Background/Purpose: Data generated by Phase 1 and 2 studies suggest that the extended-release (XR) formulation of febuxostat (FBX) may provide equal or better reduction in serum urate level (sUA) in patients (pts) with gout, with reduced exposure (C_max and AUC), compared with an immediate-release (IR) formulation. This Phase 2 study was conducted to evaluate the efficacy and safety of FBX XR compared with FBX IR in pts with gout and moderate renal impairment.

Methods: In a Phase 2, multicenter, randomized, placebo-controlled, double-blind study, pts with gout (sUA ≥8.0 mg/dL, moderate renal impairment [estimated glomerular filtration rate ≥30 mL/min and <60 mL/min], and ≥1 gout flare within the previous 12 months) received placebo or FBX XR 40 mg, XR 80 mg, IR 40 mg, or IR 80 mg once daily for 3 months. The primary endpoint was the proportion of pts with sUA <5.0 mg/dL at Month 3. Secondary endpoints were proportions of pts with at least 1 flare requiring treatment during the 3-month treatment period and of pts with sUA <6.0 mg/dL at Month 3.

Results: A total of 189 pts received treatment with placebo (n=38) or FBX XR 40 mg (n=39), XR 80 mg (n=38), IR 40 mg (n=37), or IR 80 mg (n=37). A higher proportion of pts receiving FBX XR 40 mg achieved sUA <5.0 mg/dL versus (vs) IR 40 mg at Month 3 (35.9% vs 13.5%, respectively; p=0.034). All FBX groups showed a higher proportion of pts with at least 1 flare during treatment compared with placebo-treated pts, but a smaller proportion of pts in the FBX XR 40-mg group experienced flares compared with IR 40 mg (23.1% vs 40.5%, respectively). Additionally, a numerically higher proportion of pts achieved sUA <6 mg/dL with FBX XR 40 mg compared with IR 40 mg (53.8% vs 32.4%, respectively). FBX XR 80 mg did not differentiate from IR 80 mg for the primary or secondary endpoints. Primary and secondary endpoint results are shown (Figure). Treatment-emergent and treatment-related adverse events were infrequent and generally did not differ among treatment groups.

Conclusion: Significantly more pts receiving FBX XR 40 mg achieved the primary endpoint of sUA reduction to <5.0 mg/dL at the Month 3 visit compared with FBX IR 40 mg. There was a trend toward lower flare rates in the FBX XR 40 mg vs the IR 40 mg group. Overall, incidence rates of treatment-emergent and treatment-related adverse events were low.