Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Participants With Primary Biliary Cirrhosis
Condition: Primary Biliary Cirrhosis
MeSH terms: Liver Cirrhosis; Liver Cirrhosis, Biliary; Fibrosis
Intervention: Obeticholic Acid
Intervention description: All participants were treated with OCA (oral administration, 10 mg, once daily [QD]) for 8 weeks and continued their prestudy dose of ursodeoxycholic acid (UDCA). After completion of the 8-week Primary Treatment Phase of the study and the 4-week follow-up period, during which time participants did not take OCA, all eligible participants were offered the opportunity to enter an open-label, long-term safety extension phase, during which they could receive 10 mg OCA QD for up to 2 years.
Intervention MeSH terms: Chenodeoxycholic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Basic Science
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 27.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to determine if OCA had an effect on cholesterol levels in the
      blood in participants with primary biliary cirrhosis (PBC).
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Definite or probable PBC diagnosis as demonstrated by the presence of ≥ 2 of the
             following 3 diagnostic factors:

               -  History of elevated alkaline phosphatase levels for at least 6 months

               -  A positive anti-microbial antibody (AMA) titer or, if AMA negative or in low
                  titer (<1:80), PBC-specific antibodies

               -  Liver biopsy consistent with PBC

          2. Taking UDCA for at least 12 months (stable dose for ≥ 3 months) prior to Day 0 or
             unable to tolerate UDCA (no UDCA for ≥ 3 months prior to Day 0).

          3. Contraception: Female participants must have been postmenopausal, surgically sterile,
             or if premenopausal, were prepared to use ≥ 1 effective (≤ 1% failure rate) method of
             contraception during the trial and until at least 30 days after the last dose of
             Investigational Product.

          4. Must have provided written informed consent and agreed to comply with the trial
             protocol.

        Key Exclusion Criteria:

          1. Participants with decompensated PBC (as determined by the Investigator).

          2. Severe pruritus or systemic treatment for pruritus (for example, treatment with bile
             acid sequestrants or rifampicin) within 2 months of Day 0.

          3. History or presence of other significant liver diseases including:

               -  Active or chronic Hepatitis B or C virus infection

               -  Primary sclerosing cholangitis

               -  Alcoholic liver disease

               -  Definite autoimmune liver disease or overlap hepatitis

               -  Nonalcoholic steatohepatitis

             Note: Participants with Gilbert's disease or those with a history of hepatitis B who
             were currently antigen negative and seroconverted were not considered exclusionary.

          4. Uncontrolled diabetes or other uncontrolled or unstable medical condition that may
             have interfered with trial results.

          5. Administration of any of the following medications as specified below:

               -  Prohibited 28 days prior to Day 0: bile acid sequestrants including
                  cholestyramine, colesevelam, colestipol or omega-3 fatty acid containing dietary
                  supplements

               -  Prohibited 3 months prior to Day 0 and throughout trial participation:
                  serum-lipid modifying agents including 3-hydroxy-3-methylglutaryl-coenzyme A
                  reductase inhibitors, fenofibrate or other fibrates, nicotinic acid and
                  derivatives, ezetimibe, Vitamin E (other than as standard dietary supplement)

               -  Prohibited 6 months prior to Day 0 and throughout the trial participation:
                  azathioprine, colchicine, cyclosporine, methotrexate, mycophenolate mofetil,
                  pentoxifylline; budesonide and other systemic corticosteroids; potentially
                  hepatotoxic drugs (including α-methyl-dopa, sodium valproic acid, isoniazide, or
                  nitrofurantoin)

               -  Prohibited 12 months prior to Day 0 and throughout the trial participation:
                  antibodies or immunotherapy directed against interleukins or other cytokines or
                  chemokines

          6. Planned change in diet or exercise habits during participation in the trial.

          7. Presence or history of clinically significant cardiac arrhythmias that may have
             prohibited the participant from participating in the trial.

          8. If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a
             positive serum pregnancy test), or lactating.

          9. Recent (3 months prior to day 0) participation in another trial involving OCA or
             participation in another investigational trial (30 days prior to Day 0) and during the
             trial.