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

Drug Des Devel Ther. 2021 Jul 29:15:3277-3288. doi: 10.2147/DDDT.S323169. eCollection 2021.

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.

Keywords: Chinese healthy volunteers; bioequivalence; pharmacokinetic; phase 1; regorafenib.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Biological Availability
  • Cross-Over Studies
  • Drug Compounding
  • Fasting
  • Female
  • Healthy Volunteers
  • Humans
  • Male
  • Phenylurea Compounds / administration & dosage*
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacokinetics
  • Pyridines / administration & dosage*
  • Pyridines / adverse effects
  • Pyridines / pharmacokinetics
  • Therapeutic Equivalency
  • Young Adult

Substances

  • Phenylurea Compounds
  • Pyridines
  • regorafenib