Ezetimibe Plus Atorvastatin Versus Atorvastatin in Untreated Subjects With Primary Hypercholesterolemia and Coronary Heart Disease (P03396)
Ezetimibe Plus Atorvastatin Versus Atorvastatin in Untreated Subjects With Primary Hypercholesterolemia and Coronary Heart Disease (P03396)
The primary objective is to evaluate the efficacy and safety of coadministration of ezetimibe
 10 mg with atorvastatin 10 mg in untreated subjects with primary hypercholesterolemia and
 coronary heart disease for whom diet and exercise have failed. The primary variable is
 LDL-cholesterol (LDL-C), and the secondary variable is total cholesterol (TC), HDL-C, and
 triglycerides (TG). The following variables were used to assess the safety and compliance of
 the drug: vital signs and laboratory values. Variables were measured before the first
 administration of the drug and at the last administration of the drug, after 6 weeks of
 treatment. Adverse events were also assessed.
Inclusion Criteria:

 Diagnosis and Criteria for Inclusion:

 -  Diagnosis: This study was designed for untreated subjects with primary
 hypercholesterolemia with plasma LDL-C concentrations between >=3.3 mmol/L (130 mg/dL)
 to <=4.6 mmol/L (180 mg/dL) and triglyceride concentrations of <3.99 mmol/L (350
 mg/dL), and coronary heart disease for whom diet and exercise have failed and now
 require drug therapy.

 -  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 >=3.3 mmol/L (130 mg/dL) to <=4.6 mmol/L
 (180 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).

 -  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 PTCA 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 not be currently taking an approved statin. Subjects with a previous
 history of statin use must have not used a statin for at least 6 months prior to Visit
 3 (Baseline Visit).

 -  Subjects must have 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 at
 Visit 3 (Baseline Visit).

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

 -  Subjects must have failed a cholesterol-lowering diet and exercise program of at least
 4 weeks duration prior to 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 became sexually active) must be using an acceptable
 method of birth control (eg, hormonal contraceptive, medically prescribed IUD, condom
 in combination with spermicide) or be surgically sterilized (eg, 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 maintain their current cholesterol-lowering diet and their current
 exercise program for the duration of the study.

 Exclusion Criteria:

 -  Subjects whose body mass index is >=30 kg/sqm at baseline.

 -  Subjects who have known hypersensitivity to HMG-CoA reductase inhibitors.

 -  Subjects who consume >14 alcoholic drinks per week.

 -  Any condition or situation that, 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 designated washout periods for prohibited medications
 (eg, potent inhibitors of CYP3A4, prescription or over-the-counter agents know to
 lower lipid levels, corticosteroids), or have been on a stable regimen of any
 cardiovascular agent for <6 weeks.