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- Title
Verinurad combined with febuxostat in Japanese adults with gout or asymptomatic hyperuricaemia: a phase 2a, open-label study.
- Authors
Shiramoto, Masanari; Liu, Sha; Shen, Zancong; Yan, Xiaohong; Yamamoto, Amy; Gillen, Michael; Ito, Yasushi; Hall, Jesse
- Abstract
Objectives Verinurad (RDEA3170) is a high-affinity inhibitor of the URAT1 transporter in clinical development for treating gout and asymptomatic hyperuricaemia. The aim of this Phase 2a, randomized, open-label study was to investigate the multiple-dose pharmacodynamics, pharmacokinetics and safety of oral verinurad combined with febuxostat vs febuxostat alone and verinurad alone. Methods Japanese male subjects aged 21–65 years with gout (n = 37) or asymptomatic hyperuricaemia (n = 35) and serum urate (sUA) ⩾8 mg/dl were randomized to febuxostat (10, 20, 40 mg) in combination with verinurad (2.5–10 mg), verinurad alone (2.5–15 mg), febuxostat alone (10, 20, 40 mg) or benzbromarone alone (50 mg). There were four treatment periods per cohort and each treatment period was 7 days. Study drugs were administered once-daily after breakfast. Plasma, serum and urine samples were measured at pre-set intervals on days –1, 7, 14, 21 and 28. Results Verinurad combined with febuxostat decreased sUA in dose-dependent manner, providing greater sUA lowering than febuxostat alone at the same dose (P < 0.001). Urinary uric acid excretion rate was increased by verinurad, reduced by febuxostat and comparable to baseline for verinurad combined with febuxostat. Verinurad from 2.5 mg to 15 mg was well tolerated, with no withdrawals due to adverse events. Laboratory assessments showed no clinically meaningful changes during combination treatment. Conclusion Verinurad combined with febuxostat decreased sUA dose-dependently while maintaining uric acid excretion similar to baseline. All dose combinations of verinurad and febuxostat were generally well tolerated. These data support continued investigation of oral verinurad in patients with gout. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov, NCT02317861
- Subjects
JAPAN; BREAKFASTS; COMBINATION drug therapy; GOUT; HYPERURICEMIA; JAPANESE people; JOINTS (Anatomy); LONGITUDINAL method; ORAL drug administration; THIAZOLES; UREA; URIC acid; RANDOMIZED controlled trials; URICOSURIC agents; CHEMICAL inhibitors; PHARMACODYNAMICS
- Publication
Rheumatology, 2018, Vol 57, Issue 9, p1602
- ISSN
1462-0324
- Publication type
Article
- DOI
10.1093/rheumatology/key100