Bioequivalence and pharmacokinetic evaluation of two oral formulations of regorafenib: An open-label, randomised, single-dose, two-period, two-way crossover clinical trial in healthy chinese volunteers under fasting and fed conditions

Abstract

Background: Regorafenib is an oral multi-kinase inhibitor approved for the treatment of solid tumours, but the pharmacokinetic profile of regorafenib in the Chinese population is unclear. Objective: The aim of this study was to examine the pharmacokinetics, bioequivalence, and safety of two formulations of regorafenib 40 mg in healthy Chinese volunteers under fed and fasting conditions. Methods: A single-centre, randomised, open-label, two-period, two-way crossover phase 1 trial was conducted by randomising a single oral dose of test (T) or reference (R, Stivarga® ) regorafenib (40 mg) to healthy Chinese volunteers under both fasting and fed conditions (high-fat and high-calorie diet). Pharmacokinetic parameters were calculated using non-compartmental methods. Adverse events were recorded to assess drug safety. Results: Sixty-six participants were enrolled for both fasting and fed treatments. The 90% CIs geometric least-square means of ratioT/R for regorafenib were completely contained within the equivalence margin of 80–125% under both fasting and fed conditions. Both formulations displayed similar and generally good safety profiles. Conclusion: Single oral dose of the T (40 mg) and R (40 mg) regorafenib was bioequivalent under fasting and fed conditions and had similar favourable safety profiles among healthy Chinese volunteers.