Daiichi Sankyo announced on 1 December 2010 that it has successfully completed patient enrolment for its phase III ENGAGE AF-TIMI 48 clinical study of edoxaban, a direct, specific, oral factor Xa inhibitor that is being investigated in two different dosing regimens given once-daily, to prevent the occurrence of strokes and systemic embolic events in patients with atrial fibrillation (AF).
The ENGAGE AF-TIMI 48 study began enrolment in November 2008. It is an event-driven, randomised, double-blind, double-dummy, parallel group, multicentre, multi-national study designed to assess the efficacy and safety of edoxaban compared to the current standard of care, warfarin. Patients in the study are randomised to one of three treatment groups: 30mg edoxaban once-daily, 60mg edoxaban once-daily, or warfarin. In addition, edoxaban doses are further adjusted to treat patients with renal impairment and/or low body weight, or those taking strong P-glycoprotein inhibitors. Those randomised to warfarin are dosed once-daily to achieve an International Normalised Ratio (INR) between 2.0 and 3.0.
“The completion of enrolment for the largest AF outcomes study ever undertaken – ENGAGE AF-TIMI 48 – marks a key milestone in the development of edoxaban and for Daiichi Sankyo,” said Glenn Gormley, chief science officer and president, Daiichi Sankyo Pharma Development.
ENGAGE AF-TIMI 48 (Effective anticoagulation with factor Xa next generation in atrial fibrillation), enrolled 21,107 subjects at nearly 1,400 clinical trial sites located throughout North America, South America, Africa, Asia, Europe and Australia/New Zealand. The primary endpoint of this study is to compare the efficacy of edoxaban to warfarin in the prevention of stroke and systemic embolic events. The primary safety assessment is the incidence of major bleeding events.
“As new options to prevent stroke in AF patients become available, it will be important that these treatments eliminate the need for extensive monitoring and dietary modifications,” said Elliott Antman, professor of Medicine, Harvard Medical School, senior investigator with the Brigham and Women’s Hospital-based TIMI Study Group. “Based on phase II study results, edoxaban has shown promise of potentially addressing the needs of patients with AF and the physicians caring for them.”