This excerpt taken from the ARYX 8-K filed Jul 8, 2009.
Our Study Design and Implementation
EmbraceAC enrolled 612 patients at 48 clinical study sites in the United States. It was a randomized, double-blind, parallel group, active control study comparing tecarfarin with warfarin in patients who require chronic, oral anticoagulation. The patients who entered this study required anticoagulation therapy to avoid serious blood clotting resulting from their underlying conditions. Each patient was treated for a minimum of six months on either tecarfarin or warfarin and the patients and study site investigators were blind to therapy and dose. Patients included in the study had a variety of underlying conditions including atrial fibrillation; an implanted prosthetic heart valve; a history of venous thromboembolic disease (DVT/PE); a history of myocardial infarction or cardiomyopathy. This is the same patient population for which warfarin is indicated for use and that tecarfarin is intended to treat.
The same target therapeutic range of INR of 2.0 to 3.0 (for heart valve patients the target range applied was 2.5 to 3.5) was applied for patients receiving warfarin therapy as those administered tecarfarin. The primary endpoint of the trial was to demonstrate that patients are maintained within the target INR range a higher percentage of the time when treated with tecarfarin than with warfarin.
The dosing of patients and monitoring of their anticoagulation status was entirely and independently controlled by a central dose control center comprised of clinicians experienced in managing anticoagulation therapy. Since the center was unblinded to each patients therapy, history and INR status, factors known to compromise warfarins efficacy, including concomitant medications, frequency of INR monitoring and a patients genotype, were actively taken into account at time of dosing. Genotype data gives the physician information about the rate at which patients metabolize warfarin. In particular, the CYP2C9
genotype was evaluated to distinguish between wild type patients with normal rates of warfarin metabolism and patients with a CYP2C9 variant who have slower metabolism. Similar information was gathered on patients VKORC1 genotype. Widely published literature links the particular importance of adjusting warfarin dosing for patients who are either CYP2C9 or VKORC1 variants since they are prone to over-and under-anticoagulation.(Wadelius et al, Blood, 113(4), 784-792, 2009).