A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin
Article first published online: 15 MAR 2013
© 2012 Daiichi Sankyo Pharma Development. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society
British Journal of Clinical Pharmacology
Volume 75, Issue 4, pages 966–978, April 2013
How to Cite
Mendell, J., Noveck, R. J. and Shi, M. (2013), A randomized trial of the safety, pharmacokinetics and pharmacodynamics of edoxaban, an oral factor Xa inhibitor, following a switch from warfarin. British Journal of Clinical Pharmacology, 75: 966–978. doi: 10.1111/j.1365-2125.2012.04409.x
- Issue published online: 15 MAR 2013
- Article first published online: 15 MAR 2013
- Accepted manuscript online: 26 AUG 2012 09:42PM EST
- Manuscript Accepted: 23 JUL 2012
- Manuscript Received: 2 DEC 2011
- Daiichi Sankyo
- atrial fibrillation;
To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of edoxaban, an oral direct factor Xa inhibitor, in healthy subjects switching from warfarin.
Seventy-two subjects were randomized to edoxaban 60 mg once daily (n = 48) or matching placebo (n = 24) for 5 days at 24 h after the last dose of warfarin treatment (INR 2.0 to 3.0). Safety/tolerability was the primary outcome measure. Pharmacokinetics, INR, aPTT, anti-FXa, thrombin generation and other coagulation assays were assessed.
Seventy-two subjects were randomized and 64 subjects received at least one dose of edoxaban (n = 43) or placebo (n = 21) after achieving a target INR of 2.0 to 3.0 on warfarin treatment. Edoxaban 60 mg administered 24 h post-warfarin appeared to be safe and well tolerated. Adverse events were similar across treatments. For bleeding-related adverse events, eight subjects tested positive for faecal occult blood, five subjects during warfarin treatment and three subjects during edoxaban treatment. The mean (SD) baseline (post-dose of warfarin) INR was 2.31 (0.193) which increased to 3.84 (0.744) over 2 h during the edoxaban treatment (P < 0.0001 vs. placebo), returning to post-warfarin baseline within 12 h. A similar time course of effects for the other coagulation assays was observed in accordance with the drugs' mechanisms of action.
In this study of healthy subjects, edoxaban administered 24 h after the last dose of warfarin was safe and well tolerated with transient increases across the various coagulation assays above post-warfarin baseline levels.