Impact of an alternative steroid on the relative bioavailability and bioequivalence of a novel versus the originator formulation of abiraterone acetate

Abstract

Purpose

The originator abiraterone acetate (OAA) formulation is used for the treatment of metastatic castration-resistant prostate cancer (mCRPC). This study evaluated the bioavailability and bioequivalence of a novel formulation, abiraterone acetate fine particle (AAFP), versus OAA on a steady-state background of steroids.

Methods

Thirty-seven healthy male subjects were randomized in a crossover design to receive methylprednisolone (4 mg twice daily) or prednisone (5 mg twice daily) for 12 days in Period 1. On Day 11 of Period 1, subjects given methylprednisolone received a single dose of AAFP 500 mg, and subjects given prednisone received a single dose of OAA 1000 mg under fasted conditions. After a 2-week steroid washout period, subjects received the alternate treatments in Period 2.

Results

There were no statistical differences regarding area under the curve (AUC) and maximum concentration (C _max) between AAFP and OAA. The bioavailability of abiraterone from AAFP versus OAA by geometric mean ratio was AUC_0–∞, 95.9% (90% confidence interval [CI] 86.0–106.9); AUC_0–t , 99.2% (88.7–110.9); and C _max, 116.8% (102.2–133.4). The coefficient of variation (CV) was smaller for AAFP versus OAA (AUC_0–∞, CV 44.23 vs. 55.61%; AUC_0–t , 45.17 vs. 58.16%; C _max, 54.55 vs. 65.65%, respectively). Both treatments were safe and well tolerated.

Conclusions

AAFP plus methylprednisolone provided abiraterone exposure that was comparable to OAA plus prednisone with respect to C _max and AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced pharmacokinetic variability may positively influence clinical outcomes and warrants further study in mCRPC patients.

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