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

• Published in: Drug design, development and therapy Vol. 16; pp. 3 - 12
• Main Authors: Feng, Zeying, Liu, Yaxin, Kuang, Yun, Yang, Shuang, Li, Jinlei, Ye, Ling, Huang, Jie, Pei, Qi, Huang, Yuanyuan, Yang, Guoping
• Format: Journal Article
• Language: English
• Published: New Zealand Dove Medical Press Limited 01.01.2022; Taylor & Francis Ltd; Dove; Dove Medical Press
• Subjects: abiraterone acetate; Abiraterone Acetate - administration & dosage; Abiraterone Acetate - pharmacokinetics; Acetates; Acetic acid; Administration, Oral; Adverse events; Androgens; Bioavailability; Bioequivalence; Biological Availability; Cancer therapies; Caprylates - administration & dosage; Caprylates - pharmacokinetics; China; Clinical trials; Confidence intervals; Corticosteroids; Cross-Over Studies; Diet; Diet, High-Fat; Drug Compounding; Drug dosages; Excipients; Fasting; Food; food effect; Food safety; High fat diet; Humans; Male; Metastasis; Oral administration; Original Research; Pharmacokinetics; Pharmacology; Plasma; Prednisolone; Prednisone; Prostate cancer; Regression analysis; Safety and security measures; Statistical analysis; Tablets; Therapeutic Equivalency; China; United States > US; pharmacokinetics; abiraterone acetate; food effect; bioequivalence
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S339305

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. 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. The exposure (AUC ) and maximum concentration (C ) 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 C of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The C and AUC 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. 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.