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- Title
URC102, a potent and selective inhibitor of hURAT1, reduced serum uric acid in healthy volunteers.
- Authors
Lee, Hyun A.; Yu, Kyung-Sang; Park, Sang-In; Yoon, Seonghae; Onohara, Makoto; Ahn, Youngjoo; Lee, Howard
- Abstract
Objective URC102, a novel and potent inhibitor of human uric acid transporter 1 (hURAT1), is currently under clinical development to treat patients with gout. We performed a randomized, double-blind, placebo-controlled, phase I study to evaluate the safety, tolerability, pharmacodynamic, and pharmacokinetic profiles of URC102 after single and multiple oral administration in healthy male subjects. Methods Thirty-one Koreans and 23 Caucasians received a single dose of URC102 at 1–30 mg and 1–10 mg, respectively, while 44 Koreans received URC102 once-daily for 7 days at 1–20 mg. We evaluated safety and tolerability throughout the study, and serially determined serum uric acid, the fractional excretion of uric acid and URC102 concentrations. Results URC102 was well tolerated over the dose range of 1–10 mg after single and multiple administration. URC102 rapidly reduced serum uric acid, which was maintained over the entire treatment period. Furthermore, URC102 increased the area-under-the-effect curve over 168 h for fractional excretion of uric acid in a dose-dependent manner. The maximum plasma concentration and the area under the plasma concentration–time curve of URC102 increased dose-proportionally. The pharmacokinetic and pharmacodynamics characteristics of URC102 were similar in Koreans and Caucasians. Conclusion URC102 was safe and effectively lowered serum uric acid, which should be tested and confirmed in patients with hyperuricaemia and/or gout through further studies. Trial registration ClinicalTrials.gov, www.clinicaltrials.gov , NCT01953497 and NCT02524678.
- Subjects
DRUG tolerance; DOSE-effect relationship in pharmacology; GOUT; HYPERURICEMIA; ORAL drug administration; URIC acid; WHITE people; RANDOMIZED controlled trials; TREATMENT effectiveness; URICOSURIC agents; TREATMENT duration; PHARMACODYNAMICS
- Publication
Rheumatology, 2019, Vol 58, Issue 11, p1976
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/kez140