Abstract A194: A QT/QTc and multi-dose pharmacokinetic (PK) study of abiraterone acetate (AA) plus prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC).

Background: AA is the prodrug of abiraterone (A), an androgen biosynthesis inhibitor that selectively inhibits CYP17, thereby blocking testicular, adrenal, and prostatic intratumoral androgen biosynthesis. In a phase 3 study, AA+P demonstrated survival improvements in post-docetaxel mCRPC pts (De Bono ESMO 2010). ADT with an LHRH analog (LHRHa) has been associated with median QTc interval prolongation of 9–21 msec (Garnick ASCO 2004). Primary objective: effects of AA+P on QT/QTc interval duration in mCRPC pts receiving LHRHa. Secondary objectives: pharmacokinetics (PK) of AA and abiraterone (A) after single/multiple doses of AA. Methods: In this open-label, single-arm phase 1b study (COU-AA-006/NCT00910754), 33 mCRPC pts with disease progression after failure of GnRH hormone therapy, a PSA ≥2 ng/mL and ≤1 course of prior chemotherapy, received AA 1000mg orally QD + P 5mg orally BID. ECGs were collected in triplicate using 12-lead Holter monitoring. Baseline ECGs were obtained on Cycle (C)1 Day (D)-1. Serial ECG recordings and time-matched PK blood samples were collected over 24 hrs on C1D1 and C2D1. Serial PK blood samples were also collected over 24 hrs on C1D8. Results: After AA administration, the upper bound of the 2-sided 90% CI for the mean baseline-adjusted QTcF change was Conclusions: There is no significant effect of AA+P on the cardiac QT/QTc interval in mCRPC pts. No relationship between change in QTcF and A plasma concentration was observed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr A194.