| Eligibility |
Inclusion Criteria:
- Subject must have diabetes mellitus type 2 (fasting plasma glucose >7 mmol/L [126
mg/dL]) of at least 12 months duration at Visit 3 and must be adequately controlled
(glycated hemoglobin [HbA1c] <=9.0%). Subjects must not have had a change in
antidiabetic pharmacotherapy [i.e. changes in dosage (with the exception of +/- 10
units of insulin) or addition of new medication] or experience recent history of
repeated hypoglycemia or unstable glycemic control within 3 months of Visit (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 transluminal coronary intervention (PCTI) 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 have a low-density lipoprotein cholesterol (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 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 and by history has taken 80%
of daily evening doses for the 6 weeks prior to Visit 3 (Baseline Visit).
- Subject must be >=18 years and <=75 years of age.
- Subjects must have maintained a cholesterol lowering diet and exercise program for at
least 4 weeks prior to Screening (Visit 2) and be willing to continue the same diet
and exercise program during the study.
- 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 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 diabetes
mellitus 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
- Subjects must demonstrate their willingness to participate in the study and comply
with its procedures by signing a written informed consent.
Exclusion Criteria:
- Subjects whose body mass index (BMI = weight[kg]/height[m]**2) 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.
- 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).
- 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.
- Subjects who have not observed the designated wash-out period for any of the
prohibited medications.
- 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 lest 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.
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