Pharmacokinetics,Safety, and Tolerability of the Direct-acting Hepatitis C Antiviral Sofosbuvir in HealthyChineseSubjects

Purpose

The purpose of this study was to investigate the safety, tolerability, and pharmacokinetic profile of sofosbuvir and its metabolites after a single dose of sofosbuvir 400mg and once daily dosing of sofosbuvir 400mg for 7days in healthy Chinese subjects.

Methods

This Phase I, open-label, single- and multiple-dose study enrolled 14 Chinese subjects aged 18 to 45years with an approximately even distribution of healthy male (n?=?9) and nonpregnant, nonlactating female subjects (n?=?5). Subjects received a single oral dose of sofosbuvir 400mg (one tablet) (morning, fasted conditions; single-dose treatment). After a 3-day washout, subjects received oral sofosbuvir 400mg (one tablet) (morning, fasted) for 7days (multiple dose treatment).

Findings

No significant accumulation of sofosbuvir, GS-566500, or GS-331007 was observed. Steady state of the major metabolite GS-331007 was achieved after 4days of consecutive dosing with sofosbuvir 400mg once daily. Sofosbuvir was generally well tolerated.

Implications

Overall, this study supports the further evaluation of sofosbuvir 400mg in the Chinese population. The pharmacokinetic properties of sofosbuvir, GS-556500, and GS-311007 were found to be broadly similar in healthy Chinese subjects compared with non-Chinese subjects in previous sofosbuvir studies. ChinaDrugTrials.org.cn identifier: CTR20150249.