BMS Reverse Cholesterol Transport (RCT) Study

The study will use 3H-cholesterol bound to albumin (particulate cholesterol) to assess the
ability of HDL to transport cholesterol to the liver to be eliminated. This process is called
Reverse Cholesterol transport and is one of the main mechanisms by which HDL protect against
atherosclerotic cardiovascular disease. The availability of a method to assess RCT is
important for the development of new drugs which affect RCT and may result in useful
treatments for atherosclerosis.

This study will evaluate the use of radiolabeled particulate cholesterol administered
intravenously in association with albumin, as a method to study reverse cholesterol transport
(RCT) in humans by analyzing changes in the tracer activity in total plasma and lipoproteins.
The study population is healthy volunteers.

Inclusion Criteria:

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

2. Female subjects must be of non-childbearing potential. They must have been surgically
sterilized at least 6 months prior to screening or be postmenopausal. Postmenopausal
women must have no regular menstrual bleeding for at least 2 years prior to inclusion.
.

3. Subjects must be in good overall health

4. Subjects must be able to comprehend and willing to provide a signed IRB approved
Informed Consent Form.

5. Subjects must be willing to comply with all study-related procedures.

Exclusion Criteria:

1. Known cardiovascular disease, including coronary disease, cerebrovascular disease, or
peripheral vascular disease

2. History of diabetes mellitus or fasting glucose > 126 mg/dL at the screening visit

3. History of any other endocrine disease

4. History of a non-skin malignancy within the previous 5 years

5. Anemia; Hemoglobin less than 10 g/dL

6. Renal insufficiency as defined by creatinine ³ 1.3 mg/dl

7. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory
condition

8. History of hypertension

9. Use of warfarin, or any known coagulopathy and /or elevated PT/PTT >1.5 x ULN

10. Self-reported history of HIV positive

11. Previous organ transplantation

12. Clinical evidence of liver disease or liver injury as indicated by abnormal liver
function tests such as ALT or AST > 1x ULN, or self-reported history of positive
Hepatitis B or Hepatitis C test result

13. Any major surgical procedure that occurred within the previous 3 months of the
screening visit

14. Use of tobacco products currently or during the previous 30 days

15. History of drug abuse (< 3 years)

16. Regular use of alcoholic beverages (> 2 drinks/day)

17. Body mass index (BMI) > 30 kg/m2 or < 18.5 kg/m2

18. Participation in an investigational drug study within 6 weeks prior to the screening
visit

19. Serious or unstable medical or psychological conditions that, in the opinion of the
investigator, would compromise the subject's safety or successful participation in the
study will be excluded.

20. Use of lipid lowering drugs within the 6 weeks prior to dosing or during the study

21. Use of other prescription or non-prescription drugs (including vitamins and herbal
supplements, but excluding replacement hormone therapy) within 2 weeks prior to dosing
or during the study, however, acetaminophen up to 2g/day is acceptable.

22. Male subjects who plan to conceive a child within 3 months of the conclusion of the
study.