Procedures
malaria
MALARIA, BLOOD, RELAPSE
Study treatments were supplied by the sponsor as eurartesim tablets containing dihydroartemisinin 40 mg and piperaquine 320 mg (Alfasigma, Bologna, Italy), tafenoquine 150-mg tablets (GSK, London, UK), and primaquine formulated as over-encapsulated 15-mg tablets (Sanofi-Aventis, Bridgewater, NJ, USA). All patients received open-label, oral dihydroartemisinin–piperaquine daily over 3 consecutive days (days 1–3), according to weight (three tablets <75 kg or four tablets ≥75 kg). Tafenoquine (or matched placebo) was given as a single oral 300-mg dose (two × 150-mg tablets) on either day 1 or day 2. Primaquine (or matched primaquine placebo) was administered as a single oral 15-mg daily dose for 14 consecutive days starting on day 1 or day 2. All study medications were administered under direct supervision by study staff in the clinic.Following informed consent, screening assessments were done and all patients who were eligible to receive dihydroartemisinin–piperaquine on the basis of labelling received their first dose of dihydroartemisinin–piperaquine at least 3 h after their last meal. Once laboratory results confirmed continued eligibility, patients were randomly assigned to masked study medication, with the first dose given, with food, at least 3 h after dihydroartemisinin–piperaquine, on day 1 or day 2. Blood smears for parasite assessment were done twice daily until two consecutive negative smears were obtained. After completion of the dosing period, patients attended a further seven follow-up visits (on days 21, 28, 60, 90, 120, 150, and 180).Patients were evaluated by clinical assessments and laboratory investigations including Giemsa-stained blood smears for parasitology, 12-lead electrocardiograms, haematology and clinical chemistry tests, and methaemoglobin measurement by means of a non-invasive pulse oximeter (Masimo, Irvine, CA, USA) at screening and selected visits throughout the study. After their initial in-patient treatments, patients were instructed to promptly return to the clinic (open 24 h) if they had malaria symptoms. Patients who returned with Blood samples were taken for tafenoquine pharmacokinetic analysis, cytochrome P-450 2D6 (CYP2D6) genotyping and parasite microsatellite DNA analysis (to establish the proportion of heterologous and homologous relapses). Relapse was defined as genetically homologous when All patients who were relapse free at 6 months received high-dose open-label primaquine (ie, 0·5 mg/kg daily) for 14 days at the end of the study to minimise the likelihood of relapse.