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:

Background

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 allopurinol¹.

Objectives

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 (<6.0 mg/dL) at 12 weeks compared with placebo.

Methods

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 >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.

Results

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/m² 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.

Conclusions

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.

References

Hollister AS, et al. Ann Rheum Dis 2011; 70 (Suppl 3): 183

Disclosure of Interest

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.