antimalarial policy change and the successful
implementation thereof, by completing the development of quality, effective,
safe, adapted and affordable fixed dose combinations of artesunate+mefloquine
and artesunate+amodiaquine respectively. This will include preparing
registration files and making the combination drug products available in the
endemic countries by means of an international co-operation involving experts
and institutes of the concerned countries.
The work will include six different types of activities:
1) Pre-clinical pharmaceutical development of the two fixed dose combination
products (artesunate+mefloquine and artesunate+amodiaquine) for the generation
of the Chemistry, Manufacturing and Control Sections (CMC) for the registration
file and manufacturing of clinical batches. This will involve analytical and
pharmaceutical sciences contributions.
2) Pre-clinical biological development and assessment, including a safety
section (acute and adapted chronic administration) and a ‘mechanism of action’
contribution. This will require the development of adapted bioanalytical methods
and conducting toxicokinetics studies in two animal species.
3) Clinical confirmation trials with the new formulations complementing
existing data. This will also include an investigation of the bioavailability of
the new combination.
4) Compilation of a registration documentation file, which can be submitted
in the various malaria endemic countries.
5) Coordination of the work performed in different countries and regions.
6) Involvement in reviews and case studies with experts and authorities of
the countries in which the new formulation will be developed and registered.
Year 1: Definition of the new formulations and scale-up of production.
Pre-clinical safety and pharmacological data. Bioavailability of new
Year 2: Start of clinical studies. Identification of a manufacturing
Year 3: Clinical validation data. Stability analysis and reports.
Registration of the new formulations.
Fondation Médecins sans Frontières
Access to Essential Medicines
Tel: +33 1 64 92 20 65
Fax: +33 1 64 92 20 65
- Université Victor Segalen Bordeaux 2 - Cellule de Valorisation, FR-Bordeaux, France
- University of Oxford - Centre for Tropical Medicine, Nuffield, Department of Medicine, UK-Oxford, United Kingdom
- Universiti Sains Malaysia - Centre for Drug Research, Pulau Pinang, Malaysia
- Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand
- Instituto de Tecnologia Am Farmacos: Far-Manguinhos - Department of Pharmacotechnics / Far-Manguinhos: Fiocruz, Rio de Janeiro, Brazil
- World Health Organisation - UNDP/World Bank/ WHO Special Programme for Research and Training in Tropical Diseases (TDR), Geneva, Switzerland
- Centre National de Recherche et de Formation sur le Paludisme – Cnre, Burkina Faso