title: Lack of effect of favipiravir, a novel antiviral agent, on QT interval in healthy Japanese adults.
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.
  
  
  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.
authors: Yuji
authors: Y
authors: Kumagai
authors: Yuji
authors: Y
authors: Murakawa
authors: Tomoko
authors: T
authors: Hasunuma
authors: Masako
authors: M
authors: Aso
authors: Wakako
authors: W
authors: Yuji
authors: Tsutomu
authors: T
authors: Sakurai
authors: Masahiko
authors: M
authors: Noto
authors: Tetsuya
authors: T
authors: Oe
authors: Akiko
authors: A
authors: Kaneko
mesh_terms: D000328:Adult; D000577:Amides / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D000998:Antiviral Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004562:Electrocardiography / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D011719:Pyrazines / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; C462182:favipiravir