Clinical trial NCT00413972: Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Parallel Groups Study Comparing the Efficacy and Safety of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypercholesterolemia
Lead sponsor: Organon and Co
Sponsor class: INDUSTRY
Collaborators: name: Schering-Plough
name: Merck Sharp & Dohme LLC
First posted: 2006-12-20
Enrollment: 392
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint After 8 Weeks of Treatment
timeFrame: Baseline, 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
References: