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 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.

Keywords:

• regorafenib
• phase 1
• pharmacokinetic
• bioequivalence
• Chinese healthy volunteers

Acknowledgments

We thank the participants for involving in this trial. This study was funded by Yangtze River Pharmaceutical Group Co., Ltd.; National Major Scientific and Technological Special Project (2020ZX09201014).

Data Sharing Statement

The data that support the findings of this study are available from the corresponding authors upon reasonable request for legitimate research purpose.

Disclosure

The authors declare no conflicts of interest for this work.