The Effect of Lesinurad in Combination With Allopurinol on Serum Uric Acid Levels in Patients With Gout. (7th May 2018)

• Record Type: Journal Article
• Authors: Baumgartner, Scott; Yeh, Li‐Tain; Shen, Zancong; Kerr, Bradley; Manhard, Kimberly; Quart, Barry
• Is Part Of: Journal of clinical pharmacology. Volume 58:Number 9(2018)
• Page Start: 1164
• Page End: 1170
• Publication Date: 2018-05-07
• Subjects: allopurinol -- combination -- gout -- lesinurad -- serum urate -- xanthine oxidase inhibitor; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Pharmacology, Clinical -- Periodicals; 615.1
• DOI: 10.1002/jcph.1124
• Languages: English
• ISSNs: 0091-2700

Abstract

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.