Abstract
PurposeThe 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.MethodsThirty-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.ResultsThere were no statistical differences regarding area under the curve (AUC) and maximum concentration (Cmax) between AAFP and OAA. The bioavailability of abiraterone from AAFP versus OAA by geometric mean ratio was AUC0–∞, 95.9% (90% confidence interval [CI] 86.0–106.9); AUC0–t, 99.2% (88.7–110.9); and Cmax, 116.8% (102.2–133.4). The coefficient of variation (CV) was smaller for AAFP versus OAA (AUC0–∞, CV 44.23 vs. 55.61%; AUC0–t, 45.17 vs. 58.16%; Cmax, 54.55 vs. 65.65%, respectively). Both treatments were safe and well tolerated.ConclusionsAAFP plus methylprednisolone provided abiraterone exposure that was comparable to OAA plus prednisone with respect to Cmax 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.
Highlights
Prostate cancer growth is stimulated by androgens
acetate fine particle (AAFP) plus methylprednisolone provided abiraterone exposure that was comparable to originator abiraterone acetate (OAA) plus prednisone with respect to Cmax and area under the curve (AUC)
The following morning (Day 1), subjects were randomly assigned to 1 of 2 treatment regimens: Treatment A consisted of 12 days of methylprednisolone [4 mg twice daily (BID)] with a single dose of AAFP 500 mg on Day 11; Treatment B consisted of 12 days of prednisone (5 mg BID) with a single dose of OAA 1000 mg on Day 11
Summary
All subjects who received at least 1 dose of AAFP or OAA were included in the safety population. Following single-dose administrations of the test and reference drugs on a background of steady-state steroids, the average plasma concentration of abiraterone for AAFP closely overlapped the average plasma concentration for OAA, with the peak level of AAFP being slightly higher (Fig. 1a). Levels of both treatments peaked approximately 2 h postdose. For Cmax, the upper bound of the 90% CI fell slightly above the limit of predefined bioequivalence criteria for AAFP (Table 3)
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