Effect of Food on the Pharmacokinetics of Darexaban, an Oral Direct Factor Xa Inhibitor, in Healthy Japanese Subjects

Background: Darexaban is a potent direct factor Xa (FXa) inhibitor developed for prophylaxis of venous and arterial thromboembolic disease. This drug is rapidly and extensively metabolized to darexaban glucuronide (YM-222714), which is a pharmacologically active metabolite. The potential effects of food on the pharmacokinetics of darexaban glucuronide after darexaban administration were assessed in two studies. Methods: Both studies were conducted as open-label, two-way crossover studies. Healthy non-elderly Japanese male subjects received darexaban as a single 15 mg tablet (Study 1, n = 24) or a single 30 mg tablet (Study 2, n = 24). The geometric mean ratio (GMR) (fed/fasted) for AUC(last) and C-max were evaluated as primary parameters. Results: GMR(fed/fasted) for AUC(last) demonstrated slight decreases as 0.797 (90% CI: 0.758 - 0.838) in Study 1 and 0.821 (90% CI: 0.752 - 0.896) in Study 2. For C-max, the GMR was 0.908 (90%CI: 0.835 - 0.988) in Study 1 and 1.039 (90% CI: 0.953 - 1.131) in Study 2. There were no serious adverse events during the two studies. None was considered to be drug-related. Conclusion: These studies demonstrated that there was no clinically significant effect of food on the pharmacokinetics after administration of darexaban. We therefore conclude that darexaban can be administered without regard to food intake.