Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study

التفاصيل البيبلوغرافية
العنوان: Pharmacodynamic and pharmacokinetic effects and safety of verinurad in combination with febuxostat in adults with gout: a phase IIa, open-label study
المؤلفون: Roy, Fleischmann, Peter, Winkle, Jesse, Hall, Shakti, Valdez, Sha, Liu, Xiaohong, Yan, Liz, Hicks, Caroline, Lee, Jeffrey N, Miner, Michael, Gillen, Martha, Hernandez-Illas
المصدر: RMD Open
سنة النشر: 2018
مصطلحات موضوعية: gout, verinurad, Crystal Arthropathies, febuxostat
الوصف: Objective Verinurad (RDEA3170) is a high-affinity, selective URAT1 inhibitor in development for treating gout and asymptomatic hyperuricaemia. This study evaluated the pharmacodynamics, pharmacokinetics and safety of verinurad in combination with febuxostat in adults with gout. Methods The phase IIa, open-label, multicentre study randomised 64 subjects into one of five cohorts to receive febuxostat (40 or 80 mg) alone or in combination with verinurad 2.5–20 mg. Serial plasma/serum and urine samples were assayed for verinurad and uric acid. Safety was assessed by adverse events, chemistry panels, ECGs and physical examinations. Results Serum pharmacodynamic data demonstrated the maximum percent decrease in serum urate (sUA) from baseline (Emax) at 8–12 hours after dosing. Verinurad with febuxostat decreased sUA in a dose-dependent manner. Emax for verinurad with febuxostat 40 mg ranged from 52% to 77% vs 42% for febuxostat 40 mg alone; Emax for verinurad with febuxostat 80 mg was 62%–82% vs 55% for febuxostat 80 mg alone. Urinary uric acid excretion rate was reduced below baseline by febuxostat alone and was comparable to baseline for verinurad with febuxostat. Verinurad plasma exposure increased with dose and was comparable when combined with febuxostat. No drug-drug interactions were observed. Verinurad was well tolerated with no clinically meaningful changes in laboratory values. Conclusion Verinurad administered with febuxostat produced dose-dependent decreases in sUA while maintaining urinary uric acid levels comparable to baseline. These dose combinations of verinurad and febuxostat were generally well tolerated. These data support continued investigation of oral verinurad in patients with gout. Trial registration number NCT02246673
تدمد: 2056-5933
URL الوصول: https://explore.openaire.eu/search/publication?articleId=pmid________::c9b432d0c1166012a2830b24c91aeb77
https://pubmed.ncbi.nlm.nih.gov/29657831
Rights: OPEN
رقم الانضمام: edsair.pmid..........c9b432d0c1166012a2830b24c91aeb77
قاعدة البيانات: OpenAIRE