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

MedStar author(s):
Citation: Cancer Chemotherapy & Pharmacology. 80(3):479-486, 2017 SepPMID: 28695267Institution: MedStar Harbor HospitalDepartment: PAREXEL Early Phase Clinical UnitForm of publication: Journal ArticleMedline article type(s): Journal ArticleSubject headings: *Abiraterone Acetate/tu [Therapeutic Use] | *Prostatic Neoplasms, Castration-Resistant/dt [Drug Therapy] | *Steroids/tu [Therapeutic Use] | Adolescent | Adult | Biological Availability | Humans | Male | Middle Aged | Young AdultYear: 2017Local holdings: Available online from MWHC library: 1997 - presentISSN:
  • 0344-5704
Name of journal: Cancer chemotherapy and pharmacologyAbstract: CONCLUSIONS: AAFP plus methylprednisolone provided abiraterone exposure that was comparable to OAA plus prednisone with respect to C <sub>max</sub> 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.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.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.RESULTS: There were no statistical differences regarding area under the curve (AUC) and maximum concentration (C <sub>max</sub>) between AAFP and OAA. The bioavailability of abiraterone from AAFP versus OAA by geometric mean ratio was AUC<sub>0-</sub>, 95.9% (90% confidence interval [CI] 86.0-106.9); AUC<sub>0-t</sub> , 99.2% (88.7-110.9); and C <sub>max</sub>, 116.8% (102.2-133.4). The coefficient of variation (CV) was smaller for AAFP versus OAA (AUC<sub>0-</sub>, CV 44.23 vs. 55.61%; AUC<sub>0-t</sub> , 45.17 vs. 58.16%; C <sub>max</sub>, 54.55 vs. 65.65%, respectively). Both treatments were safe and well tolerated.All authors: Bosch B, Hussaini A, Nemeth P, Olszanski AJ, Stein CAFiscal year: FY2017Digital Object Identifier: Date added to catalog: 2017-07-18
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 28695267 Available 28695267

Available online from MWHC library: 1997 - present

CONCLUSIONS: AAFP plus methylprednisolone provided abiraterone exposure that was comparable to OAA plus prednisone with respect to C <sub>max</sub> 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.

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.

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.

RESULTS: There were no statistical differences regarding area under the curve (AUC) and maximum concentration (C <sub>max</sub>) between AAFP and OAA. The bioavailability of abiraterone from AAFP versus OAA by geometric mean ratio was AUC<sub>0-</sub>, 95.9% (90% confidence interval [CI] 86.0-106.9); AUC<sub>0-t</sub> , 99.2% (88.7-110.9); and C <sub>max</sub>, 116.8% (102.2-133.4). The coefficient of variation (CV) was smaller for AAFP versus OAA (AUC<sub>0-</sub>, CV 44.23 vs. 55.61%; AUC<sub>0-t</sub> , 45.17 vs. 58.16%; C <sub>max</sub>, 54.55 vs. 65.65%, respectively). Both treatments were safe and well tolerated.

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