A Series of Double-Blind, Placebo-Controlled, Randomized, Multicenter, Phase 2 Studies to Evaluate the Efficacy, Safety, and Dose-Response Relationship of Orally Administered URC102, a Novel URAT1 Inhibitor, in Korean Patients with Gout

Abstract

Background/Purpose:

URC102 is a novel URAT1 inhibitor under clinical development for the treatment of hyperuricemia with gout. A series of double-blind, placebo-controlled, randomized, multicenter, phase 2 studies investigated the efficacy, safety, and dose-response relationship of URC102 in patients with gout (NCT02290210 and NCT02557126).

Methods:

Korean male patients aged ≥20 and <70 years with gout and serum uric acid (sUA) levels ≥7.0 mg/dL and ≤10.0 mg/dL at screening were randomized to orally (QD) receive placebo or URC102 at 0.25 mg, 0.5 mg, 1 mg, and 2 mg (first study with low-dose URC102) and placebo or URC102 at 3 mg, 5mg, 7 mg, and 10 mg (second study with high-dose URC102) for 14 days. Efficacy was evaluated by analyzing the trend of sUA reduction, defined as percentage changes of sUA for 2 weeks with reference to baseline, after administration of URC102. Safety was assessed with adverse events (AEs), physical examinations, and laboratory findings throughout the studies.

Results:

Sixty-four (first study) and 76 (second study) patients with gout were randomized. The mean percentage changes (± standard deviation) of sUA on Day 15 was -3.96 (±15.77)%, -3.28 (±10.39)%, -10.63 (±10.09)%, -13.15 (±20.30)%, and -29.52 (±8.45)% in the placebo, URC102 0.25 mg, 0.5 mg, 1 mg, and 2 mg groups, respectively (first study), and -1.20 (±7.75)%, -28.31 (±15.17)%, -44.02 (±20.11)%, -49.05 (±10.76)%, and -54.31 (±12.38)% in the placebo, URC102 3 mg, 5 mg, 7 mg, and 10 mg groups, respectively (second study). AEs that occurred with a frequency of 10% or more, regardless of causality, were arthralgia and pain in extremity (first study) and gout and arthralgia (second study). Most of the AEs were mild in severity, and there were no significant differences in the frequency of AEs between the placebo and URC102 treatment groups. Two serious AEs, animal bite and traffic accident, were reported, but the causality to the study drug was unrelated in both events.

Conclusion:

URC102 decreased sUA levels in a dose-dependent manner in Korean patients with gout. All doses of orally administered URC102 for 14 days were well tolerated. Further long-term clinical studies in larger populations are warranted to evaluate the effectiveness of URC102, which could be a new effective treatment option as a urate-lowering therapy.