Tigulixostat (IBI128) vs Febuxostat in Gout

Exclusion Criteria

• •Participants who meet any of the following criteria will be excluded from the study:
• •1. History of allergy or intolerance to any component of febuxostat or Tigulixostat, or previous evidence of poor response to febuxostat treatment (e.g., sUA \> 420 μmol/L after ≥ 6 weeks of febuxostat ≥ 40 mg).
• •2. Acute gout attack within 4 weeks prior to screening or from screening to first dose.
• •3. Use of uric acid-lowering drugs (e.g., allopurinol, febuxostat, probenecid, benzbromarone, dotinurad, recombinant uricase; excluding sodium bicarbonate) within 2 weeks before screening.
• •4. Hyperuricemia caused by secondary gout (e.g., myeloproliferative disease, tumor, organ transplantation, enzyme deficiency, renal tubular dysfunction, lead poisoning, psoriasis, medications), excluding hyperuricemia due to renal insufficiency.
• •5. Use of the following medications or therapies prior to screening or planned during the study:
• •(1)Prior urate oxidase treatment; (2)Concomitant medications affecting uric acid levels within 4 weeks before screening with dose adjustments (e.g., losartan, calcium channel blockers, diuretics, fenofibrate, atorvastatin, α-glucosidase inhibitors, insulin sensitizers, DPP4 inhibitors, SGLT2 inhibitors, metformin, GLP-1 receptor agonists, pyrazinamide, aspirin); (3)Long-term drugs dependent on xanthine oxidase metabolism (e.g., azathioprine, mercaptopurine); (4)Oral corticosteroids ≥ 10 consecutive days, or intramuscular/intravenous/intra-articular corticosteroid injection within 4 weeks before screening; (5)Biologics (e.g., TNF-α inhibitors, IL-1 inhibitors, IL-6 inhibitors) within 12 weeks before screening.
• •6\. History or evidence of any of the following diseases:
• •1. Xanthinuria, Lech-Nyhan syndrome, 5-phosphoribosyl-1-pyrophosphate synthetase superactivity, congenital myogenic hyperuricemia, rhabdomyolysis;
• •2. Uncontrolled severe pain not caused by gout;
• •3. Cardiovascular events or conditions within 6 months (e.g., acute MI, ACS, unstable angina, CABG, PCI, TIA, cerebrovascular accident, severe arrhythmia, NYHA class III/IV heart failure);
• •4. QTcF ≥ 480 ms or history of prolonged QTc interval;
• •5. Poorly controlled hypertension (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg) or recent adjustment of antihypertensive drugs;
• •6. Poorly controlled diabetes (HbA1c ≥ 9.0%);
• •7. Autoimmune or inflammatory diseases requiring systemic immunosuppressive treatment;
• •8. Active peptic ulcer or GI bleeding within 1 month;
• •9. Diseases affecting drug absorption (e.g., IBS, IBD);
• •10. Active hepatitis B, C, HIV, or syphilis infection;
• •11. Active or untreated malignancy within 5 years, except specified low-risk cancers;
• •12. Thyroid dysfunction requiring treatment. 7. Laboratory abnormalities:
• •(1)total bilirubin \> 2×ULN, ALT or AST \> 3×ULN; (2)eGFR \< 30 mL/min/1.73 m². 8. Pregnant or lactating women, or participants unwilling to use effective contraception during the study and for 8 weeks after study end.
• •9\. History of alcohol or drug abuse (weekly alcohol \> 21 units for males, \> 14 units for females).
• •10\. Blood donation or loss ≥ 400 mL within 3 months, or prior blood transfusion.
• •11\. Participation in another interventional clinical trial within 3 months or 5 half-lives of prior investigational drug.
• •12\. Major surgery within 3 months, incomplete recovery, or planned major surgery during study.
• •13\. Presence of mental illness deemed inappropriate for study participation by the investigator.
• •14\. Any other condition judged by the investigator to potentially affect study efficacy or safety evaluation.