The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
Condition: Hypercholesterolemia; Coronary Disease
MeSH terms: Heart Diseases; Coronary Disease; Coronary Artery Disease; Myocardial Ischemia; Hypercholesterolemia
Intervention: Ezetimibe/Simvastatin 10/20 mg; simvastatin 40 mg
Intervention description: 1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks; 1 tablet containing 40 mg of simvastatin per day for 6 weeks
Intervention MeSH terms: Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 120.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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).