Ezetimibe Plus Atorvastatin Versus Atorvastatin in Untreated Subjects With High Cholesterol (P03434)

Study Overview
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Brief Summary
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This study was designed to assess whether co-administration of ezetimibe 10 mg with atorvastatin 10 mg in treatment naïve subjects would be more effective than treatment with atorvastatin 10 mg alone for reducing LDL-concentrations.

Official Title
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SCH 58235: A Multicentre, Randomised, Parallel Group, Placebo-Controlled Study Comparing the Efficacy, Safety, And Tolerability of the Daily Co-Administration of Ezetimibe 10 mg With Atorvastatin 10 mg vs. Ezetimibe Placebo With Atorvastatin 10 mg in Untreated Subjects With Primary Hypercholesterolaemia and Coronary Heart Disease

Conditions
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Hypercholesterolemia, Atherosclerosis

Intervention / Treatment
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* Drug: Ezetimibe + Atorvastatin
* Drug: Atorvastatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and non-pregnant female subjects, who demonstrated willingness to participate and comply with procedures by signing informed consent, and who were >=18 years and <=75 years of age, were eligible to participate if they had: a baseline LDL-C concentration >=3.3 mmol/L (130 mg/dL) to <=4.9 mmol/L (190 mg/dL); a baseline triglyceride concentration of <3.99 mmol/L (350 mg/dL); a documented history of coronary heart disease (CHD); a stable weight history for 4 weeks prior to baseline; completion of the designated washout periods for all prohibited medications; and did not fulfill any of the exclusion criteria for the study. Exclusion Criteria: Body Mass Index of >=30 kg/m^2 at baseline (increased to 35 kg/m^2 in protocol amendment 1 Liver transaminase (ALT, AST) >1.5 times the upper limit of normal and with no active liver disease at baseline Evidence of current myopathy (excluding subjects with CK >1.5 times above the upper limit of normal at baseline Clinical lab tests (CBC, blood chemistries, urinalysis) results outside the normal range or unacceptable to the investigator at baseline Type II diabetes mellitus that was poorly controlled (HbA1c>9%), newly diagnosed, or changed their anti-diabetic therapy within 3 months of baseline Type I diabetes mellitus and not on a stable insulin regimen for 3 months prior to baseline or who had a recent history of repeated hypoglycaemia or unstable glycaemic control Known hypersensitivity to HMG-CoA reductase inhibitors Alcohol consumption >14 units (women)/21 units (men) (unit = 0.5 pint of beer or wine, or single measure of spirits) Pregnancy, lactation, or any condition or situation which, in the opinion of the investigator, posed a risk to the subject or interfered with participation in this study. Any of the following medical conditions: HIV positive; congestive heart failure defined by NYHA as Class III or IV; uncontrolled cardiac arrhythmia; MI, acute coronary insufficiency, CABG, or angioplasty within 3 months of baseline; unstable or severe peripheral artery disease within 3 months of baseline; newly diagnosed or unstable angina pectoris at baseline; uncontrolled hypertension with systolic blood pressure >100 mm Hg at baseline; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins; impaired renal function or nephritic syndrome at baseline; disorders of the hematological, gastrointestinal, or central nervous systems; diseases other than hyperlipidaemia or coronary heart disease that would have interfered with study evaluations; and cancer. Drug abuse or emotional or intellectual problems; Use of certain drugs, food, or other agents known to alter cholesterol levels or to cause pharmacokinetic interactions with either ezetimibe or atorvastatin

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ezetimibe + Atorvastatin<br> | Drug: Ezetimibe + Atorvastatin<br>* oral tablets: ezetimibe 10 mg + atorvastatin 10 mg once daily for 6 weeks<br>* Other names: Lipitor;|
| Active Comparator: Atorvastatin<br> | Drug: Atorvastatin<br>* oral tablets: atorvastatin 10 mg + ezetimibe placebo once daily for 6 weeks<br>* Other names: Lipitor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change in LDL-C from baseline to endpoint. |  | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent change from baseline to endpoint in total cholesterol, HDL-C and triglycerides. |  | 6 weeks | 
| Safety: adverse events, laboratory test results, vital signs. |  | Throughout study |