Tigulixostat lowers uric acid levels in gout patients with hyperuricemia: Study
USA: Tigulixostat significantly lowers the levels of serum uric acid (sUA) in gout patients with hyperuricemia versus placebo at all dose levels, according to results from a phase 2, dose-finding study. Also, the sUA lowering effect of tigulixostat appeared to be dose-dependent. Study participants tolerated well to the treatment with tigulixostat at all 3 dose levels.
The study was presented as the late-breaking posters at the ACR (American College of Rheumatology) Convergence 2021.
Gout, a form of arthritis, can be effectively managed by inhibiting uric acid synthesis. Tigulixostat, a novel non-purine selective xanthine oxidase inhibitor, lowers uric acid production and is shown to be well tolerated up to the maximum dose of 800 mg/day for seven-day administration in healthy subjects in a first-in-human clinical study.
Robert Terkeltaub, Professor of Medicine at the University of California, San Diego and Chief of Rheumatology at the VA Medical Center in San Diego, and colleagues conducted this phase 2 study in the US to assess the safety and efficacy of tigulixostat in gout patients with hyperuricemia and to find the appropriate doses for further development.
The study included gout patients with serum uric acid (sUA) ≥8.0 mg/dL to ≤12.0 mg/dL after a wash-out/prophylaxis period. They were randomized to one of tigulixostat 50 mg (n=34), 100 mg (n=38), 200 mg (n=37), or placebo groups (n=34) and received the study treatment, once-daily oral intake, for 12 weeks. The participants took colchicine 0.6 mg once daily as a gout flare prophylaxis from the screening period and until the end of the treatment.
The primary endpoint was the proportion of the subjects achieving sUA < 5 mg/dL at week 12.
Based on the study, the researchers found the following:
- Differences in the proportion to the placebo group were statistically significant at all tigulixostat dose levels at both sUA levels.
- The superiority of tigulixostat groups over the placebo group was demonstrated in the primary endpoint.
- Tigulixostat rapidly lowered sUA within 2 weeks from treatment initiation, and the sUA levels were well maintained throughout the study treatment period.
- Mean of maximum percent reduction in sUA was -46.67%, -50.64% and -66.79% and -11.20, respectively.
- Total 12.9%, 13.16%, 10.81%, and 9.38% of the subjects had gout flares that required rescue treatment, respectively.
- TEAEs were comparable across treatment and placebo groups, and no serious TEAEs were reported during the study period.
- There were three severe TEAEs, and all of them were resolved or resolved with sequelae and were not related to tigulixostat.
"These results and the observed safety profile support dose-finding of tigulixostat and the continued development of tigulixostat in gout patients with hyperuricemia," the authors conclude.
ABSTRACT NUMBER: L05. Phase 2 Study Results from a Randomized, Double-blind, Placebo-controlled, Dose-finding Study to Evaluate Efficacy and Safety of Tigulixostat, a Novel Non-purine Selective Xanthine Oxidase Inhibitor, in Gout Patients with Hyperuricemia