This is a randomized, open-labeled, parallel group comparison study. Following a 1-week
screening period, patients will be randomized to 1 of 2 treatment groups: ezetimibe/statin
(ezetimibe plus simvastatin, atorvastatin or pravastatin at doses of 10/20, 10/10 or 10/20
mg), or doubling the dose of on-going statin (simvastatin 40 mg, atorvastatin 20 mg, or
pravastatin 40 mg) alone. Study drug will be administered once daily in the evening for 8
weeks. Patients will be instructed to follow an NCEP or similar cholesterol-lowering dietary
regimen throughout the study.
Inclusion Criteria:
80-120 patients will be recruited in this study. All patients meeting the following
criteria and following an NCEP or similar cholesterol-lowering dietary regimen throughout
the study:
- Men or women ≧18 and ≦80 years of age (If female patients receiving hormone therapy
(including hormone replacement therapy, and estrogen antagonist/agonist, or oral
contraceptives) and maintained on a stable dose and regimen for at least 8 weeks prior
to visit 1 and if willing to continue the same regimen throughout the study. Female of
childbearing potential must be using a medically acceptable method of birth
control.).
- Willing to follow an NCEP Therapeutic Lifestyle Changes (TLC) or similar
cholesterol-lowering diet for the duration of the study.
- Patient with hypercholesterolemia who can not achieve the optimal therapeutic goal
with previous statin treatment (simvastatin 20 mg, atorvastatin 10 mg or pravastatin
20 mg alone for at least 12 weeks) will be enrolled into study. The treatment goal in
primary prevention is LDL-C ＜160mg/dL or LDL-C ＜130mg/dL patient with ≧2 risk factors
(risk factors: hypertension, male >=45 years old, family of premature CAD, female
>=55 years old or menopause without hormone replace therapy, smoking); LDL-c ≤ 100
mg/dL in CAD patients (documented by coronary angiogram, positive treadmill test or
thallium scan ),or DM patients (AC>126mg/dL, PC > 200mg/dL, WHO criteria), ischemic
stroke (Neurological dysfunction with documented diagnosis with CT or MRI), peripheral
artery disease.
- Triglyceride (TG) concentrations ≦ 400 mg/dL.
- Liver transaminases (ALT, AST) ≦ 2 x ULN with no active liver disease and CK≦2 x ULN
at screen visit.
Exclusion Criteria:
The following conditions preclude patients from entry into this study:
- Women who are pregnant or lactating.
- History of mental instability, drug/alcohol abuse within the past 5 years, or major
psychiatric illness not adequately controlled and stable on pharmacotherapy
- Patients who have been treated with any other investigational drug within 3 months of
visit 1.
- Patients previously randomized to a study with ezetimibe.
- Active liver disease or Impaired liver function tests (ALT, AST > 2xULN).
- Impaired renal function ( serum creatinine≧1. 5 mg/dL) or nephrotic syndrome at visit
1
- Unstable angina
- Acute Myocardial infarction, coronary bypass surgery within the previous six months of
visit 1.
- Uncontrolled cardiac arrhythmias
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160
mmHg or diastolic > 100 mmHg at visit 1.
- Poorly controlled diabetes mellitus patient (Patients who are under insulin injection
and HbA1c>10. 0%). If the patient treated with MD, no DM medication will be changed
during the study period)
- Uncontrolled endocrine or metabolic disease known to influence serum lipids or
lipoprotein, e. g. hypothyroidism (TSH > 5. 5 uIU/mL). However, patients who are on a
stable therapy of thyroid replacement therapy for at least 6 weeks are eligible for
enrollment.
- Patients hypersensitive to HMG-CoA reductase inhibitors or ezetimibe.
- Patient who is unable to give informed consent (the patient with a legal
representative to sign the informed consent is eligible to participate the study.)
- Any condition or situation which, in the opinion of the investigator, might pose a
risk to the patient or confound the results of the study.
- Prohibited Concomitant Therapies
- Medications that are potent inhibitors of CYP3A4, including cyclosporine,
systemic itraconazole or ketoconazole, erythromycin or clarithromycin,
nefazodone, verapamil and HIV protease inhibitors.
- Lipid-lowering agents including fish oils, Cholestin, bile-acid sequestrants, and
niacin (<200 mg/day) taken within 6 weeks and fibrates taken within 8 weeks prior
to enrollment.
- Oral corticosteroids unless used as replacement therapy for pituitary/adrenal
disease and treated with a stable regimen for at least 6 weeks prior to
enrollment.
- Treatment with psylium, other fiber-based laxatives, and/ or OTC therapies known
to affect serum lipid levels, phytosterol margarines, unless treated with a
stable regimen for at least 6 weeks prior to enrollment, and patient agrees to
remain on constant regimen for the duration of the study.
- Patient is consuming > 250 ml of grapefruit juice per day.
