Relative bioavailability (BA) and bioequivalence (BE) study of abiraterone acetate (AA) fine particle (AAFP) with methylprednisolone (MP) and a reference formulation with prednisone (PN) in healthy male subjects.

Abstract

e16538 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer when taken in combination with PN. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic (PK) variability. AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology™) that was designed to provide improved BA. In a prior study in healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg when given in the fasted state. In this study, AAFP was evaluated in subjects in a fasted state with steady state (SS) MP, an alternative steroid to PN. Methods: Subjects aged 18–50 years were randomized in a crossover design to receive MP (4 mg BID) or PN (5 mg BID) for 12 days in Period 1. On Day 11 of Period 1, subjects given MP received a single dose of AAFP 500 mg (test) and subjects given PN received a single dose of OAA 1000 mg (reference). After a 2-week steroid washout period, subjects received the alternate treatments in Period 2. Results: There were no statistical differences with regard to abiraterone AUC ( P≥0.38) and Cmax ( P= 0.22) between AAFP 500 mg and OAA 1000 mg (Table). Geometric mean ratio (GMR), a measure of BE, was 95.9% (90% CI: 86.0–106.9%) for AUC0-∞, 99.2% (90% CI: 88.7–110.9%) for AUC0-t, and 116.8% (90% CI: 102.2–133.4%) for Cmax. GMR of AUC0-∞ and AUC0-t, fell within the 80–125% range for BE, and Cmax 90% CI was just outside the upper limit. The coefficient of variance (CV) for both AUC and Cmaxwas smaller for AAFP compared with OAA. Both treatments were safe and well tolerated. Conclusions: AAFP 500 mg with MP gave comparable exposure to OAA 1000 mg with PN with respect to Cmaxand AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced PK variability could improve clinical outcomes and warrants further study. [Table: see text]