Effects of Ezetimibe on the Absorption of Oxidized Cholesterol

• Status: Completed
• Trial end date: 2008-09-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Children's Hospital & Research Center Oakland; UCSF Benioff Children's Hospital Oakland
• Collaborator: Merck Schering-Plough
• Treatments: Ezetimibe

Criteria

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