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

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

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, 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 (HMG
CoA) 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 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