Daiichi Sankyo reports promising results from Phase II AF study

The objective of the multinational study was to assess the safety of four dose regimens of DU-176b in patients with non-valvular atrial fibrillation (AF), as compared to warfarin.

A total of 1,146 patients with atrial fibrillation with a CHADS2 index greater than or equal to two were enrolled in the study. Patients were randomly assigned to receive either one of the four fixed dose regimens of DU-176b (30mg/N=235 or 60mg/N=234 administered once daily; 30mg/N=244 or 60mg/N=180 administered twice daily), or warfarin (N=250) dose-adjusted locally to a target international normalized ratio (INR) of 2.0-3.0 for 12 weeks. The INR was determined weekly for four weeks and every two weeks thereafter.

The primary endpoints of the study were the incidence of bleeding events and elevated liver enzymes or bilirubin. The incidence of major and clinically relevant non-major bleeding events was significantly higher with the 30mg and 60mg twice-daily DU-176b regimens (7.8%, p = 0.029 and 10.6%, p = 0.002 respectively) than it was in patients given warfarin (3.2%).

In contrast, the incidence of major and clinically relevant non-major bleeding events with the 30 and 60mg once-daily DU-176b regimens was comparable to that with warfarin (3%, 3.8% and 3.2%, respectively).

There were no significant differences in the numbers of patients with elevated liver enzymes or bilirubin across all treatment groups. Although the study was not powered to detect efficacy, there were no significant differences in the rates of secondary endpoints across treatment groups, the company said.