Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
Rheumatology (Oxford). 2019 Nov 1;58(11):1976-1984. doi: 10.1093/rheumatology/kez140.
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.
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.
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.
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.
ClinicalTrials.gov, www.clinicaltrials.gov, NCT01953497 and NCT02524678.
URC102 是一种新型、强效的人尿酸转运蛋白 1（hURAT1）抑制剂，目前正在临床开发中，用于治疗痛风患者。我们进行了一项随机、双盲、安慰剂对照、I 期研究，以评估 URC102 在健康男性中的单次和多次口服给药的安全性、耐受性、药效学和药代动力学特征。
31 名韩国人和 23 名白种人分别接受了 1-30mg 和 1-10mg 的单剂量 URC102，而 44 名韩国人则接受了 1-20mg 的 URC102 每日一次给药 7 天。我们在整个研究过程中评估了安全性和耐受性，并连续测定了血清尿酸、尿酸的分数排泄和 URC102 的浓度。
URC102 在单次和多次给药的 1-10mg 剂量范围内具有良好的耐受性。URC102 迅速降低了血清尿酸水平，在整个治疗期间得到维持。此外，URC102 以剂量依赖的方式增加了尿酸分数排泄的效应曲线下面积超过 168 小时。URC102 的最大血浆浓度和血浆浓度-时间曲线下面积与剂量呈比例增加。URC102 的药代动力学和药效学特征在韩国人和白种人之间相似。
URC102 是安全的，能有效降低血清尿酸水平，这应通过进一步的研究在高尿酸血症和/或痛风患者中进行测试和确认。
ClinicalTrials.gov，www.clinicaltrials.gov，NCT01953497 和 NCT02524678。
