Edoxaban in Patients Undergoing Total Hip Arthroplasty: A Phase IIb Dose-Finding Study.

Abstract 2098

Poster Board II-75

Introduction: Edoxaban (the free base of DU-176b) is an oral, selective, reversible direct factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders. The aim of this study was to evaluate the efficacy, safety, and dosage regimen of edoxaban in patients undergoing total hip arthroplasty (THA) in Japan and Taiwan. Patients and Methods: This was a randomized, enoxaparin-controlled, multicenter, parallel group study. Double-blind edoxaban 15 mg or 30 mg once daily or open-label, subcutaneous enoxaparin 20 mg BID was administered for 11 to 14 days. Treatment of edoxaban was started within 6 to 24 hours and treatment of enoxaparin was started within 24 to 36 hours after surgery. The primary efficacy endpoint was the incidence of thromboembolic events (composite of asymptomatic deep vein thrombosis [DVT], symptomatic pulmonary embolism [PE], or symptomatic DVT). Bilateral venography was performed at the end of the study and centrally adjudicated. The primary safety endpoint was the incidence of major and clinically relevant non-major bleeding. Prothombin time (PT), PT/international normalized ratio (PT-INR), activated partial thromboplastin time (aPTT) and edoxaban plasma concentration was also assessed. Results: A total of 264 patients were randomized. There were no clinically relevant differences in demographic or baseline characteristics between the treatment groups. The incidence of thromboembolic events was 3.8% (3/78), 2.8% (2/72), and 4.1% (3/74) in 15 mg, 30 mg edoxaban, and enoxaparin groups, respectively. The thromboembolic events were all distal asymptomatic DVT. PT, prothrombin PT-INR, and aPTT were prolonged at 1 to 3 hours post-dose on Day 7 in both edoxaban dose groups. The prolongation observed in the edoxaban dose groups was directly proportional to the plasma edoxaban concentration. No prolongation in PT, PT-INR, or aPTT was observed in the enoxaparin group. The incidence of major and clinically relevant non-major bleeding was 2.2% (2/89) in the 15 mg edoxaban group, 1.2% (1/85) in the 30 mg edoxaban group, and 2.3% (2/87) in the enoxaparin group. There was one major bleeding event in the 30 mg edoxaban group classified as clinically overt bleeding accompanied by a decrease in hemoglobin > 2g/dL. The incidence of adverse drug reactions was 18.0% (16/89) in the 15 mg group, 25.9% (22/85) in the 30 mg of edoxaban group, and 52.9% (46/87) in the enoxaparin group. Conclusions: Oral administration of edoxaban 15 mg and 30 mg showed potential efficacy similar to enoxaparin for the prevention of thromboembolic events in patients undergoing total hip arthroplasty. The incidence of major and clinically relevant non-major bleeding was comparable to that of enoxaparin.