To evaluate the bioequivalence and safety of a generic (or test) sofosbuvir 400-mg tablet versus a brand-named (or reference) sofosbuvir (Sovaldi®) 400-mg tablet in healthy Chinese volunteers under the fasting and fed conditions.
In this single-dose, randomized, open-label, two-sequence, four-period, crossover study, 52 healthy adult Chinese volunteers were enrolled for the fasting (n = 26) and fed (n = 26) conditions. Under each condition, subjects were randomized to receive initial treatment according to either the test-reference-test-reference or the reference-test-reference-test sequence, and then the treatment was switched to the other sequence after a 7-day washout period. Plasma concentrations of sofosbuvir were measured by high-performance liquid chromatography-tandem mass spectrometry. Non-compartmental pharmacokinetic (PK) analysis was performed using Phoenix WinNonlin software to derive PK parameters for sofosbuvir. Adverse events (AEs) were monitored during the study.
All 52 subjects completed the study. The observed PK parameters, including t1/2, Tmax, Cmax, AUC0–t, and AUC0–∞, were similar between the generic and brand-named sofosbuvir products under fasting and fed conditions. The 90% confidence intervals of test/reference ratios for Cmax, AUC0–t and AUC0–∞ were within the bioequivalence acceptance range. One subject experienced an AE while taking the reference product under the fasting condition, whereas six experienced nine AEs (six and three, respectively, while taking the generic and reference products). All AEs were mild.
The generic sofosbuvir is bioequivalent to the brand-named sofosbuvir under both fasting and fed conditions, and the generic sofosbuvir is as safe and well tolerated as the brand-named product in healthy Chinese volunteers.
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