The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
This study is being conducted to compare the efficacy, safety, and tolerability of
 ezetimibe/simvastatin 10/20 mg when administered daily versus doubling the dose of
 simvastatin to 40 mg in patients with hypercholesterolemia and coronary heart disease.
Inclusion Criteria:

 -  Subjects must have documented coronary heart disease (CHD). For the purposes of this
 study, CHD will include one or more of the following features: documented stable
 angina (with evidence of ischemia on exercise testing); history of myocardial
 infarction; history of percutaneous coronary intervention [PCI] (primarily PCI with or
 without stent placement); symptomatic peripheral vascular disease (claudication);
 documented history of atherothrombotic cerebrovascular disease; and/or documented
 history of unstable angina or non-Q wave myocardial infarction.

 -  Subjects must demonstrate their willingness to participate in the study and comply
 with its procedures by signing a written informed consent.

 -  History of myocardial infarction (heart attack).

 -  Subjects must be >= 18 years and <= 75 years of age.

 -  Subjects must have an LDL-C concentration >= 2.6 mmol/L (100 mg/dL) to <= 4.1 mmol/L
 (160 mg/dL) at the time of randomization (Visit 3/Baseline Visit).

 -  Subjects must have triglyceride concentrations of < 3.99 mmol/L (350 mg/dL) at (Visit
 3 Baseline Visit).

 -  Subject must be currently taking simvastatin 20 mg daily.

 -  Subjects must have liver transaminases (ALT [alanine aminotransferase], AST [aspartate
 aminotransferase]) < 50% above the upper limit of normal, with no active liver
 disease, and CK (creatine kinase) < 50% above the upper limit of normal at Visit 3
 (Baseline Visit).

 -  Clinical laboratory tests (complete blood count [CBC], blood chemistries, urinalysis)
 must be within normal limits or clinically acceptable to the investigator at Visit 3
 (Baseline Visit).

 -  Subjects must have maintained a cholesterol-lowering diet and exercise program for at
 least 4 weeks prior to the study and be willing to continue the same diet and exercise
 program during the study.

 -  Subjects must report a stable weight history for at least 4 weeks prior to entry into
 study at Visit 3 (Baseline Visit).

 -  Women receiving hormonal therapy, including hormone replacement, any estrogen
 antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose
 and regimen for at least 8 weeks and be willing to continue the same regimen for the
 duration of the study.

 -  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 (e.g., hormonal contraceptive, medically prescribed
 intrauterine device [IUD], condom in combination with spermicide) or be surgically
 sterilized (e.g., hysterectomy or tubal ligation).

 -  Subjects must be free of any clinically significant diseases other than hyperlipidemia
 or coronary heart disease that would interfere with study evaluations.

 -  Subjects must understand and be able to adhere to the dosing and visit schedules, and
 must agree to remain on their cholesterol-lowering diet and their exercise regimen for
 the duration of the study.

 Exclusion Criteria:

 -  Subjects whose body mass index (BMI = weight [kg]/height2 [m]) is >= 35 kg/m^2 at
 Visit 3 (Baseline Visit).

 -  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.

 Exclusion Criteria: subjects who have the following medical conditions:

 -  Congestive heart failure defined by New York Heart Association (NYHA) as Class III or
 IV.

 -  Uncontrolled cardiac arrhythmia.

 -  Myocardial infarction, acute coronary insufficiency, coronary artery bypass surgery,
 or angioplasty within 3 months of Visit 3 (Baseline Visit).

 -  Unstable or severe peripheral artery disease within 3 months of Visit 3 (Baseline
 Visit).

 -  Newly diagnosed or currently unstable angina pectoris (chest pain).

 -  Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm
 Hg or diastolic > 100 mm Hg at Visit 3 (Baseline Visit).

 -  Type I or Type II diabetes mellitus.

 -  Uncontrolled endocrine or metabolic disease known to influence serum lipids or
 lipoproteins, i.e., secondary causes of hyperlipidemia, such as secondary
 hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone [TSH] above
 upper limit of normal) at Visit 3. 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 at Visit 3 (Baseline Visit).

 -  Impaired renal function (creatinine > 2.0 mg/dL) or nephrotic syndrome at Visit 3
 (Baseline Visit).

 -  Disorders of the hematologic, digestive, or central nervous systems including
 cerebrovascular disease and degenerative disease that would limit study evaluation or
 participation.

 -  Known Human Immunodeficiency Virus (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.

 Exclusion Criteria: subjects who are on any of the following concomitant medications:

 -  Subjects who have not observed the designated wash-out period for any of the
 prohibited medications.

 -  Subjects who have not stopped taking various prohibited medications for a minimum
 period of time before Visit 3, including amiodarone hydrochloride (6 months) and
 probucol (12 months).

 -  Subjects currently consuming large amounts of grapefruit juice (> 1 liter/day).

 -  Oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease
 and the subject is on a stable regimen for at least 6 weeks prior to Visit 3 (Baseline
 Visit).

 -  Subjects who are currently using cardiovascular medication (e.g. antihypertensive,
 antiarrhythmic) and have not been on a stable regimen for at least 6 weeks prior to
 Visit 3 (Baseline Visit) and it is expected to change during the study.

 -  Subjects who are currently using psyllium, other fiber-based laxatives, and/or any
 other over-the-counter (OTC) therapy known to affect serum lipid levels (phytosterol
 margarine), and have not been on a stable regimen for at least 5 weeks prior to study
 entry Visit 3 (Baseline Visit) and who do not agree to remain on this regimen
 throughout the study.

 -  Subject who are currently using orlistat or sibutramine.

 -  Subjects who are currently using amiodarone hydrochloride.

 -  Subjects who are currently using danazol.

 -  Subjects who are currently using coumarin anticoagulants (warfarin).

 -  Subjects who are using (at the Screening Visit / Visit 1) any statin other than
 simvastatin 20 mg, or ezetimibe alone or in combination with any statin (including the
 fixed combination with simvastatin).