FRI0367 BCX4208 added to allopurinol increases response rates in patients with GOUT who fail to reach goal range serum uric acid on allopurinol alone: A randomized, double-blind, placebo-controlled trial:
Authors: M.A. Becker, A.S. Hollister, R. Terkeltaub, A. Waugh, A. Flynt, D. Fitz-Patrick, W. Sheridan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> BCX4208, a novel purine nucleoside phosphorylase inhibitor, blocks uric acid production at a step preceding xanthine oxidase and synergistically reduces serum urate concentration (sUA) in gout patients when combined with allopurinol<sup>1</sup>. <h3>Objectives</h3> To assess the sUA response to the addition of placebo or one of 4 doses of BCX4208 to 300 mg/d allopurinol in gout patients with sUA ≥6.0 mg/dL on allopurinol alone. Primary endpoint was the proportion of BCX4208-treated subjects achieving sUA goal range (&lt;6.0 mg/dL) at 12 weeks compared with placebo. <h3>Methods</h3> 278 adult subjects (M:F =266:12) with gout and sUA ≥6.0 mg/dL despite allopurinol 300 mg/d for at least 2 weeks were randomized and received oral placebo or BCX4208 5, 10, 20, or 40 mg/d for 12 weeks while continuing allopurinol 300 mg/d. On-study assessments were performed at 2, 4, 8, and 12 weeks of treatment. Subjects received colchicine 0.6 mg/d or naproxen 220 mg to 250 mg BID for gout flare prophylaxis. Data from subjects who received &gt;1 dose of study drug and had at least one on-study sUA assessment (modified intention-to-treat [mITT] population) were analyzed. Missing data were imputed using the last observation carried forward method. <h3>Results</h3> Demographic, comorbid, and gout characteristics of the study population were evenly distributed in the study arms. Mean (SD) age was 49 (10) years and BMI was 36 (7) kg/m<sup>2</sup> in the predominantly white (73%) population, with high prevalences of hypertension (58%), diabetes (16%), and hypercholesterolemia (39%). BCX4208 added to allopurinol 300 mg/d brought more patients to goal range sUA compared with placebo (Table). Differences between the BCX4208 5, 20, and 40 mg/d arms and placebo were significant. Five to 11% of subjects per arm experienced ≥1 gout flare during treatment. Frequency and severity of adverse events, including infections, were evenly distributed across dose groups. <h3>Conclusions</h3> Addition of BCX4208 to allopurinol 300 mg/d allows a significantly greater proportion of gout patients to achieve goal range sUA than addition of placebo. Twelve weeks of BCX4208 daily dosing is generally safe and well-tolerated when combined with allopurinol. <h3>References</h3> Hollister AS, et al. Ann Rheum Dis 2011; 70 (Suppl 3): 183 <h3>Disclosure of Interest</h3> M. Becker Consultant for: BioCryst, Takeda, Savient, URL/Pharma, Ardea, Regeneron, Metabolex, Isis, A. Hollister Employee of: BioCryst Pharmaceuticals, Inc., R. Terkeltaub Consultant for: BioCryst, Ardea, Regeneron, Novartis, A. Waugh Employee of: BioCryst Pharmaceuticals, Inc., A. Flynt Consultant for: BioCryst Pharmaceuticals, Inc., D. Fitz-Patrick Grant/Research support from: BioCryst Pharmaceuticals, Inc., W. Sheridan Employee of: BioCryst Pharmaceuticals, Inc.