The Developing Paediatric Primaquine project will develop and prequalify primaquine in tablet strengths appropriate for children and develop optimal primaquine regimens so that one tablet equals one dose.
Primaquine has two key roles in malaria elimination: the radical cure of Plasmodium vivax and P. ovale, and blocking P. falciparum transmission. DPP’s research includes granule work, taste masking, a bioequivalence study and two field trials: one of vivax radical cure (Ethiopia) and a study of single low dose primaquine to block falciparum malaria transmission (Burkina Faso).
Although children aged under 5 years are the most vulnerable group affected by malaria, accounting for 67% (274,000) of all malaria deaths worldwide in 2019, there are currently no paediatric primaquine tablets or kids-friendly formulations approved by a stringent regulatory authority or prequalified by WHO. This is a major obstacle for global malaria elimination – particularly in Africa, home to 94% of malaria cases and deaths, but also countries with high burdens of P. vivax.
Supported by a grant from EDCTP2 (the European and Developing Countries Clinical Trials Partnership), an African-European institutional consortium, the Developing Paediatric Primaquine (DPP) project will develop and prequalify primaquine in a range of tablet strengths appropriate for children (2.5, 3.75, and scored 5, 7.5 and 15 mg) and develop optimal primaquine regimens so that one tablet equals one dose.
Once the bioequivalence of the 15 mg generic tablet is confirmed and the biowaiver for the lower strengths is granted, the full range of primaquine tablets can be prequalified – permitting their use by national malaria control programmes – with potentially a big impact on global malaria.
“Getting these child-appropriate primaquine doses prequalified by the WHO could have a massive impact on malaria elimination and malaria deaths in African children. WHO prequalification would allow the child-appropriate doses to be distributed widely by malaria control programmes,” explained project coordinator Dr Bob Taylor of the Mahidol Oxford Tropical Medicine Research Unit (MORU).
To optimise the drug formulations and make the pills palatable to children, the DPP project will perform sensory studies to identify the best kid-friendly aromas to mask the bitter taste of primaquine and, in parallel, validate the use of these new tablets by conducting clinical and pharmacokinetic studies for curing P. vivax in Ethiopia and blocking the transmission of P. falciparum malaria in Burkina Faso. Moreover, granule formulations and bespoke packaging are new concepts that will also be developed to make primaquine more user-friendly and so improve adherence.
“Granules are really the most convenient form for small children, and we hope to obtain additional funds in anticipation that the WHO will call officially for primaquine granules. In the meantime, packaging flavoured primaquine tablets for children is the way to go,” said DPP project manager Dr Julie Nguyen Ngoc Pouplin, who is based at Réseau Médicaments et Développement (ReMeD).
On Sunday 25 April, World Malaria Day, the Developing Paediatric Primaquine project will launch its website. Intended for a broad audience, including malariologists, policy makers, regulatory authorities and curious members of the public, the site will present the DPP project roadmap, its different work packages and consortium partners, and provide updates on project progress.
The Developing Paediatric Primaquine project is part of the EDCTP2 programme supported by the European Union