Single-dose, four-way crossover, open-label, relative bioavailability (BA) studies of a novel formulation of abiraterone acetate (AA) versus the reference formulation under fasted conditions in healthy male subjects.

Abstract

e605 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic variability in abiraterone exposure in healthy subjects. AA fine particle (AAFP) is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology) that was designed to provide improved BA versus the OAA formulation. Methods: In Study 1, 20 subjects were randomized in a crossover design to single doses of AAFP 100, 200, or 400 mg or OAA 1000 mg. To further expand the AAFP dose range, 36 subjects were randomized in a crossover design to AAFP 125, 500, or 625 mg or OAA 1000 mg in Study 2. Both studies included a 7-day washout period prior to crossover. Results: AAFP 500 mg BA relative to OAA 1000 mg measured by the ratio of test-to-reference geometric means was AUC0-t 93.4% (90% CI: 85.3–102.4%), AUC0-∞ 91.0% (90% CI: 83.3–99.4%), and Cmax99.8% (90% CI: 86.3–115.5%). Dose proportionality was seen across all AAFP dose levels (see table). Between-subject variability for AAFP 500 and 625 mg was similar to OAA 1000 mg. No significant AAFP-related adverse events (AEs), serious AEs, or deaths occurred. Treatment-emergent AEs were mostly Grade 1. Conclusions: AAFP demonstrated improved BA and AAFP 500 mg was bioequivalent to OAA 1000 mg in healthy male volunteers under single dose and fasted conditions. AAFP showed dose proportionality across all doses studied (100–625 mg). Clinical trial information: NCT02737332. [Table: see text]