Favipiravir at single oral doses of 1,200 and 2,400 mg had no detectable effect on the QT/QTc interval in healthy Japanese adults, with maximum placebo-adjusted QTcF changes of 0.833 and 0.500 msec.
RCT (n=56)
Double-blind
4-group, 4-period crossover
Does favipiravir prolong the QT interval in healthy Japanese adults?
Favipiravir at single doses up to 2,400 mg does not prolong the QT interval in healthy adults.
Effect estimate: max ΔΔQTcF 0.833 msec (95% CI -1.33-3.00)
Absolute Event Rate: 0.833% vs 14%
OBJECTIVE: A thorough QT study of favipiravir, a novel antiviral agent, was conducted using a randomized, doubleblind, 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® 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 (ΔΔQTcF). RESULTS: Lower bounds of the two-sided 90% confidence interval of ΔΔQTcF 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 ΔΔQTcF 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 ΔΔQTcF 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.
Kumagai et al. (Wed,) conducted a rct in Healthy adults (n=56). Favipiravir vs. Placebo and moxifloxacin 400 mg was evaluated on time-matched, placebo-adjusted change in corrected QT intervals using the Fridericia method (QTcF) from predose (ΔΔQTcF) (max ΔΔQTcF 0.833 msec, 95% CI -1.33-3.00). Favipiravir at single oral doses of 1,200 and 2,400 mg had no detectable effect on the QT/QTc interval in healthy Japanese adults, with maximum placebo-adjusted QTcF changes of 0.833 and 0.500 msec.