Background Lesinurad (LESU; RDEA594) is a selective uric acid reabsorption inhibitor (SURI) being investigated for the treatment of gout in combination with a xanthine oxidase inhibitor (XOI).
Objectives LIGHT is a multinational randomized, double-blind, placebo-controlled, 6-month phase III clinical trial to determine the efficacy and safety of LESU 400mg monotherapy in patients intolerant to an XOI (NCT01508702).
Methods Gout patients with intolerance/contraindication to XOI and serum uric acid (sUA) ≥6.5 mg/dL were randomized to LESU (400mg oral, once daily) or placebo (PBO). The primary endpoint was the proportion of patients with sUA <6.0 mg/dL at Month 6. Safety assessments included treatment-emergent adverse events (TEAEs) and laboratory data. Patients who completed the study were eligible to enroll in an open-label, uncontrolled extension study of LESU 400 mg monotherapy (NCT01650246).
Results Patients (LESU, 107; PBO, 107) were primarily white (81.8%) and male (91.1%) with mean ± SD age of 54.4±12.3 years, 11.2±8.7 years since gout diagnosis, 6.2±7.3 gout flares in past 12 months, tophi (25% of patients), renal impairment (58.9% with estimated creatinine clearance [eCrCL] <90 mL/min), and sUA of 9.3±1.5 mg/dL. Patients had intolerance/contraindication to allopurinol (91.1%), febuxostat (8.9%) or both (4.2%). Significantly more patients achieved the primary endpoint (sUA <6.0 mg/dL at Month 6) with LESU 400mg than PBO (29.9% vs.1.9%; Figure). Discontinuation rate was greater with LESU 400mg (32.7%) than PBO (15.9%). Overall AE rate was higher with LESU 400mg, mainly due to more renal AEs (Table). Of the 143 patients (PBO, 78; LESU, 65) who enrolled in the extension study, 84 (59%) and 35 (24%) completed 6 and 12 months, respectively, prior to early study termination by the Sponsor (mean LESU exposure, 223 days). A total of 91 patients (64%) achieved sUA <6.0 mg/dL at some point during the extension study. AEs were similar to the LESU 400mg group in the core study (Table).
Conclusions In this multinational study of gout patients with high sUA and intolerance/contraindication to an XOI, nearly one third of patients treated with LESU 400 mg achieved sUA <6 mg/dL at 6 months. Renal AEs were more frequent with LESU 400mg monotherapy.
Acknowledgements Research sponsored by Ardea Biosciences/AstraZeneca. Editorial support was provided by PAREXEL and funded by AstraZeneca.
Disclosure of Interest A.-K. Tausche Consultant for: Menarini, Ipsen, Novartis, Savient, AstraZeneca, Speakers bureau: Menarini, Ipsen, Novartis, Savient, AstraZeneca, R. Alten Grant/research support from: AstraZeneca, N. Dalbeth Grant/research support from: AstraZeneca, Fonterra, Novartis, Consultant for: AstraZeneca, Fonterra, Takeda, Metabolex, Speakers bureau: Savient, Menarini, Novartis, Takeda, J. Kopicko Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, N. Bhakta Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, C. Storgard Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, S. Baumgartner Employee of: Ardea Bisociences, Inc., a member of the AstraZeneca group, K. Saag Grant/research support from: Ardea/AstraZeneca, Crealta, Takeda, Consultant for: Amgen, Ardea/AstraZeneca, CORONA, Crealta
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