Effect of Ezetimibe Plus Simvastatin on Flow-Mediated Brachial Artery Vasoactivity in Subjects With Primary Hypercholesterolemia (Study P03336)

This is an interventional basic science trial for Hypercholesterolemia Read More

Inclusion Criteria:

• Adults (18 years old and older) with primary hypercholesterolemia with a plasma LDL-C >=145 mg/dL and <=250 mg/dL, and plasma TG <=350 mg/dL after adequate drug washout.
• Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable hormone replacement therapy (HRT) or raloxifene regimen for at least 6 weeks prior to study entry and throughout the study period.
• All subjects must agree to refrain from drinking alcohol or caffeine containing beverages for 12 hours prior to each study visit at which a BART assessment is performed; be minimally active (eg, avoid excessive physical activity) for 12 hours prior to each study visit at which a BART assessment is performed; and be willing to observe the NCEP Step I diet, participate in the study, and complete all study-related procedures.

Exclusion Criteria:

• Pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study
• Smoking, excessive alcohol consumption, underlying disease likely to limit life span to less than one year, or known hypersensitivity or any contraindication to simvastatin, ezetimibe, or nitroglycerin
• Existing hypercholesterolemia for which withholding approved lipid-lowering therapy for the duration of the study would be inappropriate
• The following concomitant illnesses: congestive heart failure NYHA Class III or IV; obstructive cardiomyopathy; uncontrolled cardiac arrhythmias; severe aortic stenosis; upper severe aortic stenosis; MI, CABG, or angioplasty within 6 months of study entry; uncontrolled hypertension; unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation; uncontrolled or newly diagnosed (within one month of study entry) diabetes mellitus; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for enrollment); known impairment of renal function (plasma creatinine >2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram); hepatobiliary or hepatic disease (subjects with AST or ALT >2 times the upper limit of reference range will be excluded); HIV positive; and known coagulopathy.
• Use of certain drugs, foods, or other agents known to alter lipid levels or to cause interactions with either ezetimibe or simvastatin