Effect of Heavy Alcohol Consumption on Farnesoid X Receptor (FXR) Signaling

Inclusion Criteria:

- Individuals ≥ 21 to 65 years old

- Able to provide informed consent & negative urine pregnancy test where appropriate

- Healthy controls must have not consumed any alcohol within 3 months prior to the
screening visit

- Heavy alcohol drinking is defined as > 40 grams per day on average in women and > 60
grams per day on average in men for a minimum of 6 months

- Women of child bearing potential should be willing to practice contraception
throughout the treatment period

Exclusion Criteria:

- Active infection as evidenced by positive urine culture, blood culture, or pneumonia

- Serum creatinine > 1.5 mg/dL

- Known co-existing infection with hepatitis C, hepatitis B, or HIV

- Significant systemic or major illness including COPD, CHF and renal failure that in
the opinion of the Investigator would preclude the patient from participating in and
completing the study.

- Participation in another investigational drug, biologic, or medical device trial
within 30 days prior to Screening

- Previous history of jaundice or signs of liver diseases such as spider angiomata,
ascites, or history of esophageal varices or hepatic encephalopathy

- Total bilirubin > 2 mg/dl and INR > 1.5 Page 20 of 37

- Women who are pregnant or nursing

- Presence of any other disease or condition that is interfering with the absorption,
distribution, metabolism, or excretion of drugs including bile salt metabolism in the
intestine. Patients who have undergone gastric bypass procedures will be excluded
(gastric lap band is acceptable).

- Subjects who are taking warfarin