URC102, a potent and selective inhibitor of hURAT1, reduced serum uric acid in healthy volunteers.
Rheumatology (Oxford)
; 58(11): 1976-1984, 2019 11 01.
Article
em En
| MEDLINE
| ID: mdl-31056705
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.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ácido Úrico
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Uricosúricos
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Transportadores de Ânions Orgânicos
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Proteínas de Transporte de Cátions Orgânicos
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Hidrocarbonetos Bromados
Tipo de estudo:
Clinical_trials
Limite:
Adult
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Humans
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Male
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article