Study of INT-747 as Monotherapy in Participants With Primary Biliary Cirrhosis (PBC)
Condition: Liver Cirrhosis, Biliary
MeSH terms: Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis
Intervention: Placebo; Obeticholic Acid (OCA)
Intervention description: Matching placebo tablets were administered orally once daily.; Starting dose of 10 or 50 mg administered orally once daily, followed by dose titration planned from 10 mg to 25 mg to 50 mg once daily, which could be modified for safety and tolerability issues or to achieve adequate therapeutic response.
Intervention MeSH terms: Chenodeoxycholic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      The primary hypothesis was that obeticholic acid (OCA) will cause a reduction in alkaline
      phosphatase levels in PBC participants, over a 12-week treatment period, as compared to
      placebo.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female participants must be postmenopausal, surgically sterile, or if premenopausal,
             be prepared to use 1 effective method of contraception with all sexual partners during
             the study and for 14 days after the end of dosing.

          -  Male participants must be prepared to use 1 effective method of contraception with all
             sexual partners during the study during the study unless they had a prior vasectomy.

          -  Proven or likely PBC, as demonstrated by the participant presenting with at least 2 of
             the following 3 diagnostic factors:

          -  History of increased alkaline phosphatase (ALP) levels for at least 6 months;

          -  Positive antimitochondrial antibody titer (>1:40 titer on immunofluorescence or M2
             positive by enzyme-linked immunosorbent assay) or PBC-specific antinuclear antibodies
             (antinuclear dot and nuclear rim positive);

          -  Liver biopsy consistent with PBC

          -  Screening ALP level between 1.5 and 10 × upper limit of normal (ULN).

        Exclusion Criteria:

          -  Administration of the following drugs at any time during the 3 months prior to
             screening for the study: ursodeoxycholic acid, colchicine, methotrexate, azathioprine,
             or systemic corticosteroids.

          -  Screening conjugated (direct) bilirubin >2 × ULN.

          -  Screening alanine aminotransferase or aspartate aminotransferase >5 × ULN.

          -  Screening serum creatinine >133 micromoles/liter (1.5 mg/deciliter).

        History or presence of hepatic decompensation (for example, variceal bleeds,
        encephalopathy, or poorly controlled ascites).

          -  History or presence of other concomitant liver diseases including hepatitis due to
             hepatitis B or C virus infection, primary sclerosing cholangitis, alcoholic liver
             disease, definite autoimmune liver disease or biopsy proven nonalcoholic
             steatohepatitis.

          -  Pregnancy.