Tafenoquine at therapeutic concentrations does not prolong Fridericia-corrected QT interval in healthy subjects.

Tafenoquine is being developed for relapse prevention in Plasmodium vivax malaria. This Phase I, single-blind, randomized, placebo- and active-controlled parallel group study investigated whether tafenoquine at supratherapeutic and therapeutic concentrations prolonged cardiac repolarization in healthy volunteers. Subjects aged 18-65 years were randomized to one of five treatment groups (n=52 per group) to receive placebo, tafenoquine 300, 600, or 1200mg, or moxifloxacin 400mg (positive control). Lack of effect was demonstrated if the upper 90% CI of the change from baseline in QTcF following supratherapeutic tafenoquine 1200mg versus placebo (QTcF) was <10milliseconds for all pre-defined time points. The maximum QTcF with tafenoquine 1200mg (n=50) was 6.39milliseconds (90% CI 2.85, 9.94) at 72hours post-final dose; that is, lack of effect for prolongation of cardiac depolarization was demonstrated. Tafenoquine 300mg (n=48) or 600mg (n=52) had no effect on QTcF. Pharmacokinetic/pharmacodynamic modeling of the tafenoquine-QTcF concentration-effect relationship demonstrated a shallow slope (0.5ms/gmL-1) over a wide concentration range. For moxifloxacin (n=51), maximum QTcF was 8.52milliseconds (90% CI 5.00, 12.04), demonstrating assay sensitivity. In this thorough QT/QTc study, tafenoquine did not have a clinically meaningful effect on cardiac repolarization.