MUNICH, March 27 /PRNewswire/ -- Edoxaban (DU-176b) is a direct Factor Xa inhibitor and is developed to prevent thromboembolic events such as stroke and pulmonary embolism. The Phase II Edoxaban programme has been successfully completed for orthopaedic and cardiological indications.

For the time being it is evident that Edoxaban is currently the only Factor Xa inhibitor with a dose-ranging study conducted with patients with atrial fibrillation and is, thus, starting with optimal dosing in clinical Phase III.

Edoxaban's Phase II results for patients with atrial fibrillation were presented at the American Society of Hematology's 50th annual conference last December in San Francisco. For patients who received 60 mg or 30 mg of Edoxaban once per day, safety and tolerability were shown to be comparable to the vitamin K antagonist Warfarin.

These are the first results worldwide from a clinical study of anticoagulation using an oral Factor Xa inhibitor in patients with atrial fibrillation. The primary goal of this international study was to test the safety of four Edoxaban dosing regimens in comparison to Warfarin. Whilst the frequency of severe and clinically significant non-severe bleedings in the treatment group in which Edoxaban was administered twice a day (60 mg or 30 mg twice daily) was significantly higher in comparison to Warfarin, the frequency in the treatment group receiving one dose a day (Edoxaban 60 mg or 30 mg once daily) was comparable with the incidence in the Warfarin treated patients.

These results are noteworthy and encouraging, since we observed significantly fewer undesired bleeding events in patients who received Edoxaban once a day in comparison to those with a twice daily dose. This indicates that, for this drug, the most convenient dosing schema also seems to be the safer one, said the presenter of the study, Jeffrey I. Weitz, MD, FACP, FRCP, Professor of Medicine and Biochemistry, McMaster University and Director of the Henderson Research Centre, Hamilton (Ontario, Canada).

This dose-ranging study - currently the only one conducted so far using a Factor Xa inhibitor in patients with atrial fibrillation - provided crucial insights with regard to the optimal dosage of Edoxaban for the Phase III study ENGAGE-AF TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation), which has already begun.

In this multi-centre, double-blind and randomised study, approx. 16,500 patients will be assigned to one of three treatment groups: 30 mg Edoxaban once daily, 60 mg Edoxaban once daily and Warfarin. Patients in the Warfarin group will receive Warfarin once a day, with the dosage adjusted so that the coagulation parameters lie within a certain target range (INR values between 2.0 and 3.0). Edoxaban will be compared to Warfarin with regard to the prevention of strokes and systemic embolic events in patients with atrial fibrillation. The frequency of occurrence of severe and clinically significant non-severe bleedings will be used as the primary safety end point.

Approx. 4.5 million people suffer from atrial fibrillation in Europe.

Irregular and rapid beating of the heart's atria can lead to pooling of the blood in places and thus to the formation of blood clots (thromboses). These thromboses can become detached and be carried in the circulation to the brain where they cause strokes by blocking blood vessels. Without anticoagulation treatment, patients with atrial fibrillation have a five times higher risk of having a stroke. The ENGAGE-AF TIMI 48 study is therefore intended to show that these patients can be treated simply, effectively and safely with the Factor Xa inhibitor Edoxaban. The expected median treatment duration in the study is 24 months; the sponsor DAIICHI SANKYO expects the study to conclude in the first half of 2012.

Press contact: Dr. Felix Munzel, Medical/Scientific Affairs CV Europe, Dr. Roland Derwand, New Product Planning CV Europe DAIICHI SANKYO EUROPE GmbH, Telephone +49(0)89-7808-0

Press contact: Dr. Felix Munzel, Medical/Scientific Affairs CV Europe,; Dr. Roland Derwand, New Product Planning CV Europe; DAIICHI SANKYO EUROPE GmbH, Telephone +49(0)89-7808-0