. Chlorproguanil Hydrochloride-Dapsone-Artesunate. The Internet Journal of Infectious Diseases. 2004 Volume 4 Number 2.
Worldwide, the World Health Organisation (WHO) estimates that there are 300 million malaria cases annually, directly causing over one million deaths.1 Parasite resistance to anti-malarial treatments is increasing in malaria endemic countries, particularly in Africa. The most frequently used treatments for malaria, such as chloroquine and sulphadoxine/pyrimethamine (S/P), are becoming less and less effective. To tackle drug-resistant malaria, new treatments are urgently needed for the millions affected.
CDA is a new artemisinin-based combination therapy (ACT) of
The World Health Organisation's (WHO) Roll Back Malaria group has made the recommendation that National Malaria Control Programmes (NMCP) use ACT in treatment of uncomplicated malaria in the public sector.
Artemisinin and its derivatives, artemether and artesunate, are plant-derived compounds extracted from
Results of Phase II Trial
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.
Primary Efficacy Outcome
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
Secondary Efficacy Outcomes
Treatment with CDA versus LAPDAP alone also demonstrated reductions in the following:
All treatment doses were generally well tolerated, and the nature and incidence of adverse events were similar across treatment groups.
Phase III CDA Trials
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.
CDA vs. LAPDAP Study
This study is expected to enrol 900 subjects aged three months or older with acute uncomplicated
CDA vs. Coartem® (artemether–lumefantrine) Study
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
CDA is being developed by a public-private partnership (PPP) between GlaxoSmithKline (GSK), WHO/TDR (Tropical Disease Research Programme of the World Health Organization) and the Medicines for Malaria Venture (MMV). Academic partners in its development are the University of Liverpool, Liverpool School of Tropical Medicine and the London School of Hygiene and Tropical Medicine. If the development of CDA is successful, it will be supplied at sustainable, preferential prices to the public sector in malaria-endemic countries in Africa to maximise availability to those in need. CDA is expected to be available in 2008 as a convenient once-daily dose.
The partnership has already successfully developed LAPDAP, a combination therapy containing two well established antimalarial agents, chlorproguanil and dapsone, which act synergistically.
GSK is committed to PPPs which offer an innovative approach to creating safe, effective and affordable medicines for the developing world. GSK plays a leading role in the research and development of these medicines. CDA is part of GSK's sustained and long-term commitment to fighting malaria.
Coartem® is a registered trademark of the Novartis Group, Novartis International AG