Pharmacokinetics and Bioequivalence of Abiraterone Acetate Tablets in Healthy Chinese Volunteers: An Open, Randomized, Single-Dose, Three-Period, Three-Sequence Crossover Study

Abstract

Background and Objective: Abiraterone acetate tablet is an inhibitor of androgen synthesis, primarily for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioequivalence and pharmacokinetics of the reference and test formulations of abiraterone acetate tablets in healthy Chinese volunteers. Methods: A single-center, open, single-dose, randomized, three-period, three-sequence, semi-repeat (only repeated reference formulations), and reference formulation-corrected fasting reference-scaled average bioequivalence test was conducted in 36 healthy volunteers included in this study. Volunteers were randomly assigned to one of three groups in a 1:1:1 ratio. There was a minimum 7-day washout period between each dose. Blood samples were collected at prescribed time intervals, the plasma concentration of abiraterone acetate tablets was determined by liquid chromatography-tandem mass spectrometry, and adverse events were recorded. Results: Under fasting conditions, the maximum plasma concentration (C max) was 27.02 ± 14.21 ng/mL, area under the concentration-time curve from time zero to time t (AUCt) was 125.30 ± 82.41 h·ng/mL, and AUC from time zero to infinity (AUC∞) was 133.70 ± 83.99 h·ng/mL. The 90% confidence intervals (CIs) of the geometric mean ratio (GMR) of AUCt and AUC∞ were in the range of 0.8000–1.2500, and the coefficient of variation (CVWR) of C max was more than 30%. The Critbound result was − 0.0522, and the GMR was between 0.8000 and 1.2500. Conclusion: Both test and reference formulations of abiraterone acetate tablets were bioequivalent in healthy Chinese subjects under fasting conditions. Trial registration: ClinicalTrials.gov identifier NCT04863105, registered 26 April 2021—retrospectively registered (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000ARAA&selectaction=Edit&uid=U00050YQ&ts=2&cx=-vbtjri