A Dose Escalation Study of IG3018 in Subjects With Hyperuricemia With or Without Chronic Kidney Disease

Exclusion Criteria

• •For Part 1 and Part 2:
• •Subjects who meet any of the following criteria will be excluded from the study:
• •1. Prior uricase/recombinant uricase (such as Rasburicase or Pegloticase) therapy within 2 weeks prior to screening or last dose of therapy\< 5 times the half-life (whichever is longer).
• •2. Subjects who have acute gout flares requiring treatment within 4 weeks prior to or during screening.
• •3. Major surgery within 3 months prior to the first administration.
• •4. History of malignant tumors within 6 months prior to screening.
• •5. Subjects within the last 3 months have: myocardial infarction, angina, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, cerebral infarction, cerebral hemorrhage, subarachnoid hemorrhage, or transient ischemia attack.
• •6. Subjects who are on other urate-lowering medication (allopurinol, febuxostat, probenecid and benzbromarone) and cannot stop during the study periods included in the run-in phase.
• •7. Subject with underlying medical conditions requiring changes or introduction of drugs that have the potential impact on the serum uric acid levels (e.g., salicylic acids, diuretics, angiotensin receptor blockers, etc.) within at least 1 month prior the screening phase.
• •8. History of gastrointestinal (GI) surgery, including gastric sleeve, colostomy/enterostomy, Roux-en-Y or gastric banding (unless gastric band removed for a minimum of 12 months prior to screening.
• •9. History of GI diseases, including gastrointestinal bleeding moderate to severe gastrointestinal dysfunction, moderate to severe chronic constipation for a minimum of 3 months prior to screening, or newly diagnosed peptic or duodenal ulcer diseases within 4 weeks prior to screening.
• •10. Chronic use of parenteral nutrition including manganese within 3 months prior to screening.
• •11. Subjects who have the history of manganese toxicity or excessive exposure to manganese (i.e., having worked in a mine, foundry, smelter, dry cell battery manufacturing facility) within 2 months prior to screening.
• •12. Inability to swallow oral medications.
• •13. Received treatment with or exposure to an investigational drug or device within 30 days of signing informed consent.
• •14. Subjects with one of positive results of HIV virus or syphilis, or positive hepatitis B virus surface antigen (HBsAg) and the number of copies of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) at screening, or HBsAg (-), hepatitis B core antibody (HBcAb) (+) and the number of copies of HBV DNA ≥ 500 IU/mL (or 2500 copies, or the lower limit of the positive detection value of the study site) after treatment of HBV infection, or positive hepatitis C antibody (HCV-Ab), and hepatitis C virus (HCV) ribonucleic acid (RNA) ≥upper limit of normal (ULN) of the study site during screening phase.
• •15. History of alcohol abuse, or subjects who consumed alcohol within 48 h before the first administration or did not agree to stop using alcohol products during the study.
• •16. Subjects who have previously been diagnosed with the following diseases and have not been able to control them after medication therapy or other treatment. Uncontrolled is defined as hypertension: sSBP ≥ 180 mmHg and/or sDBP ≥ 110 mmHg; or Diabetes mellitus: HbA1c ≥ 9% at screening.
• •17. Subjects with secondary hyperuricemia caused by tumor, hematological system diseases, drugs, etc. except for chronic kidney disease; or hereditary hyperuricemia at screening.
• •18. Subjects undergone kidney transplantation or planning to undergo kidney transplantation at screening.
• •19. Subjects with abnormal biliary function, biliary obstruction, or biliary gallstone at screening; Subjects with alanine aminotransferase (ALT) ≥3 ULN, aspartate aminotransferase (AST)≥3 ULN, or total bilirubin (TBIL) ≥1.5 ULN at screening.
• •20. Prior or current cholestatic liver disease defined as a clinical condition associated with decrease in bile flow due to impaired secretion by hepatocytes or to obstruction of bile flow through intra-or extrahepatic bile ducts.
• •21. History of serious hypersensitivity reaction to a known ingredient of IG3018 tablet judged by the investigator.
• •22. Subjects who are considered unsuitable for participating in the study in the opinion of the investigator judgment.