| Eligibility |
Inclusion Criteria:
- Subjects must demonstrate their willingness to participate in the study and comply
with its procedures by signing a written informed consent.
- 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) using the Friedewald calculation available at the time of randomization
(Baseline Visit).
- Subjects must have triglyceride concentrations of <3.99 mmol/L (350 mg/dL) at Visit 3
(Baseline Visit).
- 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 (primarily percutaneous coronary
transluminal angioplasty (PCTA) with or without stent placement)
- Symptomatic peripheral vascular disease (claudication)
- Documented history of unstable angina or non-Q wave myocardial infarction.
- Subject must be currently taking atorvastatin 10 mg daily and by history has taken 80%
of daily doses for the preceding 6 weeks prior to Visit 3 (Baseline Visit).
- Subjects must have liver transaminases (alanine aminotransferase (ALT), aspartate
aminotransferase (AST) <50% above the upper limit of normal, with no active liver
disease, and creatinine kinase (CK) <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 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 current cholesterol-lowering diet and their current
exercise regimen for the duration of the study.
Exclusion Criteria:
- Subjects whose body mass index (BMI=weight [kg]/height2[m]) is >=30 kg/m2 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.
- Subjects who have not observed the designated washout periods for any of the
prohibited medications.
- 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.
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure
>160 mmHg or diastolic >100 mmHg 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 (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
thyroid-stimulating hormone (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.
- Subjects who are on any of the following concomitant medications:
- Medications that are potent inhibitors of CYP3A4, including cyclosporine,
systemic itraconazole, fluconazole, and ketoconazole, erythromycin or
clarithromycin, nefazodone, mibefradil, protease inhibitors and large amounts of
grapefruit juice (>1 quart/day).
- Lipid-lowering agent: niacin (>200 mg/day) and resins taken within 5 weeks,
fibric acid derivatives taken within 8 weeks, and probucol taken within one year
prior to Visit 3 (Baseline Visit).
- Over the counter lipid lowering agents such as fish oils, garlic and cholestin
taken within 5 weeks prior to Visit 3 (Baseline Visit).
- 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 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.
- Subjects who are currently using orlistat or sibutramine.
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