title: Lesinurad in combination with allopurinol: results of a phase 2, randomised, double-blind study in patients with gout with an inadequate response to allopurinol.
abstract: OBJECTIVE
  To assess the efficacy and tolerability of lesinurad, an oral selective uric acid reabsorption inhibitor, in combination with allopurinol versus allopurinol alone in patients with gout and an inadequate response to allopurinol.
  
  
  METHODS
  Patients (N=227) with an inadequate response to allopurinol, defined as serum urate (sUA) ≥6 mg/dL on ≥2 occasions ≥2 weeks apart despite ≥6 weeks of allopurinol, were randomised 2:1 to 4 weeks of double-blind treatment with lesinurad (200, 400 or 600 mg/day) or matching placebo in combination with their prestudy allopurinol dose (200-600 mg/day). Colchicine prophylaxis for gout flares was required. The primary end point was percent reduction from baseline sUA levels at 4 weeks. A pharmacokinetic substudy was also conducted. Safety was assessed throughout.
  
  
  RESULTS
  Patients (n=208) received ≥1 dose of blinded medication. Lesinurad 200, 400 and 600 mg in combination with allopurinol produced significant mean percent reductions from baseline sUA of 16%, 22% and 30%, respectively, versus a mean 3% increase with placebo (p<0.0001, all doses vs placebo). Similar results were observed in patients with mild or moderate renal insufficiency (estimated creatinine clearance 30 to <90 mL/min). The incidence of ≥1 treatment-emergent adverse event was 46%, 48% and 54% with lesinurad 200, 400 and 600 mg, respectively, and 46% with placebo (most frequent, gout flares, arthralgia, headache and nasopharyngitis), with no deaths or serious adverse events.
  
  
  CONCLUSIONS
  Lesinurad achieves clinically relevant and statistically significant reductions in sUA in combination with allopurinol in patients who warrant additional therapy on allopurinol alone.
  
  
  BACKGROUND
  NCT01001338.
authors.affiliation: Rheumatology Division, Hospital Universitario Cruces, Barakaldo, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Perez-Ruiz
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Gilead Sciences, Foster City, California, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Sundy
authors.affiliation: Ardea Biosciences, San Diego, California, USA.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Miner
authors.affiliation: Ardea Biosciences, San Diego, California, USA Receptos, San Diego, California, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Cravets
authors.affiliation: Ardea Biosciences, San Diego, California, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Storgard
mesh_terms: D000328:Adult; D000493:Allopurinol / Q000008:administration & dosage*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006073:Gout / Q000188:drug therapy*; D006074:Gout Suppressants / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013864:Thioglycolates / Q000008:administration & dosage*; D016896:Treatment Outcome; D014230:Triazoles / Q000008:administration & dosage*
chemical_list: D006074:Gout Suppressants; D013864:Thioglycolates; D014230:Triazoles; C000593471:lesinurad; D000493:Allopurinol
keywords: Gout; Inflammation; Pharmacokinetics; Treatment