Tigulixostat

Serum urate-lowering efficacy and safety of Tigulixostat in gout patients with hyperuricemia: a randomized, double-blind, placebo-controlled, dose-finding trial (CLUE)

Arthritis Rheumatol 2023 Jan 17.PMID:36649008DOI:10.1002/art.42447

Objective: To evaluate the safety and efficacy of the non-purine xanthine oxidase inhibitor Tigulixostat in lowering serum urate (sUA) levels in gout patients with hyperuricemia. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-finding phase II trial. After screening, gout patients with hyperuricemia were randomly assigned, after appropriate washout, to receive daily oral administration of 50 mg, 100 mg, or 200 mg of Tigulixostat or placebo for 12 weeks. Colchicine gout flare prophylaxis was administered to all subjects. The primary endpoint was the proportion of subjects with sUA levels <5.0 mg/dL at week 12. Results: A total of 143 subjects were randomized to receive Tigulixostat 50 mg (n=34), 100 mg (n=38), 200 mg (n=37), or placebo (n=34). A significantly greater proportion of subjects in the Tigulixostat dose groups (47.1% in the 50 mg, 44.7% in the 100 mg, and 62.2% in the 200 mg groups) achieved sUA level <5.0 mg/dL at week 12 compared to the placebo group (2.9%; P-value <0.0001). The mean percentage change in sUA levels from baseline was also significantly greater in the Tigulixostat dose groups (-38.8% to -61.8%) than in the placebo group at all time points (P-value <0.0001). The gout flare rate requiring rescue treatment ranged from 9.4% to 13.2% in the Tigulixostat and placebo groups. The incidence of adverse events was 50.0% to 56.8% by the group, and their severity was mild to moderate. Conclusion: Tigulixostat significantly lowered sUA levels compared to placebo at all doses used with an acceptable safety profile.