effects of vytorin versus placebo in subjects with primary hypercholesterolemia (study p04420)

Conditions: Hypercholesterolemia

Summary: this is a multicenter, randomized, double-blind, placebo-controlled, parallel-group phase 3 study of vytorin 10/10 (ezetimibe 10 mg with simvastatin 10 mg), vytorin 10/20 (ezetimibe 10 mg with simvastatin 20 mg), and vytorin 10/40 (ezetimibe 10 mg with simvastatin 40 mg) compared to placebo administered daily for 8 consecutive weeks in subjects with primary hypercholesterolemia (ldl-c \>3.64 mmol/l \[140 mg/dl\]). the efficacy of daily vytorin versus placebo in reducing the concentration of ldl-c will be evaluated, and the efficacy of daily vytorin versus placebo with respect to change in the concentrations of total cholesterol, triglycerides, and hdl-c will be compared. the safety of vytorin versus placebo will also be assessed.


Eligibility criteria:
inclusion criteria: * subjects must be \>=18 years and \<=75 years of age, male or female. * primary hypercholesterolemic subject with a plasma ldl cholesterol concentration \>3.64 mmol/l (140 mg/dl) to \ 5.2 mmol/l (200 mg/dl) to \<12.7 mmol/l (500 mg/dl) and triglyceride concentrations of \<=3.99 mmol/l (350 mg/dl) should be met at the same time. at the time of recruitment (visit 1), these values may be lower if the subject is on lipid-lowering therapy. (ie, prior to the start of lipid lowering drug washout) or may be higher at the start of dietary therapy. * liver transaminases (alt, ast) \<=50% above the upper limit of normal, with no active liver disease and ck \<=50% above the upper limit of normal. * clinical laboratory tests (complete blood count \[cbc\], blood chemistries, urinalysis) must be within normal limits, or clinically acceptable to the investigator/sponsor. * women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control. * subjects must be free of any clinically significant diseases other than hyperlipidemia that would interfere with study evaluations. * subjects must understand and be able to adhere to the dosing and visit schedules. * subject must agree to remain on a cholesterol-lowering diet for the duration of the study (according to china adult treatment panel of high blood cholesterol). exclusion criteria: * subjects whose body mass index (bmi=weight \[kg\]/height2 \[m\]) is \>=30 kg/m2 at visit 3 (baseline visit). * subjects who have known hypersensitivity to hmg coa reductase inhibitors. * subjects who consume \>14 alcoholic drinks per week. (a drink is: a can of beer, glass of wine, or single measure of spirits). * any condition or situation, which in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study. * women who are pregnant or nursing. * subjects who have not observed the designated washout periods for any of the prohibited medications. * congestive heart failure defined by nyha as class iii or iv. * uncontrolled cardiac arrhythmia. * myocardial infarction, coronary bypass surgery, or angioplasty within 6 months of study entry. * unstable or severe peripheral artery disease within 3 months of study entry. * unstable angina pectoris within 6 months of study entry. * uncontrolled hypertension (treated or untreated) with systolic blood pressure \>160 mm hg or diastolic \>100 mm hg at study entry. * uncontrolled (as determined by fasting glucose \>180 mg/ml or hba1c \>9%) or newly diagnosed (within 1 month of study entry) diabetes mellitus. * uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, ie, secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone \[tsh\] above upper limit of normal). subjects with a history of hypothyroidism who are on a stable therapy of thyroid hormone replacement for at least 6 weeks are eligible for enrollment if tsh levels are within normal limits before enrollment. * known impaired renal function (plasma creatinine \>2.0 mg/dl), or nephrotic syndrome at study entry. * disorders of the hematologic, digestive, or central nervous systems, including cerebrovascular disease and degenerative disease that would limit study evaluation or participation. * known hiv positive. * cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas). * history of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy. * female subject receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives.