medwireNews: Results of a phase IIa trial support further investigation of the selective URAT1 inhibitor verinurad in combination with febuxostat for the treatment of gout.
Roy Fleischmann (University of Texas, Dallas, USA) and co-investigators randomly assigned 64 patients with gout and serum uric acid levels of at least 8 mg/dL to receive daily treatment with oral verinurad at a dose of 2.5–20 mg in combination with febuxostat 40 mg or 80 mg, or to receive febuxostat 40 mg or 80 mg alone. The total treatment duration was 28 days.
Patients treated with verinurad and febuxostat experienced dose-dependent decreases in serum uric acid levels, with the maximum decrease from baseline occurring 8–12 hours after dosing. The maximum decrease ranged from 52% to 77% for patients given verinurad plus febuxostat 40 mg and from 62% to 82% for those taking verinurad plus the 80 mg dose of febuxostat. By comparison, patients given febuxostat 40 mg or 80 mg alone had a maximum decrease in serum uric acid levels of 42% and 55%, respectively.
These findings indicate that “[t]he combination of febuxostat with verinurad has the potential to lower [serum uric acid] to a greater extent than by either treatment alone,” say the study authors.
They add that verinurad at doses of at least 5 mg combined with febuxostat 40 mg lowered serum uric acid levels to a greater degree than febuxostat 80 mg alone, which is “indicative of a greater [pharmacodynamic] effect for the combination than the higher dose of febuxostat monotherapy.”
Analysis of urine samples indicated that the maximum rates of uric acid excretion in the urine at 12–24 hours after dosing were comparable to baseline levels in patients receiving combination treatment, but were lower than at baseline among those given febuxostat alone, which the authors suggest may be due to febuxostat-mediated lowering of urate production.
“These observations suggest that the risk of uric acid crystallisation, manifesting as acute urate nephropathy and/or increased risk for nephrolithiasis, can be reduced or eliminated by co-administering febuxostat with verinurad,” they write in RMD Open.
Fleischmann and team report that verinurad was “well tolerated with no clinically meaningful changes in laboratory values.” Approximately a third of participants reported treatment-emergent adverse events, which were all mild or moderate in severity with the exception of one incidence of severe hypertriglyceridemia in a patient receiving febuxostat 80 mg alone.
Taken together, these results “support continued investigation of oral verinurad in a dual-mechanism approach to lowering [serum uric acid],” conclude the researchers.
medwireNews is an independent medical news service provided by Springer Healthcare. © 2018 Springer Healthcare part of the Springer Nature group