Effects of febuxostat versus allopurinol and placebo in reducing serum urate in subjects with hyperuricemia and gout: a 28-week, phase III, randomized, double-blind, parallel-group trial.

Objective: To compare the urate-lowering efficacy and safety of febuxostat, allopurinol, and placebo in a large group of subjects with hyperuricemia and gout, including persons with impaired renal function.

Methods: Subjects (n = 1,072) with hyperuricemia (serum urate level > or = 8.0 mg/dl) and gout with normal or impaired (serum creatinine level >1.5 to < or = 2.0 mg/dl) renal function were randomized to receive once-daily febuxostat (80 mg, 120 mg, or 240 mg), allopurinol (300 or 100 mg, based on renal function), or placebo for 28 weeks.

Results: Significantly (P < or = 0.05) higher percentages of subjects treated with febuxostat 80 mg (48%), 120 mg (65%), and 240 mg (69%) attained the primary end point of last 3 monthly serum urate levels <6.0 mg/dl compared with allopurinol (22%) and placebo (0%). A significantly (P < 0.05) higher percentage of subjects with impaired renal function treated with febuxostat 80 mg (4 [44%] of 9), 120 mg (5 [45%] of 11), and 240 mg (3 [60%] of 5) achieved the primary end point compared with those treated with 100 mg of allopurinol (0 [0%] of 10). Proportions of subjects experiencing any adverse event or serious adverse event were similar across groups, although diarrhea and dizziness were more frequent in the febuxostat 240 mg group. The primary reasons for withdrawal were similar across groups except for gout flares, which were more frequent with febuxostat than with allopurinol.

Conclusion: At all doses studied, febuxostat more effectively lowered and maintained serum urate levels <6.0 mg/dl than did allopurinol (300 or 100 mg) or placebo in subjects with hyperuricemia and gout, including those with mild to moderately impaired renal function.