Absorption of a novel formulation of abiraterone acetate (AA) fine particle (AAFP) under fed and fasted conditions.

Abstract

e606 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer (mCRPC). In healthy subjects administered the originator AA (OAA) formulation, AUC and Cmaxincreased by 10- and 17-fold, respectively, when administered after a high-fat meal relative to the fasted state.1 AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology) of AA designed to improve the oral bioavailability (BA) of AA, and to potentially reduce food effects compared with the OAA formulation. In healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg in a prior study when taken in fasted conditions. Methods: Healthy male subjects (N = 25) fasted 10-h overnight before randomization in a crossover design to a single 500 mg dose of AAFP under fasted or fed (high-fat FDA breakfast 30 min before AAFP administration) conditions. There was a 7-day washout period prior to crossover; 22 subjects completed the study. Results: Drug exposure of AAFP 500 mg was significantly ( P< 0.0001) greater under fed vs fasted conditions (Table). Following a single dose of AAFP 500 mg, relative BA measured by the ratio of test-to-reference geometric means of AUC and Cmax of abiraterone indicated that drug exposure increased under fed conditions by approximately 4.5- and 6.5-fold, respectively, vs under fasted conditions. AAFP 500 mg was safe and well-tolerated under fed or fasted conditions. Conclusions: AAFP 500 mg under fed conditions has higher BA than under fasted conditions. A direct comparative study between AAFP 500 mg and OAA 1000 mg under restricted food conditions is underway in patients with mCRPC. 1US FDA. CDER. Abiraterone Acetate NDA 202379 Review, 2010. Clinical trial information: NCT02737332. [Table: see text]