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 the immediate-release (IR) formulation. This Phase 3 study was conducted to evaluate the efficacy and safety of FBX XR compared with FBX IR in gout pts with normal or impaired renal function.

Methods: In a Phase 3, multicenter, randomized, placebo-controlled, double-blind study, pts with gout (sUA ≥8.0 mg/dL, estimated glomerular filtration rate ≥15 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 1783 pts received treatment with placebo (n=357) or FBX XR 40 mg (n=355), XR 80 mg (n=357), IR 40 mg (n=357), or IR 80 mg (n=357). A higher proportion of pts receiving FBX XR 40 mg achieved sUA <5.0 mg/dL versus (vs) IR 40 mg at Month 3 (25.9% vs 15.7%, respectively; p=0.001). Although the difference was not statistically significant, more FBX XR 80-mg treated pts achieved the primary endpoint compared with IR 80 mg (50.1% vs 42.6%, respectively). Neither FBX XR treatment group differentiated from its respective IR treatment group for the secondary endpoint of proportion of pts with at least 1 flare requiring treatment during the 3-month treatment period. A numerically higher proportion of pts achieved sUA <6.0 mg/dL with FBX XR 40 mg compared with IR 40 mg (48.2% vs 40.3%, respectively), and the observed difference between FBX XR 80 mg vs IR 80 mg for this endpoint was small (61.1% vs 57.7%, respectively). 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. Overall, the incidence rates of treatment-emergent and treatment-related adverse events were low. Both FBX formulations were efficacious in lowering sUA and were generally well tolerated.