Efficacy and Safety of Febuxostat Extended and Immediate Release in Patients With Gout and Renal Impairment: A Phase III Placebo-Controlled Study

Objective To assess the efficacy and safety of febuxostat extended release (XR) and immediate release (IR) in patients with gout and normal or impaired renal function. Methods This was a 3-month, phase III, multicenter, double-blind, placebo-controlled study. Patients (n = 1,790) with a history of gout and normal or impaired (mild-to-severe) renal function were randomized to receive placebo, febuxostat IR 40 or 80 mg, or febuxostat XR 40 or 80 mg once daily (1:1:1:1:1 ratio). End points included proportions of patients with a serum urate (UA) level of <5.0 mg/dl at month 3 (primary end point), a serum UA level of <6.0 mg/dl at month 3, and >= 1 gout flare requiring treatment over 3 months (secondary end points). Results Both febuxostat formulations led to significantly greater proportions of patients achieving a serum UA level of <5.0 mg/dl or <6.0 mg/dl at month 3 (P < 0.001 for all comparisons versus placebo). Equivalent doses of febuxostat XR and IR had similar treatment effects on serum UA level end points; however, a significantly greater proportion of patients achieved a serum UA level of XR 40 mg versus IR 40 mg. Similar proportions of patients experienced >= 1 gout flare across treatment groups. Rates of treatment-emergent adverse events were low and evenly distributed between treatment arms. A preplanned subgroup analysis demonstrated that febuxostat formulations were well tolerated and generally effective on serum UA level end points (versus placebo) across all renal function subgroups. Conclusion Both formulations of febuxostat (XR and IR) were well tolerated and effective in patients with gout and normal or impaired renal function, including patients with severe renal impairment.