An Open-label, Randomized, Active Comparator-Controlled, Adaptive Parallel-group Phase 2 Study to Assess the Safety and Efficacy of Multiple Doses of ISIS 416858 Administered Subcutaneously to Patients Undergoing Total Knee Arthroplasty

� To assess the safety and efficacy profile of ISIS 416858, including incidence of bleeding and VTE, in patients undergoing total knee arthroplasty � To assess a potential dose-response relationship of ISIS 416858 with respect to the reduction of VTE incidence in patients undergoing total knee arthroplasty