Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer : An Open-label Phase 1 Study

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Massard , C , Penttinen , H M , Vjaters , E , Bono , P , Lietuvietis , V , Tammela , T L , Vuorela , A , Nykanen , P , Pohjanjousi , P , Snapir , A & Fizazi , K 2016 , ' Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer : An Open-label Phase 1 Study ' , European Urology , vol. 69 , no. 5 , pp. 834-840 . https://doi.org/10.1016/j.eururo.2015.09.046

Title: Pharmacokinetics, Antitumor Activity, and Safety of ODM-201 in Patients with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer : An Open-label Phase 1 Study
Author: Massard, Christophe; Penttinen, Heidi M.; Vjaters, Egils; Bono, Petri; Lietuvietis, Vilnis; Tammela, Teuvo L.; Vuorela, Annamari; Nykanen, Pirjo; Pohjanjousi, Pasi; Snapir, Amir; Fizazi, Karim
Contributor: University of Helsinki, Department of Oncology
University of Helsinki, Clinicum
Date: 2016-05
Language: eng
Number of pages: 7
Belongs to series: European Urology
ISSN: 0302-2838
URI: http://hdl.handle.net/10138/162242
Abstract: Background: ODM-201 is a novel second-generation androgen receptor inhibitor for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Objective: To evaluate the pharmacokinetics of ODM-201 tablet products and preliminary long-term safety, tolerability, and antitumor activity of ODM-201 in chemotherapy-naive men with mCRPC. Design, setting, and participants: Thirty patients were enrolled in this open-label phase 1 trial. Patients received a single 600-mg dose of ODM-201 in capsules with food and one 600-mg dose of ODM-201 tablet product (TabA or TabB) with food and in the fasted state in a random order. In the extension, patients received 600 mg twice daily ODM-201 taken with food in capsules. Outcome measurements and statistical analysis: We analyzed the pharmacokinetics of ODM-201 tablet formulations. Safety and tolerability were assessed until disease progression or an intolerable adverse event (AE). Antitumor activity was assessed by prostate-specific antigen (PSA) levels and imaging. Results and limitations: The capsule: TabA ratio of area under the concentration-time curve from time zero to the last sample at 48 h was 1.06 (90% confidence interval [CI], 0.91-1.24); the capsule: TabB ratio was 0.97 (90% CI, 0.82-1.14). At week 12, 25 of 30 patients (83%) had a PSA response (>= 50% reduction from baseline). Median time to radiographic progression was 66 wk (95% CI, 41-79). Most common AEs were fatigue (n = 4 [13%]) and nausea (n = 4 [13%]). Conclusions: The study showed that the tablet formulation of ODM-201 had similar pharmacokinetics compared with the capsule. Treatment with a 600-mg twice daily dose of ODM-201 provided anticancer activity and was well tolerated in men with chemotherapy-naive mCRPC. Patient summary: The findings of this study showed that ODM-201 is well tolerated and provided antitumor activity in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (mCRPC) and that the 300-mg tablet formulation can be used in further clinical studies. A phase 3 trial with ODM-201 600 mg twice daily in patients with non-mCRPC is ongoing. (C) 2015 European Association of Urology. Published by Elsevier B.V.
Subject: Androgen receptor inhibitor
Castration-resistant prostate cancer
ODM-201
ENZALUTAMIDE
ANTIANDROGEN
SURVIVAL
ARN-509
3126 Surgery, anesthesiology, intensive care, radiology
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