FRI0333 Lesinurad, a Selective Uric Acid Reabsorption Inhibitor, in Combination with Allopurinol: Results from a Phase III Study in Gout Patients Having an Inadequate Response to Standard of Care (Clear 2)
Authors: T. Bardin, R. Keenan, P. Khanna, J. Kopicko, M. Fung, N. Bhakta, S. Adler, C. Storgard, S. Baumgartner, A. So
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Lesinurad (RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for treatment of gout in combination with xanthine oxidase inhibitors. <h3>Objectives</h3> Assess efficacy and safety of lesinurad in combination with allopurinol (ALLO) in gout patients with inadequate response to standard of care (SOC) ALLO dosing (NCT01493531). <h3>Methods</h3> CLEAR 2 was a 12-month, randomized, double-blind, global phase III trial to evaluate lesinurad (200 mg or 400 mg oral, qd) in combination with ALLO vs ALLO+placebo (PBO). Patients were ages 18-85 yrs on stable, medically appropriate SOC ALLO doses ≥300 mg (≥200 mg in moderate renal impairment), as determined by investigator, with serum uric acid (sUA) ≥6.5 mg/dL at screening and ≥2 gout flares in prior 12 months. Primary endpoint was proportion of patients meeting sUA target of &lt;6.0 mg/dL (&lt;360 μmol/L) by Month 6. Secondary endpoints included mean gout flare rate requiring treatment (GFRT; Month 6 through 12) and proportion of patients with complete resolution of ≥1 target tophus by Month 12. Safety assessments included treatment-emergent AEs and laboratory data. <h3>Results</h3> Patients (N=610) were mostly male (96.2%), mean ± SD age was 51.2±10.9 yrs, and duration since gout diagnosis was 11.5±9.3 yrs. Most patients (84.1%) received ALLO 300 mg (range: 200-900 mg) daily; 23.6% had tophi at screening (measurable target tophi at baseline, 15.9%) and baseline sUA was 6.90±1.19 mg/dL. Lesinurad at both doses in combination with ALLO significantly increased proportions of patients achieving sUA targets (&lt;6.0 mg/dL and &lt;5.0 mg/dL) vs ALLO+PBO at all visits, with more than twice as many patients achieving targets at Month 6 (Figure). No significant differences were observed between groups in mean rate of GFRT (Month 6 to 12) or patients with complete target tophus resolution (by Month 12). Safety data are reported in the Table. Serum creatinine (sCr) elevations were observed, resolving in most cases without interrupting study medication. <h3>Conclusions</h3> Lesinurad (200 or 400 mg) in combination with ALLO significantly increased the proportion of patients achieving sUA target at 6 months, with more than twice as many patients reaching goal of &lt;6.0 mg/dL vs ALLO+PBO. Lesinurad was generally well tolerated at lower dose, where AE profile was comparable to ALLO alone and 2.0x sCr elevations were reversible. Combination therapy with lesinurad and ALLO represents a potentially promising treatment option for gout patients who are inadequately controlled on ALLO. <h3>Acknowledgements</h3> Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca. <h3>Disclosure of Interest</h3> T. Bardin Grant/research support from: Ipsen, Menarini, Consultant for: AstraZeneca, Ipsen, Menarini, Novartis, Savient, Sobi, Takeda, R. Keenan Consultant for: AstraZeneca, Crealta Pharmaceuticals, Takeda, P. Khanna Speakers bureau: Takeda, J. Kopicko Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., M. Fung Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., N. Bhakta Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., S. Adler Employee of: AstraZeneca Pharmaceuticals, C. Storgard Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., S. Baumgartner Employee of: Ardea Biosciences, Inc., a member of the AstraZeneca Group., A. So Consultant for: Novartis, AstraZeneca, Menarini