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

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 noncompartmental 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 ratio T/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.

Automated summary

The study demonstrated that two formulations of 40 mg Regorafenib were bioequivalent under fasting and fed conditions in healthy Chinese volunteers, with similar and generally good safety profiles.