The study is to evaluate the effectiveness and safety of switching to coadministration ezetimibe and atorvastatin compared with doubling the dose of atorvastatin or switching to rosuvastatin in patients with primary hypercholesterolemia and high cardiovascular risk who are not adequately controlled with atorvastatin 10 mg. Ezetimibe, atorvastatin and rosuvastatin are each available by prescription to treat high blood cholesterol levels.
- Conditions
- Primary HypercholesterolemiaMedDRA version: 14.1 Level: PT Classification code 10020603 Term: Hypercholesterolaemia System Organ Class: 10027433 - Metabolism and nutrition disordersTherapeutic area: Body processes [G] - Metabolic Phenomena [G03]
- Registration Number
- EUCTR2009-015247-16-NL
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 1508
1. Men or women =18 and <80 years of age.
2. Patient understands the study procedures, risks involved with the study, and voluntarily agrees to participate by giving written informed consent.
3. Patient is at high cardiovascular risk (determined by a preliminary Cardiovascular Risk Assessment using historical lab values) and one of the following conditions are met:
- Naïve to lipid-lowering therapy (or have been off such therapy for =6 weeks prior to Visit 1) and has a historical LDL-C value approximately within the range noted in the protocol*
OR
- Currently taking stable dose of a statin, ezetimibe, or statin + ezetimibe combination listed below with LDL-C lowering efficacy equivalent to or less than atorvastatin 10 mg and has a historical LDL-C value approximately within the range noted in the protocol.:*
Simvastatin 10, 20 mg
Pitavastatin 1 mg
Atorvastatin 10 mg
Pravastatin 10, 20, 40 mg
Fluvastatin 20, 40, 80 mg
Lovastatin 10, 20, 40 mg
Ezetimibe 10 mg
Ezetimibe 10 mg + Lovastatin 10 mg
Ezetimibe 10 mg + Pravastatin 10 mg
Ezetimibe 10 mg + Fluvastatin 20 mg
4. Patient is willing to maintain an ESC / NCEP ATP III Therapeutic Lifestyle Changes(TLC) or similar cholesterol lowering diet for the duration of the study.
5. A female patient who is of reproductive potential agrees to remain abstinent or use (or have their partner use) 2 acceptable methods of birth control for the duration of the study. Acceptable methods of birth control are: intrauterine device (IUD), diaphragm with spermicide, condom, vasectomy, and non-cyclical hormonal
contraception.*
6. Female patients who are receiving non-cyclical hormone therapy (including noncyclical hormone replacement therapy or any estrogen antagonist/agonist, or noncyclical oral contraceptives) if 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.
Patients will be eligible to continue to Visit 3 (Week -1) if they meet the following criteria:
7. Patient has a naïve or on-treatment LDL-C value within the range noted in the protocol at Visit 2 (sample collected at Visit 1).
8. Patient has liver transaminases (ALT and AST) =2xULN (sample collected at Visit 1) with no active liver disease at Visit 2.
9. Patient has creatine kinase (CK) levels =3xULN at Visit 2 (sample collected at Visit 1).
10. Patient has triglyceride (TG) concentrations =350 mg/dL (3.95 mmol/L) at Visit 2 (sample collected at Visit 1).
11. Patient meets 2004 NCEP ATP III / 2006 AHA ACC updated guidelines and 2007 Fourth Joint European Societies recommendations for high risk. Risk criteria are determined by the Framingham calculation (using lipid values obtained at Visit 1)*
- High-risk patients without car
1. Patient is Asian.
2. Patient has hypersensitivity or intolerance to ezetimibe, atorvastatin, rosuvastatin, or any component of these medications, or has a history of significant myopathy or rhabdomyolysis with ezetimibe or any statin.
3. Patient routinely consumes more than 2 alcoholic drinks per day (average >14 alcoholic drinks per week). *
4. Female patient who is pregnant or lactating.
5. Patient has been treated with any other investigational drug within 30 days of Visit 1 (Week -6).
6. Patient has any condition or situation which, in the opinion of the investigator, might have posed a risk to the patient or interfere with participation in the study.
Prohibited Medical Conditions
7. Patient has congestive heart failure defined by NYHA (New York Heart Association) Class III or IV.
8. Patient has had a myocardial infarction, coronary artery bypass surgery, angioplasty, or acute coronary syndrome within 3 months prior to Visit 1.
9. Patient has uncontrolled cardiac arrhythmias or recent significant changes in the patient’s electrocardiogram (ECG) as taken within 6 months prior to Visit 1.
10. Patient has homozygous familial hypercholesterolemia or has undergone LDL-C apheresis.
11. Patient has had a partial ileal bypass, gastric bypass, or other significant intestinal malabsorption.
12. Patient has uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic >100 mmHg at Visit 2 (Week –5). Investigators are encouraged to maximize blood pressure control according to current guidelines.
13. Patient has estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 based on the 4-variable MDRD (Modification of Diet in Renal Disease) equation at Visit 1 (as done by the central lab), nephrotic syndrome or other clinically significant renal disease at Visit 1 (Week -6).
14. Patient has uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins at Visit 1 (Week -6).*
15. Patient has disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease (e.g. stroke, TIA) and degenerative disease that would limit study evaluation or participation.
16. Patient has poorly controlled Type I or II diabetes mellitus (HbA1c =8.5% at Visit 1 or newly diagnosed (within 3 months of Visit 1) and/or patient has recent history of repeated hypoglycemia or unstable glycemic control, or has had a change in treatment of antidiabetic pharmacotherapy or change of ±10 units of insulin, within 2 months of Visit 1 (Week -6).*
17. Patient who is known HIV positive.*
18. Patient has a history of malignancy =5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.*
19. Patient has a history of mental instability, drug/al
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method