Efficacy, safety and population pharmacokinetics of artesunate-mefloquine combination for the treatment of uncomplicated falciparum malaria in African children versus artemether-lumefantrine

INTERVENTION: All patients recruited into the study will be given full, supervised treatment with either: 1. Artesunate‐mefloquine (ASMQ) co‐formulation (25/55 mg), administered orally for 3 consecutive days according to the following dosing schedule: 1.1. 6 to 11 months a single tablet once daily 1.2. 12 to 59 months of age, 2 tablets once daily 2. Artemether‐lumefantrine (AM‐LM) (Coartem® dispersible, Novartis Pharma), 6 doses at 0, 8, 24, 36, 48 and 60 hours will be administered orally to patients. Doses will be as follows: 2.1. 5 to less than 15 kg body weight (BW): 1 tablet at inclusion, again 8 hours later and then twice daily on each of the following 2 days (total course comprises 6 tablets) 2.2. 15 to less than 25 kg BW: 2 tablets at inclusion, again 8 hours later and then twice daily on each of the following 2 days (total course comprises 12 tablets) Total duration: 3 days of treatment and 60 follow‐up days. CONDITION: Malaria ; Infections and Infestations ; Malaria PRIMARY OUTCOME: Cure rate as determined by polymer chain reaction (PCR)‐corrected adequate clinical and parasitological response (ACPR) on Day 63. Treatment success or failures will be classified according to WHO Guidelines 2003. SECONDARY OUTCOME: 1. Safety, measured on day 0, 1, 2, 3, 4, 7, 14, 21, 28, 35, 42, 49, 56, 63:; 1.1. Frequency of adverse events by intervention; 1.2. Detailed description of time course and vomiting frequency; 1.3. Frequency of serious adverse events and adverse events leading to treatment discontinuation by intervention; 2. Pharmacokinetics: population pharmacokinetic parameters for artesunate (AS), its main metabolite, dihydroartemisinin (DHA), mefloquine (MQ) and lumefantrine in a sub‐set of 50 randomly selected patients. Drug levels for MQ and lumefantrine will be obtained for all patients on day 0 and day 7 and correlated with clinical response. Measured on day 0, 2, 3, 7, 28, 35, 42, 49, 56, 63.; ; Furthermore, for all patients with recurrence of parasitemia, a blood sample will be collected on the day of failure, in order to know the drug level at that specific time point. INCLUSION CRITERIA: 1. Aged between 6 to 59 months, either sex 2. Presence of acute uncomplicated P. falciparum mono‐infection confirmed by: 2.1. Axillary temperature greater than 37.5°C, and 2.2. Positive microscopy of P. falciparum with parasite density between 2,000 and 200,000 asexual parasites/µl 3. Written informed consent from parent/guardian