Effects of Ezetimibe on the Absorption of Oxidized Cholesterol
Effects of Ezetimibe on the Absorption of Oxidized Cholesterol
The purpose of this study is to test the effects of Zetia™ (ezetimibe) 10 milligrams (mg) on
 the absorption of oxysterol into the blood following a meal containing oxysterol.
There are a number of cholesterol-lowering drugs available that can lower blood cholesterol
 to a healthier level. Zetia™ (ezetimibe) 10 mg is available by prescription for the treatment
 of high cholesterol. While Zetia has been shown to inhibit the absorption of dietary
 cholesterol into the bloodstream, its effects on oxysterol absorption from the diet have not
 been completely evaluated.
Inclusion Criteria:

 -  Not currently pregnant or lactating and is highly unlikely to conceive

 -  Body Mass Index (BMI) between 20-30 kilograms per meter squared (kg/m2) inclusive.

 -  Body weight, as reported by patient, stable (±2 kg) for >6 weeks

 -  Plasma low density lipoprotein cholesterol (LDL-C) between 130 and 180 milligrams per
 deciliter (mg/dL) inclusive. Note: One retest allowed.

 -  Triglyceride (TG) concentrations ≤150 mg/dL. Note: One retest allowed.

 -  Fasting blood glucose <110 mg/dL and hemoglobin A1c (HbA1C) ≤ 6 percent at Visit 1.
 Note: One retest allowed.

 -  Liver transaminases (ALT, AST) ≤1.5 x upper limit of normal (ULN) and no active liver
 disease. Note: One retest allowed.

 -  Creatine Phosphokinase (CPK) ≤2x ULN. Note: One retest allowed.

 -  Willingness to maintain a stable diet for the duration of the study.

 -  Can understand and comply with study procedures and signs a written informed consent.

 -  Patient is ≥80 precent compliant with dosing during Placebo Run-In Period or, in the
 opinion of the investigator, is able to maintain ≥80 percent therapy compliance during
 the active treatment period of the study.

 Exclusion Criteria:

 -  Lipid-lowering therapy and replacement of this therapy with study medication is
 considered inappropriate by the investigator.

 -  Consumes an average of more than 2 alcoholic drinks per day.

 -  Smokes.

 -  Currently engages in a vigorous exercise regimen or intensive exercise bouts >4x per
 month.

 -  Treated with any other investigational drug within 30 days of Visit 1.

 -  Hypersensitivity or intolerance to ezetimibe or any component of this medication.

 -  Any condition or situation which poses a risk to the patient or interfere with
 participation in the study.

 -  Congestive heart failure.

 -  Uncontrolled cardiac arrhythmias.

 -  History of myocardial infarction, stroke, or any other clinical manifestation of
 coronary, cerebral, or peripheral vascular disease.

 -  Uncontrolled hypertension

 -  Impaired renal function, nephrotic syndrome or other clinically significant renal
 disease at Visit 1.

 -  Active or chronic hepatobiliary or hepatic disease.

 -  History of irritable bowel syndrome, ileal bypass, gastric bypass or any
 gastrointestinal disorder/condition associated with malabsorption.

 -  Uncontrolled endocrine or metabolic disease known to influence serum lipids or
 lipoproteins.

 -  Type I or Type II diabetes mellitus.

 -  Disorders of the hematologic, digestive, or central nervous systems including
 cerebrovascular disease and degenerative disease that would limit study evaluation or
 participation.

 -  Human Immunodeficiency Virus (HIV) positive.

 -  History of cancer within the past 5 years (except for successfully treated basal and
 squamous cell carcinomas).

 -  History of uncontrolled psychiatric illness or drug/alcohol abuse within the past 5
 years. Individuals with psychiatric illness adequately controlled and stable on
 pharmacotherapy may be enrolled at the discretion of the investigator.

 -  Lipid-lowering agents taken within 6 weeks and fibrates taken within 8 weeks prior to
 visit 3.

 -  Cardiovascular medications are acceptable provided the patient has been on a stable
 regimen for at least 6 weeks prior to Visit 3 and indicates a willingness to continue
 the stable regimen for the duration of the study.

 -  Supplementation with antioxidants beyond a standard multivitamin for the duration of
 the study.

 -  Psyllium, other fiber-based laxatives, and/or over the counter (OTC) therapies known
 to affect serum lipid levels taken within 6 weeks of Visit 3.

 -  Female patients receiving hormone replacement therapy, any estrogen antagonist/agonist
 or hormonal contraceptives.

 -  Treatment with cyclosporine except for ophthalmic indication

 -  Anti-obesity medications such as orlistat or sibutramine taken within 3 months prior
 to Visit 1.

 -  Therapeutic doses of systemic corticosteroids except inhaled steroid therapy (for
 example, Pulmicort®) maintained on a stable dosing regimen for at least 6 weeks prior
 to randomization (Visit 3) and throughout the duration of the study