Journal Article

Lesinurad in combination with allopurinol: a randomised, double-blind, placebo-controlled study in patients with gout with inadequate response to standard of care (the multinational CLEAR 2 study)

Storgard, Chris, Kopicko, Jeff, Baumgartner, Scott, Bardin, Thomas, Keenan, Robert T, So, Alexander, Bhakta, Nihar, Khanna, Puja P, Adler, Scott, Fung, Maple

2017

Overview

ObjectivesDetermine the efficacy and safety of daily lesinurad (200 or 400 mg orally) added to allopurinol in patients with serum uric acid (sUA) above target in a 12-month, randomised, phase III trial.MethodsPatients on allopurinol ≥300 mg (≥200 mg in moderate renal impairment) had sUA level of ≥6.5 mg/dL (≥387 µmol/L) at screening and two or more gout flares in the prior year. Primary end point was the proportion of patients achieving sUA level of <6.0 mg/dL (<357 µmol/L) (month 6). Key secondary end points were mean gout flare rate requiring treatment (months 7 through 12) and proportions of patients with complete resolution of one or more target tophi (month 12). Safety assessments included adverse events and laboratory data.ResultsPatients (n=610) were predominantly male, with mean (±SD) age 51.2±10.90 years, gout duration 11.5±9.26 years and baseline sUA of 6.9±1.2 mg/dL (410±71 µmol/L). Lesinurad at 200 and 400 mg doses, added to allopurinol, significantly increased proportions of patients achieving sUA target versus allopurinol-alone therapy by month 6 (55.4%, 66.5% and 23.3%, respectively, p<0.0001 both lesinurad+allopurinol groups). In key secondary end points, there were no statistically significant treatment-group differences favouring lesinurad. Lesinurad was generally well tolerated; the 200 mg dose had a safety profile comparable with allopurinol-alone therapy. Renal-related adverse events occurred in 5.9% of lesinurad 200 mg+allopurinol, 15.0% of lesinurad 400 mg+allopurinol and 4.9% of allopurinol-alone groups, with serum creatinine elevation of ≥1.5× baseline in 5.9%, 15.0% and 3.4%, respectively. Serious treatment-emergent adverse events occurred in 4.4% of lesinurad 200 mg+allopurinol, in 9.5% of lesinurad 400 mg+allopurinol and in 3.9% of allopurinol-alone groups, respectively.ConclusionLesinurad added to allopurinol demonstrated superior sUA lowering versus allopurinol-alone therapy and lesinurad 200 mg was generally well tolerated in patients with gout warranting additional therapy.Trial registration numberNCT01493531.

• Publisher: Elsevier Limited,BMJ Publishing Group
• Subject: Adolescent / Adult / Aged / Aged, 80 and over / Allopurinol - adverse effects / Allopurinol - therapeutic use / Cardiovascular Diseases - chemically induced / Clinical and Epidemiological Research / Creatinine - blood / Double-Blind Method / Drug dosages / Drug Therapy, Combination - adverse effects / Female / Gout - blood / Gout - drug therapy / Gout Suppressants - adverse effects / Gout Suppressants - therapeutic use / Humans / Male / Middle Aged / Patients / Renal Insufficiency - blood / Renal Insufficiency - chemically induced / Retreatment / Rheumatism / Standard of care / Studies / Symptom Flare Up / Thioglycolates - administration & dosage / Thioglycolates - adverse effects / Thioglycolates - therapeutic use / Triazoles - administration & dosage / Triazoles - adverse effects / Triazoles - therapeutic use / Uric acid / Uric Acid - blood / Uricosuric Agents - administration & dosage / Uricosuric Agents - adverse effects / Uricosuric Agents - therapeutic use / Urine / Young Adult