Abstract
The objective of the study was to evaluate the effect of lesinurad, a selective uric acid uptake inhibitor, alone and in combination with the xanthine oxidase inhibitor allopurinol, on serum uric acid and urinary urate excretion in patients with gout and hyperuricemia. A phase 1b, multicenter, open-label, multiple-dose study was carried out in patients with gout with serum uric acid ≥8 mg/dL following washout of urate-lowering therapy. Patients were treated with allopurinol 300 mg/day alone in week 1; lesinurad 400 or 600 mg/day was added in week 2, followed by lesinurad 400 or 600 mg/day alone in week 3. Serum uric acid and urine uric acid were evaluated each week. Safety was assessed throughout the study. Lesinurad 400 or 600 mg/day added to allopurinol 300 mg/day reduced serum uric acid by 60% and 72%, respectively, versus allopurinol alone (37%) or lesinurad 400 mg/day (44%) or 600 mg/day (47%) alone. A 100% response rate of serum uric acid <6 mg/dL was achieved by all combinations (serum uric acid <5 mg/dL by 50%-90%). Mean 24-hour urate excretion compared with baseline was -35% with allopurinol, +36% and +56.5% with lesinurad 400 mg/day and 600 mg/day, respectively, and -11.6% and -7.1% with the respective combination therapies. Treatments were well tolerated. In this phase 1 trial, lesinurad added to allopurinol resulted in greater serum uric acid reduction than did allopurinol or lesinurad monotherapy.