Phase 2 Study on Effects of Obeticholic Acid (OCA) on Lipoprotein Metabolism in Participants With Primary Biliary Cirrhosis

This was a phase 2, open-label, multicenter study evaluating the effects of OCA on lipoprotein metabolism in participants with PBC; in particular, OCA's effects on high-density lipoprotein cholesterol. Nuclear magnetic resonance spectroscopy was utilized to quantify the changes in lipoprotein particle sizes and concentrations. Components of reverse cholesterol transport were also assessed.

Key Inclusion Criteria:

• 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
• 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).
• 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.
• Must have provided written informed consent and agreed to comply with the trial protocol.

Key Exclusion Criteria:

• Participants with decompensated PBC (as determined by the Investigator).
• Severe pruritus or systemic treatment for pruritus (for example, treatment with bile acid sequestrants or rifampicin) within 2 months of Day 0.
• 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.

• Uncontrolled diabetes or other uncontrolled or unstable medical condition that may have interfered with trial results.
• 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
• Planned change in diet or exercise habits during participation in the trial.
• Presence or history of clinically significant cardiac arrhythmias that may have prohibited the participant from participating in the trial.
• If female: known pregnancy, or had a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating.
• 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.