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

Int J Clin Pharmacol Ther. 2015 Oct;53(10):866-74. doi: 10.5414/CP202388.

Abstract

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amides / adverse effects
  • Amides / blood
  • Amides / pharmacology*
  • Antiviral Agents / adverse effects
  • Antiviral Agents / blood
  • Antiviral Agents / pharmacology*
  • Cross-Over Studies
  • Double-Blind Method
  • Electrocardiography / drug effects*
  • Female
  • Humans
  • Male
  • Pyrazines / adverse effects
  • Pyrazines / blood
  • Pyrazines / pharmacology*
  • Young Adult

Substances

  • Amides
  • Antiviral Agents
  • Pyrazines
  • favipiravir