The Effect of Food on the Absorption of Abiraterone Acetate from a Fine Particle Dosage Form: A Randomized Crossover Trial in Healthy Volunteers

Abstract

Abiraterone acetate (AA) is approved for treatment of metastatic castration-resistant prostate cancer. The originator AA (OAA) formulation has been associated with AUC and C max increases of 10- and 17-fold, respectively, when administered following a high-fat meal relative to the fasted state. AA fine particle (AAFP) is a proprietary formulation (utilizing SoluMatrix Fine Particle Technology™) that has enhanced dissolution properties. It was designed to increase the oral bioavailability of AA, and to potentially reduce variability in drug exposure and food effects compared with OAA. In healthy subjects, AAFP 500 mg was previously shown to be bioequivalent to OAA 1000 mg when taken in fasted conditions. Healthy male subjects (N = 25) fasted 10 h overnight before randomization in a crossover design received a single 500-mg dose of AAFP under fasted or fed conditions. The extent of AAFP drug exposure was significantly (P < 0.001) greater under fed versus fasted conditions. Following a single dose of AAFP, relative bioavailability measured by the geometric mean ratio of AUC and C max of abiraterone indicated that the extent of drug absorption increased under fed conditions by approximately 4.5- and 6.5-fold, respectively, versus under fasted conditions. AAFP was safe and well-tolerated. AAFP under fed conditions has higher bioavailability and is not bioequivalent to AAFP under fasted conditions. The food effect with AAFP 500 mg was approximately 50% less than what has been reported for OAA 1000 mg. Although diminished, the potential for excessive abiraterone plasma concentrations in patients who are noncompliant with dosing instructions remains. Churchill Pharmaceuticals LLC.