Tigulixostat safe at all doses in lowering serum urate levels: CLUE trial

Tigulixostat is safe at all doses, the researchers mentioned.

Researchers evaluated the safety and efficacy of Tigulixostat, a non-purine xanthine oxidase inhibitor, in lowering sUA levels in gout patients with a history of hyperuricemia.

The study was a randomized, double-blind, placebo-controlled, parallel-group, dose-finding phase II trial. Gout patients were randomly assigned to receive daily 50 mg, 100 mg, or 200 mg orally of tigulixostat or placebo for 12 weeks. The primary endpoint is <5.0 mg/dL of serum urate.

The study results could be summarised as follows:

• There was a total of 143 patients.
• Thirty-four patients, 38 patients and 37 patients received 50 mg, 100 mg, and 200 mg tigulixostat, respectively.
• 47.1% in 50 mg, 44.7% in 100 mg, and 62.2% in 200 mg achieved an sUA level of <5.0 mg/dL compared to the placebo at week 12.
• In the placebo group, only 2.9% achieved the range.
• The mean percentage for sUA level change was higher in the tigulixostat dose groups (−38.8% to −61.8%) than in the placebo group.
• In the tigulixostat and placebo groups, the gout flare rate requiring rescue treatment ranged from 9.4% to 13.2%.
• The adverse events incidence was 50.0% to 56.8% by the group with mild to moderate severity.

The researchers said, “This phase II, randomized, double-blind, placebo-controlled trial compared the efficacy of different doses of tigulixostat, a novel xanthine oxidase inhibitor, with that of placebo for reducing serum urate levels in patients with gout and hyperuricemia. A higher proportion of patients treated with tigulixostat achieved a serum urate level below 5.0 mg/dL at 12 weeks (62.2% in the 200-mg group) compared with those who received a placebo (2.9%). Febuxostat was initially included in the study as a comparator group; however, the trial protocol was amended following the FDA black box warning regarding the cardiovascular risk associated with febuxostat use.”

Tigulixostat shows promising results as a novel serum urate–lowering therapy. More extensive studies are needed to better understand its efficacy and safety over a longer-term follow-up.

To conclude, Tigulixostat lowered sUA levels compared to the placebo. The findings are significant at all doses of Tigulixostat, and the safety profile is acceptable.

Further reading:

https://onlinelibrary.wiley.com/doi/10.1002/art.42447