EXANTA® (ximelagatran) Tablets NDA 21-686 FDA Advisory Committee Briefing Document.

New Drug Application (NDA) 21-686, submitted by AstraZeneca LP (AstraZeneca), requests approval for the use of EXANTA® (ximelagatran) Tablets as: œ An oral 24-mg twice daily (bid) fixed dose for the long-term secondary prevention of venous thromboembolism (VTE) after standard treatment for an episode of acute VTE œ An oral 36-mg bid fixed dose initiated post-operatively for the prevention of VTE in patients undergoing total knee replacement (TKR) surgery œ An oral 36-mg bid fixed dose for the prevention of stroke and systemic thromboembolic complications associated with atrial fibrillation (AF). The Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) Division of Gastrointestinal and Coagulation Drug Products has requested that AstraZeneca participate in a Cardiovascular and Renal Drugs Advisory Committee review of this application. This briefing document has been prepared to support that review. In this briefing document, AstraZeneca will provide the information necessary to make an assessment of the benefit-risk profile for ximelagatran as an oral anticoagulant and antithrombotic based on comparisons of ximelagatran to warfarin and to placebo. To facilitate the evaluation, this document and the presentation to the committee will briefly address the following key areas in the ximelagatran development program: development objectives, efficacy, safety, the proposed patient Risk Minimization Action Plan (RiskMAP), and the benefit-risk profile of ximelagatran.