Tafenoquine

Study treatments were tafenoquine (150 mg per tablet) (GlaxoSmithKline), dihydroartemisinin-piperaquine tetraphosphate (40 mg/320 mg per tablet) (Eurartesim; Sigma-Tau Industrie Farmaceutiche Riunite SPA), and artemether-lumefantrine (20 mg/120 mg per tablet) (Coartem; Novartis Pharmaceuticals). Subjects were randomized into five cohorts (n = 24 per cohort) to receive tafenoquine on day 1 (300 mg) plus once-daily dihydroartemisinin-piperaquine on days 1, 2, and 3 (120 mg/960 mg for subjects with a body weight of 36 to <75 kg and 160 mg/1,280 mg for subjects with a body weight of ≥75 to 100 kg), or plus artemether-lumefantrine (80 mg/480 mg) with the second dose administered 8 h after the first dose on day 1 and then twice daily on days 2 and 3, or each drug given alone (Fig. 1). No dose adjustments were allowed.

The trial drugs were chloroquine phosphate (300-mg tablets [West Ward Pharmaceuticals] or 150-mg tablets [Alliance Pharmaceuticals]), tafenoquine (150-mg film-coated tablets [GlaxoSmithKline]), and primaquine phosphate (15-mg overencapsulated tablets [Sanofi]) (dosages are given for the free-base form). All patients received 600 mg of open-label chloroquine on days 1 and 2 and 300 mg on day 3. Patients were randomly assigned, in a 2:1 ratio, to receive a single 300-mg dose of tafenoquine while hospitalized on day 1 or 2 or 15 mg of primaquine once daily for 14 days starting on day 1 or 2. All treatments were administered orally with food. To ensure that the patients and investigators were unaware of the trial-group assignments, primaquine-matched placebo was administered to patients in the tafenoquine group and tafenoquine-matched placebo was administered to patients in the primaquine group on the scheduled treatment days. Treatment was discontinued when a patient had a protocol-defined decrease in the hemoglobin level (>3.0 g per deciliter or ≥30% from baseline or to a level of <6.0 g per deciliter), clinically significant changes in the liver chemical profile, a prolongation of the QT interval (corrected with the use of Fridericia’s formula) to more than 500 msec, or a grade 4 adverse event (Table S1 in the Supplementary Appendix, available at NEJM.org).