AEGR-733 and Atorvastatin 20 mg vs. Monotherapy in Moderate Hypercholesterolemia

Recent studies suggest more intensive cholesterol lowering treatment for people at very high
risk of a heart attack, specifically for patients who have heart disease plus major risk
factors. Available medications used alone at even the highest approved doses are not expected
to reach these new target recommendations for cholesterol in a large number of subjects.
Thus, the development of new medications that can provide additional cholesterol lowering may
be beneficial.

This study tests the effectiveness of different doses of the study drug, AEGR-733 alone and
in combination with the approved cholesterol lowering drug, atorvastatin (Lipitor), on
cholesterol. Volunteers will be randomized to one of 6 different study treatments and will
take the assigned medication (3 capsules daily) for 8 weeks.

Inclusion Criteria:

1. Men and women between the ages of 18 and 70 years.

2. Elevated LDL cholesterol based on risk factors for cardiovascular disease or presence
of cardiovascular disease

Exclusion Criteria:

1. Women who are pregnant, lactating, planning to become pregnant, or women of
childbearing potential who have not successfully been using acceptable contraceptive
methods over the previous 3 months, e.g., intrauterine device (IUD) and barrier method
plus spermicide.

2. Uncontrolled hypertension

3. History of chronic kidney problems

4. History of liver disease

5. Positive for Hepatitis B or Hepatitis C.

6. Any major surgical procedure occurring less than 3 months ago

7. Cardiac insufficiency

8. History of a malignant cancer (other than basal cell or squamous cell carcinoma of the
skin that has been removed) within the previous 5 years.

9. Regular alcohol use >1 drink per day.

10. Regular consumers of grapefruit juice, or currently taking the following medications:
cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, telithromycin,
HIV protease inhibitors, and nefazodone.

11. Use of other cholesterol lowering medications that cannot be stopped.

12. Heart attack or stroke within the previous 6 months

13. Diabetes Mellitus

14. Body mass index (BMI) ≥ 40 kg/m2.

15. Significant gastrointestinal symptoms, such as irritable bowel syndrome.

16. Current use of fish oils, niacin, and herbal weight loss products that cannot be
stopped.