Safety and efficacy of verinurad, a selective URAT1 inhibitor, for the treatment of patients with gout and/or asymptomatic hyperuricemia in the United States and Japan: Findings from two phase II trials

Abstract

Objective: Evaluate efficacy/safety of verinurad monotherapy in patients with gout (Japan/US) or asymptomatic hyperuricemia (Japan).

Methods: Two randomized, placebo-controlled, phase II studies were conducted (NCT01927198/NCT02078219). Patients were randomized to once-daily doses of placebo or escalating doses of verinurad (study 1: 5–12.5 mg; study 2: 2.5–15 mg). Primary endpoint was percentage change from baseline in serum urate (sUA) at week 12 (study 1)/week 16 (study 2). Safety was also assessed.

Results: Most patients in study 1 (n = 171) were white (74.9%); all patients were Japanese in study 2 (n = 204). Least squares means (±SE) estimate of percentage change in sUA levels from baseline in study 1 was 1.2 ± 2.9 for placebo, and –17.5 ± 2.8, –29.1 ± 2.8, –34.4 ± 2.9 for verinurad 5, 10, 12.5 mg, respectively. In study 2, results were –2.4 ± 2.5 and –31.7 ± 2.5, –51.7 ± 2.6,–55.8 ± 2.5, respectively. Difference from placebo was significant for each verinurad dose (p<.0001). The proportion of patients with treatment-emergent adverse events (TEAEs) was similar across all groups. Renal-related TEAEs were more common with verinurad than placebo.

Conclusion: Verinurad monotherapy resulted in sustained reductions in sUA in Japanese/US patients but renal AEs occurred, so verinurad alone is not recommended for treatment of hyperuricemia or gout. The renal consequences of excessive uric acid excretion deserve study.

Keywords:

• Asymptomatic hyperuricemia
• gout
• selective uric acid reabsorption inhibitor
• serum urate
• verinurad

Acknowledgments

We thank the investigators for inclusion and care of patients during the study. Editorial support for this manuscript was provided by Tom Claus of PAREXEL, which was funded by AstraZeneca. The study sponsor had a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; and review and approval of the manuscript.

Conflict of interest

Jesse Hall, Zancong Shen, Sha Liu, and Scott Baumgartner are former employees of Ardea Biosciences, Inc., a member of the AstraZeneca group. Yasushi Ito was a consultant to Ardea Biosciences, Inc. David Fitz-Patrick, Kent Roberson, Kiyoshi Niwa, Takabumi Fujimura, and Koji Mori received study funding from Ardea Biosciences, Inc.

Additional information

Funding

This clinical study was funded by Ardea Biosciences, Inc., a member of the AstraZeneca group.