Lack of effect of favipiravir, a novel antiviral agent, on the QT interval in healthy Japanese adults

Objective: A thorough QT study of favipiravir, a novel antiviral agent, was conducted using a randomized, double-blind, 4-group, 4-period crossover, placebo and positive-controlled (open-label moxifloxacin) design. Materials and methods: 56 healthy Japanese adults of both sexes received single oral doses of favipiravir 1,200 and 2,400 mg (Avigan (R) Tablets, Toyama Chemical Co., Ltd.), moxifloxacin 400 mg, and a placebo. QT intervals after these treatments were measured under blinded conditions. The primary endpoint was the time-matched, placebo-adjusted change in corrected QT intervals using the Fridericia method (QTcF) from predose for favipiravir or moxifloxacin (Delta Delta QTcF). Results: Lower bounds of the two-sided 90% confidence interval of Delta Delta QTcF values for moxifloxacin exceeded 3 msec at all time points, and the maximum value was 14.0 (11.8 - 16.1, 90% confidence interval) msec at 3 hours after administration. Similarly, maximum Delta Delta QTcF values for favipiravir were 0.833 (-1.33 - 3.00) msec at 3 hours after administration of 1,200 mg, and 0.500 (-1.88 - 2.88) msec at 6 hours after administration of 2,400 mg. Calculation of the sample size using the Delta Delta QTcF value of moxifloxacin indicated that 25 subjects would be sufficient for detection at a power of 90% or higher, which meets the criteria for assuring assay sensitivity. Conclusions: It is possible to use a smaller number of subjects in thorough QT studies in Japan than in Europe and the US utilizing moxifloxacin as a positive control. There were no detectable effects of favipiravir on the QT/QTc interval.