TY - JOUR
T1 - Impact of an alternative steroid on the relative bioavailability and bioequivalence of a novel versus the originator formulation of abiraterone acetate
AU - Olszanski, Anthony J.
N1 - Publisher Copyright:
© 2017, The Author(s).
PY - 2017/9/1
Y1 - 2017/9/1
N2 - 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 (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. Conclusions: AAFP 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.
AB - 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 (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. Conclusions: AAFP 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.
KW - Abiraterone acetate
KW - Bioavailability
KW - Bioequivalence
KW - Methylprednisolone
KW - Prednisone
KW - SoluMatrix Fine Particle Technology™
UR - http://www.scopus.com/inward/record.url?scp=85022227533&partnerID=8YFLogxK
U2 - 10.1007/s00280-017-3360-3
DO - 10.1007/s00280-017-3360-3
M3 - Article
C2 - 28695267
SN - 0344-5704
VL - 80
SP - 479
EP - 486
JO - Cancer Chemotherapy and Pharmacology
JF - Cancer Chemotherapy and Pharmacology
IS - 3
ER -