BACKGROUND: The short-term safety and plasma concentrations of edoxaban 15 mg once daily in Japanese patients with non-valvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CL<inf>CR</inf>;] ≥15 to <30 ml/min) were compared with those in NVAF patients with normal renal function or mild renal impairment (normal/MiRI; CL<inf>CR</inf>≥50 ml/min) treated with edoxaban 30 or 60 mg. METHODS AND RESULTS: In this Phase 3 multicenter open-label 3 parallel-group study, SRI patients received once-daily edoxaban15 mg (n=50), whereas normal/MiRI patients were randomized to receive either once-daily edoxaban 30 or 60 mg (n=22 and 21, respectively) for 12 weeks. Plasma edoxaban concentrations and biomarkers of blood coagulation and fibrinolysis were measured. Adverse events and thromboembolic events were recorded throughout the study. Rates of any bleeding were comparable between SRI patients receivingedoxaban 15 mg (20.0%) and normal/MiRI patients receiving edoxaban 30 or 60 mg (22.7% and 23.8%, respectively). No major bleeding or thromboembolic events occurred in any treatment group. Similar plasma concentrations and biomarker profiles were observed in SRI patients receivingedoxaban 15 mg and normal/MiRI patients receiving edoxaban 30 or 60 mg. CONCLUSIONS: In this 12-week short-term study in Japanese NVAF patients withSRI, edoxaban 15 mg once daily exhibited similar safety, plasma concentration, and biomarker profiles as did the 30-mg and 60-mg doses in patients with normal/MiRI.
RCT Entities:
BACKGROUND: The short-term safety and plasma concentrations of edoxaban 15 mg once daily in Japanese patients with non-valvular atrial fibrillation (NVAF) and severe renal impairment (SRI; creatinine clearance [CL<inf>CR</inf>] ≥15 to <30 ml/min) were compared with those in NVAF patients with normal renal function or mild renal impairment (normal/MiRI; CL<inf>CR</inf>≥50 ml/min) treated with edoxaban 30 or 60 mg. METHODS AND RESULTS: In this Phase 3 multicenter open-label 3 parallel-group study, SRI patients received once-daily edoxaban 15 mg (n=50), whereas normal/MiRI patients were randomized to receive either once-daily edoxaban 30 or 60 mg (n=22 and 21, respectively) for 12 weeks. Plasma edoxaban concentrations and biomarkers of blood coagulation and fibrinolysis were measured. Adverse events and thromboembolic events were recorded throughout the study. Rates of any bleeding were comparable between SRI patients receiving edoxaban 15 mg (20.0%) and normal/MiRI patients receiving edoxaban 30 or 60 mg (22.7% and 23.8%, respectively). No major bleeding or thromboembolic events occurred in any treatment group. Similar plasma concentrations and biomarker profiles were observed in SRI patients receiving edoxaban 15 mg and normal/MiRI patients receiving edoxaban 30 or 60 mg. CONCLUSIONS: In this 12-week short-term study in Japanese NVAF patients with SRI, edoxaban 15 mg once daily exhibited similar safety, plasma concentration, and biomarker profiles as did the 30-mg and 60-mg doses in patients with normal/MiRI.