Abstract

Objective: A thorough QT study of favipiravir, a novel antiviral agent, was conducted using a randomized, doubleblind, 4-group, 4-period crossover, placeboand 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.

Author Details

Authors

• Yuji Kumagai¹
• Yuji Murakawa²
• Tomoko Hasunuma³
• Masako Aso¹
• Wakako Yuji⁴
• Tsutomu Sakurai⁵
• Masahiko Noto⁵
• Tetsuya Oe⁵
• Akiko Kaneko⁶

Departments

• ¹ Clinical Trial Center, Kitasato University Hospital, Kanagawa,
• ² Fourth Department of Internal Medicine, Mizonokuchi Hospital, Teikyo University School of Medicine, Kanagawa,
• ³ Clinical Pharmacology Center, Oita University Hospital, Oita,
• ⁴ Biomedical Research Center, Kitasato Institute Hospital, Tokyo,
• ⁵ Clinical Research Department, Toyama Chemical Co., Ltd., Tokyo, and
• ⁶ Data Science and Administration Department, Toyama Chemical Co., Ltd., Tokyo, Japan

Address

Yuji Kumagai, MD, PhD
Clinical Trial Center, Kitasato University Hospital
15-1 Kitazato 1-chome, Minami-ku,
Sagamihara, Kanagawa, 252-0375 Japan
Email: [email protected]

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