Safety and Efficacy Dose of Artesunate Used in Combination With LAPDAP Treatment of Uncomplicated Falciparum Malaria

An Open, Randomised, Multi-centre Dose Ranging Phase II Study to Evaluate LAPDAP in Combination With Three Different Doses of Artesunate

Drug resistance to a range of antimalarial treatments has become widespread in Africa, South East Asia and South America. Because the rapid spread of drug resistance threatens a public health disaster in these areas of the world and to comply with the WHO-Roll Back Malaria policy of using Artemisinin-based combination therapies (ACT), there is a need to develop new, safe, effective and affordable ACT.

Chlorproguanil-dapsone-artesunate (CDA)is a new ACT that is being developed for the treatment of uncomplicated falciparum malaria in Africa.

Inclusion Criteria:

• Presentation to a healthcare facility with probable uncomplicated clinical malaria
• Adults aged between 18 and 60 years , or children aged between 12 and 120 months
• Weight between 5 and 85kg
• Pure [on microscopic grounds] screening P. falciparum parasitaemia in children from 25,000 to 100,000ul-1, or in adults from 10,000 to 100,000ul-1. [The parasitaemia range for adults was originally set at 25,000 to 100,000µl-1 and changed to 10,000 to 100,000µl-1 in protocol amendment 3 dated 05 May 2004]
• Written or oral witnessed consent obtained from subject, parent or guardian
• Compliance with the requirements of the protocol which include a hospital stay of 4 days and 3 nights and regular blood samples by finger-prick (children) or via a cannula (adults)
• A negative pregnancy test for women of child-bearing age on enrolment

Exclusion Criteria:

• Features of severe/complicated falciparum malaria
• Known allergy to sulphonamides
• Evidence of any concomitant infection at the time of presentation (including P. ovale and P. malaria)
• Any other underlying disease that would compromise the diagnosis and the evaluation of the response to the study medication (including clinical symptoms of immunosuppression, tuberculosis and bacterial infection)
• Treatment in the 28-days prior to screening with sulfadoxine/pyrimethamine (FANSIDAR, CELOXINE), sulfalene/pyrimethamine (METAKELFIN), mefloquine-sulfadoxinepyrimethamine (FANSIMET), chloroquine* (NIVAQUINE); treatment in the 21-days prior to screening with mefloquine, or 7-days prior to screening with amodiaquine, halofantrine, quinine (full course), atovaquone - proguanil, artemisinins, co-artemether, tetracycline or clindamycin, or treatment for 5 half-lives prior to screening with drugs that have a potential anti-malarial activity (e.g. co-trimoxazole in the previous 60 hours)
• Use of an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to screening
• Previous participation in this study
• A positive pregnancy test at enrolment, women of child-bearing age who do not take a pregnancy test or female subjects who are breast-feeding an infant for the duration of the study