Study of INT-747 as Monotherapy in Patients With PBC

Inclusion Criteria:

• Male or female age 18 to 70 years.
• Female patients must be postmenopausal, surgically sterile, or prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of dosing.
• Male patients must be prepared to use 2 methods of contraception with all sexual partners during the study and for 14 days after the end of the dosing.
• Proven or likely PBC, as demonstrated by the patient presenting with at least 2 of the following 3 diagnostic factors:
• History of increased AP levels for at least 6 months prior to Day 0
• Positive AMA titer (>1:40 titer on immunofluorescence or M2 positive by ELISA) or PBC-specific antinuclear antibodies (antinuclear dot and nuclear rim positive)
• Liver biopsy consistent with PBC
• Screening AP value between 1.5 and 10 × ULN

Exclusion Criteria:

• Administration of the following drugs at any time during the 3 months prior to screening for the study: ursodeoxycholic acid (UDCA, URSO®), colchicine, methotrexate, azathioprine, or systemic corticosteroids.
• Screening conjugated (direct) bilirubin >2 × ULN.
• Screening ALT or AST >5 × ULN.
• Screening serum creatinine >133 μmol/L (1.5 mg/dL). History or presence of hepatic decompensation (e.g., variceal bleeds, encephalopathy, or poorly controlled ascites).
• History or presence of other concomitant liver diseases including hepatitis due to hepatitis B or C virus (HCV, HBV) infection, primary sclerosing cholangitis (PSC), alcoholic liver disease, definite autoimmune liver disease or biopsy proven nonalcoholic steatohepatitis (NASH).
• Pregnancy.