• Roy Fleischmann, Bradley Kerr, Li-Tain Yeh, Matt Suster, Zancong Shen, Elizabeth Polvent, Vijay Hingorani, Barry Quart, Kimberly Manhard, Jeffrey N Miner, Scott Baumgartner, and RDEA594-111 Study Group.
• Metroplex Clinical Research Center, Dallas, TX, Ardea Biosciences and Translational Sciences Department, Clinical Department, Regulatory Department and Biology Department, Ardea Biosciences, San Diego, CA, USA. rfleischmann@mcrcdallas.com.
• Rheumatology (Oxford). 2014 Dec 1; 53 (12): 2167-74.

ObjectiveThe aim of this study was to evaluate the pharmacodynamics (PDs), pharmacokinetics (PKs) and safety of lesinurad (selective uric acid reabsorption inhibitor) in combination with febuxostat (xanthine oxidase inhibitor) in patients with gout.MethodsThis study was a phase IB, multicentre, open-label, multiple-dose study of gout patients with serum uric acid (sUA) >8 mg/dl following washout of urate-lowering therapy with colchicine flare prophylaxis. Febuxostat 40 or 80 mg/day was administered on days 1-21, lesinurad 400 mg/day was added on days 8-14 and then lesinurad was increased to 600 mg/day on days 15-21. sUA, urine uric acid and PK profiles were evaluated at the end of each week. Safety was assessed by adverse events, laboratory tests and physical examinations.ResultsInitial treatment with febuxostat 40 or 80 mg/day monotherapy resulted in 67% and 56% of subjects, respectively, achieving a sUA level <6 mg/dl. Febuxostat 40 or 80 mg/day plus lesinurad 400 or 600 mg/day resulted in 100% of subjects achieving sUA <6 mg/dl and up to 100% achieving sUA <5 mg/dl. No clinically relevant changes in the PKs of either drug were noted. The combination was well tolerated.ConclusionThe clinically important targets of sUA <6 mg/dl and <5 mg/dl are achievable in 100% of patients when combining lesinurad and febuxostat.© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

43 keywords...

hide…