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

Purpose

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 (AUC _0-∞) and maximum concentration (C _max) 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 _max of orally administered abiraterone as R-AbA in a modified fed state was 5.9 times and AUC _0-∞ was 4.3 times, respectively, higher than those in of orally administered abiraterone as N-AbA in a high-fat diet. The C _max and AUC _0-∞ 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.