Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)
Condition: Hypercholesterolemia
MeSH terms: Hypercholesterolemia
Intervention: ezetimibe with simvastatin; Ezetimibe with Simvastatin; Ezetimibe with Simvastatin; Placebo
Intervention description: Ezetimibe 10 mg with Simvastatin 10 mg once daily for a total of eight weeks; Ezetimibe 10 mg with Simvastatin 20 mg once daily for a total of eight weeks; Ezetimibe 10 mg with Simvastatin 40 mg once daily for a total of eight weeks; Placebo once daily for a total of eight weeks
Intervention MeSH terms: Simvastatin; Ezetimibe
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 392.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3
      study of Vytorin 10/10 (ezetimibe 10 mg with simvastatin 10 mg), Vytorin 10/20 (ezetimibe 10
      mg with simvastatin 20 mg), and Vytorin 10/40 (ezetimibe 10 mg with simvastatin 40 mg)
      compared to placebo administered daily for 8 consecutive weeks in subjects with primary
      hypercholesterolemia (LDL-C >3.64 mmol/L [140 mg/dL]). The efficacy of daily Vytorin versus
      placebo in reducing the concentration of LDL-C will be evaluated, and the efficacy of daily
      Vytorin versus placebo with respect to change in the concentrations of total cholesterol,
      triglycerides, and HDL-C will be compared. The safety of Vytorin versus placebo will also be
      assessed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subjects must be >=18 years and <=75 years of age, male or female.

          -  Primary hypercholesterolemic subject with a plasma LDL cholesterol concentration >3.64
             mmol/L (140 mg/dL) to <=6.3 mmol/L (250 mg/dL) using the Friedewald calculation; total
             cholesterol (TC) >5.2 mmol/L (200 mg/dL) to <12.7 mmol/L (500 mg/dL) and triglyceride
             concentrations of <=3.99 mmol/L (350 mg/dL) should be met at the same time. At the
             time of recruitment (Visit 1), these values may be lower if the subject is on
             lipid-lowering therapy. (ie, prior to the start of lipid lowering drug washout) or may
             be higher at the start of dietary therapy.

          -  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.

          -  Clinical laboratory tests (complete blood count [CBC], blood chemistries, urinalysis)
             must be within normal limits, or clinically acceptable to the investigator/sponsor.

          -  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.

          -  Subjects must be free of any clinically significant diseases other than hyperlipidemia
             that would interfere with study evaluations.

          -  Subjects must understand and be able to adhere to the dosing and visit schedules.

          -  Subject must agree to remain on a cholesterol-lowering diet for the duration of the
             study (according to China Adult Treatment Panel of High Blood Cholesterol).

        Exclusion Criteria:

          -  Subjects whose body mass index (BMI=weight [kg]/height2 [m]) is >=30 kg/m2 at Visit 3
             (Baseline Visit).

          -  Subjects who have known hypersensitivity to HMG CoA reductase inhibitors.

          -  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.

          -  Congestive heart failure defined by NYHA as Class III or IV.

          -  Uncontrolled cardiac arrhythmia.

          -  Myocardial infarction, coronary bypass surgery, or angioplasty within 6 months of
             study entry.

          -  Unstable or severe peripheral artery disease within 3 months of study entry.

          -  Unstable angina pectoris within 6 months of study entry.

          -  Uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mm
             Hg or diastolic >100 mm Hg at study entry.

          -  Uncontrolled (as determined by fasting glucose >180 mg/mL or HbA1c >9%) or newly
             diagnosed (within 1 month of study entry) diabetes mellitus.

          -  Uncontrolled endocrine or metabolic disease known to influence serum lipids or
             lipoproteins, ie, secondary causes of hyperlipidemia, such as secondary
             hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone [TSH] above
             upper limit of normal). 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 before enrollment.

          -  Known impaired renal function (plasma creatinine >2.0 mg/dL), or nephrotic syndrome at
             study entry.

          -  Disorders of the hematologic, digestive, or central nervous systems, including
             cerebrovascular disease and degenerative disease that would limit study evaluation or
             participation.

          -  Known 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.

          -  Female subject receiving hormonal therapy, including hormone replacement, any estrogen
             antagonist/agonist, or oral contraceptives.