Effects of Ezetimibe on the Absorption of Oxidized Cholesterol

This is an interventional basic science trial for Hypercholesterolemia focused on measuring Hypercholesterolemia, Oxysterol, Ezetimibe, Zetia Read More

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