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Direct Factor Xa Inhibitor (direct + factor_xa_inhibitor)
Selected AbstractsRivaroxaban , an oral, direct Factor Xa inhibitor , lessons from a broad clinical study programmeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2009Sylvia Haas Abstract Anticoagulants are recommended for the prevention and treatment of venous thromboembolism (VTE), prevention of stroke in patients with atrial fibrillation (AF) and secondary prevention in patients with acute coronary syndrome (ACS). There is a clinical need for novel anticoagulants offering improvements over current standard of care, such as fixed oral dosing and no need for routine monitoring. Rivaroxaban, an oral, once-daily, direct Factor Xa inhibitor, has recently completed the RECORD phase III programme for the prevention of VTE in patients undergoing total hip or knee replacement (THR or TKR), an indication for which it is approved in Europe and Canada. It is being investigated in large-scale phase III studies for VTE treatment and prevention of stroke in patients with AF, and phase III studies will soon commence for secondary prevention in patients with ACS. Phase I studies demonstrated that no routine anticoagulation monitoring was required, while phase II studies suggested that fixed daily doses had a wide therapeutic window. The four RECORD studies consistently showed that rivaroxaban was significantly more effective than enoxaparin in the prevention of VTE after THR and TKR, with a similar safety profile. This review describes the development of this novel anticoagulant, from bench to bedside. [source] Syntheses of [14C]BAY 59-7939 and its radiolabeled metabolite M-4JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 11 2006U. Pleiss Abstract BAY 59-7939 is a novel, oral, direct Factor Xa inhibitor in clinical development for the prevention and treatment of thromboembolic diseases. Radiolabeled BAY 59-7939 was required for drug absorption, distribution, metabolism and excretion (ADME studies). The BAY 59-7939 was labeled with carbon-14 in the carboxamide group in one step in an overall radiochemical yield of 85% starting from 4-{4-[(5S)-5-(aminomethyl)-2-oxo-1,3-oxazolidin-3-yl]phenyl}mor-pholin-3-one and 5-chlorothiophene-2-[14C]carboxylic acid. The radiolabeled metabolite M-4 was prepared in 77% yield starting from [1- 14C]glycine and 5-chlorothiophene-5-carboxylic acid. Copyright © 2006 John Wiley & Sons, Ltd. [source] A dose escalation study of YM150, an oral direct factor Xa inhibitor, in the prevention of venous thromboembolism in elective primary hip replacement surgeryJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2007B. I. ERIKSSON Summary.,Background:,YM150, a new oral direct factor Xa inhibitor is used as prophylaxis for venous thromboembolism (VTE), a well-known risk after orthopaedic surgery. Objectives:,To assess the safety and efficacy of thromboprophylaxis with YM150 in a dose escalation study. Patients/methods:,Patients (174) undergoing hip replacement surgery were randomized per cohort to oral once daily YM150 or subcutaneous enoxaparin (40 mg daily) in a 4:1 ratio for 7,10 days treatment. The YM150 doses were 3, 10, 30 and 60 mg by sequential four-dose escalation cohorts. The primary endpoint was major and/or clinically relevant non-major bleeding. The incidence of VTE was defined as a composite of verified symptomatic events and/or positive findings at bilateral venography on the last treatment day. An independent adjudication committee evaluated blindly the outcomes of the open-label study. Results:,No major and three clinically relevant non-major bleeds were reported, 1 (2.9%; 95% CI, 0.1,15.1) in the 3 mg and 2 (5.7%; 95% CI, 1.0,18.8) in the 10 mg YM150 dose groups. Of 147 patients (84%) with an evaluable venogram, VTE was observed in 51.9% (95% CI, 31.9,71.4), 38.7% (95% CI, 22.6,57.0), 22.6% (95% CI, 9.7,39.4), and 18.5% (95% CI, 7.5,36.5) in the YM150 dose groups 3, 10, 30 and 60 mg, respectively. A significant YM150 dose-related trend in VTE incidence was found (P=0.006). VTE with enoxaparin was 38.7% (95% CI, 22.6,57.0). Conclusions:,YM150, 10,60 mg daily, starting 6,10 h after primary hip replacement, was shown to be safe, well tolerated and effective. [source] | ||||||||||