Efficacy and safety of a selective URAT1 inhibitor SHR4640 in Chinese subjects with hyperuricemia: a randomized controlled phase II study.

OBJECTIVES To evaluate the efficacy and safety of SHR4640, a highly selective urate transporter 1 inhibitor in Chinese subjects with hyperuricemia. METHODS This was a randomized double-blind dose-ranging phase II study. Subjects whose serum uric acid levels ≥480 µmol/l with gout, or sUA levels ≥480 µmol/l without gout but with comorbidities, or sUA levels ≥540 µmol/l were enrolled. Subjects were randomly assigned (1:1:1:1:1) to receive once daily 2.5 mg/5 mg/10 mg of SHR4640, 50 mg of benzbromarone, and placebo, respectively. The primary end point was the proportion of subjects achieved target sUA level of ≤ 360 µmol/l at week 5. RESULTS About 99.5% of subjects (n = 197) were male and 95.9% of subjects had gout history. The proportions of subjects achieved target sUA at week 5 were 32.5%, 72.5% and 61.5% in 5 mg, 10 mg of SHR4640 and benzbromarone groups, respectively, significantly higher than placebo group (0%; p< 0.05 for 5 mg and 10 mg of SHR4640 group). The sUA was reduced by 32.7%, 46.8% and 41.8% at week 5 with 5 mg, 10 mg of SHR4640 and benzbromarone, respectively, vs placebo (5.9%; p< 0.001 for each comparison). The incidences of gout flares requiring intervention were similar among all groups. Occurrences of treatment-emergent adverse events (TEAEs) were comparable across all groups, and serious TEAEs were not reported. CONCLUSIONS The present study indicated a superior sUA-lowering effect, and well tolerated safety profile after 5-week treatment with once-daily 5 mg/10 mg of SHR4640 as comparing with placebo in Chinese subjects with hyperuricemia. TRIAL REGISTRATION ClinicalTrials.gov number, NCT03185793.