A Multicenter, Randomized, Double-Blind, Parallel Arm, 12-Week Study to Evaluate the Efficacy and Safety of Ezetimibe/Simvastatin Combination Tablet Versus Atorvastatin in Elderly Patients With Hypercholesterolemia at Moderately High Risk and High Risk for CHD

Conditions: Hypercholesterolemia
MedDRA version: 9.1Level: LLTClassification code 10020604Term: Hypercholesterolemia

Registration Number: EUCTR2007-004448-60-FI

Lead Sponsor: MSD Finland Oy

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 1293

Inclusion Criteria

•Patient is a male or post menopausal female and =65 years of age on the day of signing informed consent.
•Patient meets one of the following criteria:
oTherapy naïve patients who are at high risk for CHD with established coronary and other atherosclerotic vascular disease or,
Note: Established atherosclerotic vascular disease includes history of myocardial infarction, stable angina, coronary artery procedures (angioplasty or bypass surgery) or evidence of clinically significant myocardial ischemia. Other atherosclerotic vascular disease includes clinical manifestations of noncoronary forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and carotid artery disease [transient ischemic attacks or stroke of carotid origin or >50% obstruction of a carotid artery]).
Therapy naïve is defined as not being treated with a lipid lowering agent within 6 weeks (8 weeks if a fibrate) prior to Visit 2 (Week -1).
oTherapy naïve patients who are at high risk for CHD without atherosclerotic vascular disease who have diabetes or,
oTherapy naïve patients who are at high risk for CHD without atherosclerotic vascular disease or diabetes with =2 risk factors and a 10-year risk for CHD >20% (as determined by the Framingham calculation) or,
oTherapy naïve patients, or patients rendered naïve by the appropriate prior washout, who are at moderately high risk for CHD with =2 risk factors and a 10-year risk for CHD 10-20% (as determined by the Framingham calculation).
Note: Patients rendered naïve is defined as washed out of a lipid lowering agent for 6 weeks (8 weeks if a fibrate) prior to Visit 2 (Week -1).
•Patient has a baseline LDL-C level of =130 mg/dL at Visit 2 (Week -1).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

•Patient has a hypersensitivity or intolerance to ezetimibe, simvastatin or atorvastatin or any component of these medications.
•Patient has exclusionary laboratory values at Visit 1 (Week -3) for either test listed in the table below:
Laboratory TestExclusionary Value
liver transaminases (alanine aminotransferase [ALT] and aspartate aminotransferase [AST])> 1.5 X ULN with no active liver disease
Creatine kinase (CK)> 2 X ULN

•Patient’s triglycerides (TG) are > 350 mg/dL (3.96 mmol/L) at Visit 2.
•Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia, such as hypothyroidism or hyperthyroidism).
Note: A patient with hyper or hypothyroidism is defined by a TSH below the central laboratory's lower limit of the normal reference range or > 20% above the upper limit of the normal reference range. For patients receiving thyroid hormone, there is no lower TSH threshold for entry and the patient must be on a stable dose for > or equal to 6 weeks before the randomization visit. For patients whose TSH is above the entry criteria, thyroid hormone therapy may be adjusted or initiated provided there is time to stabilize the patient and still meet the enrollment timelines. One redraw will be allowed if the original TSH value is less than 40% above or below the reference range, but the patient must meet the criterion upon redraw.
•Patient has congestive heart failure defined by NYHA (New York Heart Association) Class III or IV.
•Patient has unstable angina pectoris.
•Patient has had a myocardial infarction, coronary artery bypass surgery, angioplasty or uncontrolled or severe peripheral artery disease within 3 months of Visit 1 (Week -3).
•Patient has had a partial ileal bypass, gastric bypass, or other significant intestinal malabsorption.
•Patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mm Hg or diastolic >100 mm Hg at Visit 1 (Week -3). Investigators are encouraged to maximize blood pressure control according to current guidelines prior to randomization.
•Patient has impaired renal function (creatinine =2.0 mg/d [176.8 mmol/L]) or a history of nephrotic range proteinuria at Visit 1 (Week -3).
•Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (i.e., secondary causes of hyperlipidemia), such as Cushing syndrome at Visit 1 (Week -3).
•Patient has type 2 diabetes mellitus that is poorly controlled (HbA1c =8.5% at Visit 1 (Week -3) or newly diagnosed (within 3 months of Visit 1) and/or patient has recent history of repeated hypoglycemia or unstable glycemic control.
•Patient has disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
•Patient is known to be HIV positive.
•Patient has a history of malignancy = 5 years prior to signing informed consent, except for adequately treated basal or squamous cell skin cancer or in situ cervical cancer.
•Patient is currently taking cyclosporine, erythromycin, azole antifungals (i.e., itraconazole, ketoconazole, fluconazole) or fusidic acid.