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

• Percent change from baseline to endpoint in total cholesterol, HDL-C and triglycerides. [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
• Safety: adverse events, laboratory test results, vital signs. [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

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.

• Hypercholesterolemia
• Atherosclerosis

• Drug: Ezetimibe + Atorvastatin
  oral tablets: ezetimibe 10 mg + atorvastatin 10 mg once daily for 6 weeks
  Other Names:

  • SCH 58235
  • Zetia
  • Lipitor
• Drug: Atorvastatin
  oral tablets: atorvastatin 10 mg + ezetimibe placebo once daily for 6 weeks
  Other Name: Lipitor

• Experimental: Ezetimibe + Atorvastatin
  Intervention: Drug: Ezetimibe + Atorvastatin
• Active Comparator: Atorvastatin
  Intervention: Drug: Atorvastatin

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