Tafenoquine for radical cure of Plasmodium vivax malaria: a multicentre, randomised, double-blind, placebo-controlled phase III trial (“DETECTIVE”).

Background: Tafenoquine (TQ) is an 8-aminoquinoline in development by GlaxoSmithKline and Medicines for Malaria Venture as a single dose treatment for the radical cure of Plasmodium (P.) vivax malaria. Materials and Methods: DETECTIVE (TAF112582, NCT 01376167) was a pivotal phase III trial which recruited participants aged 16-years or older with microscopy-confirmed P. vivax from April 2014 to November 2016. Participants with glucose-6-phosphate dehydrogenase activity less than 70% of the site median by spectrophotometry were excluded. Participants were randomised to placebo, single-dose tafenoquine 300mg, or primaquine (PQ) 15mg daily for 14 days in a ratio of 1:2:1; all participants received chloroquine (CQ). Participants were recruited from eight centres in Brazil, Cambodia, Ethiopia, Peru, the Philippines, and Thailand; the study was approved by the ethics committees governing each site. Clinical and parasitological assessments were made on Days 1–3 (until parasite clearance) and on 10 subsequent visits until day 180. The primary endpoint was relapse-free efficacy at 180 days: the study had >90% power to detect a 30% difference between TQ+CQ and CQ alone. Secondary endpoints included relapse-free efficacy at 4 months, parasite, fever, and gametocyte clearance times. Key safety endpoints included frequency of adverse events, with specific interest in haemoglobin declines (relative fall of >30g/L or ≥30% from baseline, or absolute fall to <60g/L in the first 14 days). Results & conclusions: A total of n=522 (392 male & 130 female) participants were randomised. Unblinded efficacy and safety data will be presented, together with interpretation and conclusions.