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
التفاصيل البيبلوغرافية
العنوان:
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
Qian Zhang,1,2 Zhiqiang Wang,1â 3 Jingying Wu,1,2 Zhen Zhou,3 Renpeng Zhou,1,2 Wei Hu1,2 1Department of Clinical Pharmacology, The Second Hospital of Anhui Medical University, Hefei, Peopleâs Republic of China; 2Anhui Provincial Institute of Translational Medicine, Hefei, Peopleâs Republic of China; 3Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, AustraliaCorrespondence: Renpeng Zhou; Wei Hu Email zhourenpeng@ahmu.edu.cn; huwei@ahmu.edu.cnBackground: 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 80â 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
