scholarly journals A prospective phase I multicentre randomized cross-over pharmacokinetic study to determine the effect of food on abiraterone pharmacokinetics

2019 ◽  
Vol 84 (6) ◽  
pp. 1179-1185 ◽  
Author(s):  
Floor J. E. Lubberman ◽  
Guillemette E. Benoist ◽  
Winald Gerritsen ◽  
David M. Burger ◽  
Niven Mehra ◽  
...  
Keyword(s):  
Phase I ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Prospective Phase ◽  
Effect Of Food ◽  
Multi Center Study ◽  
Toxicity Relationship

Abstract Purpose Abiraterone acetate is used at a fixed oral dose of 1000 mg once daily (OD) taken fasted. By administering abiraterone acetate with food, a reduced dose can potentially be given while maintaining equivalent abiraterone exposure. Moreover, administering abiraterone acetate with a breakfast is considered more patient friendly. The aim of this study was to establish the bio-equivalent lower dose of abiraterone when taken with a continental breakfast (CB) compared to the standard intake of 1000 mg OD fasted. Methods In this phase I, randomized cross-over, multi-center study, abiraterone pharmacokinetics (PK) were evaluated in patients with metastatic castration-resistant prostate cancer who were treated for 14 days with 1000 mg abiraterone acetate taken fasted, followed by 14 days of treatment with 500 mg taken with a CB. Results 14 patients were enrolled into the study, of whom 12 were eligible for PK analysis. The geometric mean ratio (GMR) (fed/fasted) was 0.88 (90% CI 0.73–1.07) for area-under-the-curve (AUC0–24h), 1.03 (90% CI 0.79–1.34) for Cmax and 0.81 (90% CI 0.60–1.10) for Ctrough, respectively. High inter-patient variability (> 50%) was found for all PK parameters under both intake conditions. Patients seemed to be slightly more satisfied about the intake of 500 mg abiraterone acetate when taken with a CB compared to 1000 mg fasted. Conclusion In conclusion, a bioequivalent lower dose of abiraterone taken with food could not be established in our study. Although based on the absence of a exposure–toxicity relationship, the strict bioequivalence margins as defined by the FDA guidelines could be applied more flexible for abiraterone. Information on the effect of food on abiraterone pharmacokinetics as presented in our study can be used for patients with difficulties taken their medication fasted.

Results of a multicenter phase I/II trial of abiraterone acetate plus BEZ235 in metastatic, castration-resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e16042-e16042 ◽  
Author(s):  
Adam Phillip Siegel ◽  
Alan Haruo Bryce ◽  
Amy M. Lin ◽  
Terence W. Friedlander ◽  
Andrew Caleb Hsieh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Multicenter Phase

Dose-modified abiraterone acetate (AA) in men with metastatic castration-resistant prostate cancer (mCRPC): The Princess Margaret Cancer Centre (PM) experience.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 61-61 ◽  
Author(s):  
Raya Leibowitz-Amit ◽  
Eshetu G. Atenafu ◽  
Jo-An Seah ◽  
Arnoud J. Templeton ◽  
Francisco Emilio Vera-Badillo ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Low Dose ◽  
Abiraterone Acetate ◽  
Low Doses ◽  
Fasting State ◽  
Castration Resistant Prostate Cancer ◽  
High Fat ◽  
Castration Resistant ◽  
Psa Response

61 Background: AA prolongs survival in mCRPC and is used pre- and post-chemotherapy. In the phase I trial, AA showed anti-tumor activity at 250 or 500 mg daily (‘low doses’). In addition, pharmacokinetic analysis showed that when AA was administered with a high-fat meal vs the fasting state, drug exposure was increased by 4.4-fold [ Attard G et al. Phase I clinical trial of a selective inhibitor of CYP17, abiraterone acetate, confirms that castration-resistant prostate cancer commonly remains hormone driven. J Clin Oncol 2008; 26: 4563-4571.]. Based on this, at our cancer centre low-dose AA is sometimes prescribed with high-fat meals to men who otherwise cannot access the drug due to funding constraints, particularly in the pre-chemotherapy setting. Our aim was to study the association between AA dose, PSA response and progression-free survival (PFS). Methods: All men receiving AA at PM (Nov2009-Mar2013) were reviewed retrospectively. PSA response rate (PSA-RR) was defined according to PCWG2 criteria as a confirmed decrease ≥50% in PSA. PFS was defined from start of AA to PSA progression, clinical progression, drug cessation or death. Associations between dose, PSA-RR and PFS were assessed using chi-square and logrank tests, respectively, for all patients and for the sub-group of chemo-naive patients. Results: 109 men were treated with AA, 89 at a full dose of 1000 mg in the fasting state, 20 at low doses with high-fat meals. There was no significant difference in PFS between the two dose levels for all men. PSA-RR was non-significantly lower in chemo-naive men treated with low doses compared to full dose (p=0.09; table). Conclusions: Administration of low dose AA with high-fat meals is not associated with shorter PFS despite a trend to lower PSA-RR. These results are clinically relevant in resource-limited settings and warrant further prospective clinical research. [Table: see text]

Relative bioavailability (BA) and bioequivalence (BE) study of abiraterone acetate (AA) fine particle (AAFP) with methylprednisolone (MP) and a reference formulation with prednisone (PN) in healthy male subjects.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16538-e16538
Author(s):  
Azra Hussaini ◽  
Anthony J. Olszanski ◽  
Cy Aaron Stein ◽  
Bill Bosch ◽  
Paul Nemeth
Keyword(s):  
Single Dose ◽  
Fine Particle ◽  
Drug Exposure ◽  
Geometric Mean ◽  
Relative Bioavailability ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Fasted State ◽  
Period 2

e16538 Background: AA is approved for treatment of metastatic castration-resistant prostate cancer when taken in combination with PN. The originator AA (OAA) formulation is poorly absorbed and exhibits large pharmacokinetic (PK) variability. AAFP is a proprietary formulation (utilizing SoluMatrix Fine-Particle Technology™) that was designed to provide improved BA. In a prior study in healthy subjects, AAFP 500 mg was established as bioequivalent to OAA 1000 mg when given in the fasted state. In this study, AAFP was evaluated in subjects in a fasted state with steady state (SS) MP, an alternative steroid to PN. Methods: Subjects aged 18–50 years were randomized in a crossover design to receive MP (4 mg BID) or PN (5 mg BID) for 12 days in Period 1. On Day 11 of Period 1, subjects given MP received a single dose of AAFP 500 mg (test) and subjects given PN received a single dose of OAA 1000 mg (reference). After a 2-week steroid washout period, subjects received the alternate treatments in Period 2. Results: There were no statistical differences with regard to abiraterone AUC ( P≥0.38) and Cmax ( P= 0.22) between AAFP 500 mg and OAA 1000 mg (Table). Geometric mean ratio (GMR), a measure of BE, was 95.9% (90% CI: 86.0–106.9%) for AUC0-∞, 99.2% (90% CI: 88.7–110.9%) for AUC0-t, and 116.8% (90% CI: 102.2–133.4%) for Cmax. GMR of AUC0-∞ and AUC0-t, fell within the 80–125% range for BE, and Cmax 90% CI was just outside the upper limit. The coefficient of variance (CV) for both AUC and Cmaxwas smaller for AAFP compared with OAA. Both treatments were safe and well tolerated. Conclusions: AAFP 500 mg with MP gave comparable exposure to OAA 1000 mg with PN with respect to Cmaxand AUC. Less drug exposure variability was observed with AAFP compared with OAA. Reduced PK variability could improve clinical outcomes and warrants further study. [Table: see text]

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