The phase II trial for CDA was designed to determine the optimum dose of artesunate to be used in combination with LAPDAP. This open-label study of a fixed-dose of LAPDAP alone plus 1, 2 or 4 mg/kg of artesunate was conducted in Malawi and the Gambia. The trial recruited 116 adults and 107 children with uncomplicated malaria. Patients were randomised into one of four treatment groups and received treatment for three days.

The primary efficacy outcome for the trial was time to reduce baseline parasite levels in the blood by 90 percent. Treatment with CDA, at three doses of artesunate (1, 2 and 4mg/kg) in adults and at two doses (2 and 4mg/kg) in children, led to faster time to reduce parasite levels in the blood by 90 percent when compared to treatment with LAPDAP alone.₁

Treatment with CDA versus LAPDAP alone also demonstrated reductions in the following:

Parasite viability – In adults, there was a statistically significant decrease in parasite viability observed in the 2mg/kg and 4mg/kg artesunate treatment groups versus LAPDAP alone. In children, all artesunate doses significantly reduced the number of viable parasites at 12 hours.

Potential parasite reproductive ability – A dose response effect was noted in the artesunate treatment groups (adults and children) with 2mg/kg and 4mg/kg doses stopping parasite reproductive activity all together.

All treatment doses were generally well tolerated, and the nature and incidence of adverse events were similar across treatment groups.

The phase III programme for CDA consists of two studies which will be conducted across sub-Saharan Africa. The studies will be multi-centre, randomised, double-blind trials utilizing the 4mg/kg artesunate dose. The safety and tolerability of CDA will also be further investigated in the phase III programme, which is expected to begin soon.

This study is expected to enrol 900 subjects aged three months or older with acute uncomplicated P. falciparum malaria. Subjects will be randomised to receive CDA or LAPDAP in a ratio of 2:1 and will receive treatment for three successive days. The study is designed to demonstrate the efficacy of CDA compared to LAPDAP, measured by clearance of the initial malaria infection by Day 7 and remaining free of infection to Day 28. The secondary objective is to demonstrate an advantage of CDA over LAPDAP alone in terms of the proportion of subjects with parasites at 24 hours following the first dose.

This study will compare the efficacy of CDA to Coartem, measured by clearance of the initial malaria infection in 1,395 subjects at least three months of age and up to 14 years of age with acute uncomplicated P. falciparum malaria. Subjects will be randomised to receive CDA or Coartem in a ratio of 2:1 and will receive treatment for three successive days. Coartem is the only fixed-dose ACT currently available for malaria treatment and is therefore considered the standard for comparison. The study is designed to demonstrate the efficacy of CDA compared to Coartem, measured by clearance of the initial malaria infection by Day 7 and remaining free of infection to Day 28. The secondary objectives will compare parasite clearance times and fever reduction times between CDA and Coartem.