Effects of Ezetimibe on the Absorption of Oxidized Cholesterol
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: ezetimibe; placebo
Intervention description: Blinded study medication (ezetimibe 10 mg in tablet form) will be taken orally once daily in the morning on rising. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.; Blinded study medication (matched placebo) will be taken orally once daily in the morning on rising. Single-blind ezetimibe placebo will be taken during the Run-In Period. Patients will be issued one bottle containing either active drug or placebo for each treatment period.
Intervention MeSH terms: Ezetimibe
Phase: Phase 4
Study type: Interventional
Primary purpose: Basic Science
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Hypercholesterolemia; Oxysterol; Ezetimibe; Zetia

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.
    

Eligibility 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