Open-Label, Phase I, Pharmacokinetic Studies in Healthy Chinese Subjects to Evaluate the Bioequivalence and Food Effect of a Novel Formulation of Abiraterone Acetate Tablets

Abstract

Zeying Feng,1,2,* Yaxin Liu,1,2,* Yun Kuang,2 Shuang Yang,2 Jinlei Li,2 Ling Ye,2 Jie Huang,2 Qi Pei,3 Yuanyuan Huang,1,4 Guoping Yang1– 3 1XiangYa School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 2Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 3Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Clinical Research and Develpment Division II, Jiangsu Hengrui Medicine Co., Ltd., Shanghai, 201200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuanyuan HuangClinical Research and Develpment Division II, Jiangsu Hengrui Medicine Co., Ltd., 1288 Haike Road, Pudong District, Shanghai, 201200, People’s Republic of ChinaEmail [email protected] YangThe Third Xiangya Hospital, Central South University, Yinpenling Street, Yuelu District, Changsha, Hunan, 410013, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Abiraterone acetate tablets (I)(N-AbA) is a novel tablet co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). This study aimed to compare the pharmacokinetics, bioequivalence, safety, and food effects of N-AbA with the reference ZYTIGA® (R-AbA) in healthy Chinese male subjects.Patients and Methods: This study was conducted in three parts. Part I was an open, dose-escalation trial conducted in 16 Chinese healthy males; Part II was a randomized, open-label, 2 × 4 crossover, single-dose bioequivalence trial conducted in 36 subjects; Part III was a randomized, 3 × 3 crossover trial conducted on 24 volunteers to investigate the effect of food on the pharmacokinetics of N-AbA.Results: The exposure (AUC0-∞) and maximum concentration (Cmax) of abiraterone and excipient SNAC were linear in the range of 75– 450 mg dose. The bioavailability of N-AbA 300 mg was equivalent to that of R-AbA 1000 mg. The drug exposure of prednisone and prednisolone was not affected by SNAC co-administration. The Cmax of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC0-∞ was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The Cmax and AUC0-∞ of orally administered abiraterone as N-AbA on a high-fat diet were 2.2 times and 2 times, respectively, higher than those on a fasting state. All adverse events reported in the three parts of the study were grade 1 or 2, and no serious adverse events were reported.Conclusion: These three Phase I trials showed that N-AbA and excipient SNAC had excellent linear pharmacokinetic characteristics. A single dose of N-AbA 300 mg was bioequivalent to R-AbA 1000 mg in healthy subjects under fasting conditions. Meanwhile, SNAC had no effect on the pharmacokinetics of prednisone and prednisolone. The effect of food on N-AbA was significantly lower than that on R-AbA.Keywords: food effect, pharmacokinetics, abiraterone acetate, bioequivalence

Keywords

• food effect
• pharmacokinetics
• abiraterone acetate
• bioequivalence