Clinical Trial Protocol 747-205 A Phase 2 Clinical Trial Investigating the Effects of Obeticholic Acid on Lipoprotein Metabolism in Subjects with Primary Biliary Cirrhosis

Trial ID:
IRB-14-6336
Paul Pockros
The purpose of this study is to determine if obeticholic acid (OCA) has an effect on cholesterol levels in the blood in patients with PBC.

Inclusion Criteria:

  • 1. Definite or probable primary biliary cirrhosis (PBC) diagnosis as demonstrated by the presence of ≥ 2 of the following 3 diagnostic factors:
    • History of elevated alkaline phosphatase (ALP) 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. Age ≥ 18 years
  • 3. 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)
  • 4. Contraception: Female subjects must be postmenopausal, surgically sterile, or if premenopausal, be 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.
  • 5. Must provide written informed consent and agree to comply with the trial protocol.

Exclusion Criteria:

  • 1. Subjects with decompensated PBC (as determined by the Investigator)
  • 2. Severe pruritus or systemic treatment for pruritus (e.g. 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 (HBV, HCV) infection
    • Primary sclerosing cholangitis (PSC)
    • Alcoholic liver disease
    • Definite autoimmune liver disease or overlap hepatitis
    • Nonalcoholic steatohepatitis (NASH)

    NOTE: Subjects with Gilbert's disease or those with a history of hepatitis B who are currently antigen negative and seroconverted should not be considered exclusionary

  • 4. Uncontrolled diabetes or other uncontrolled or unstable medical condition that may interfere with trial results
  • 5. Administration of any of the following medications as specified below:
    • Prohibited 28 days prior to Day 0: bile acid sequestrants (BAS) including cholestyramine, colesevelam, or colestipol
    • Prohibited 3 months prior to Day 0 and throughout trial participation: serum-lipid modifying agents including 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase inhibitors, fenofibrate or other fibrates, nicotinic acid and derivatives, ezetimibe, Vitamin E (other than as standard dietary supplement), omega-3 fatty acid containing dietary supplements
    • 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 prohibit the subject from participating in the trial
  • 8. If female: known pregnancy, or has 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