Official Title: “SCH 58235: A Multicenter, Randomised, Parallel Groups, Placebo-Controlled Study Comparing The Efficacy, Safety, and Tolerability Of The Daily Co-Administration of Ezetimibe 10 mg With Simvastatin 20 mg vs Ezetimibe Placebo With Simvastatin 20 mg in Untreated Subjects With Primary Hypercholesterolaemia And Coronary Heart Disease (Protocol P03435)”

This study will assess whether co-administration of ezetimibe 10 mg with simvastatin 20 mg will be more effective than treatment with simvastatin 20 mg alone in reducing LDL-C concentrations when administered for 6 weeks.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2004

Intervention(s) in this Clinical Trial

• Drug: Ezetimibe + Simvastatin
  • oral tablets: ezetimibe 10 mg + simvastatin 20 mg once daily for 6 weeks
• Drug: Simvastatin
  • oral tablets: simvastatin 20 mg + ezetimibe placebo once daily for 6 weeks

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Ezetimibe + Simvastatin
• Active Comparator: Simvastatin

Primary Measures

• Percent change in LDL-C from baseline to endpoint.
  • Time Frame: 6 weeks
    Safety Issue?: No

Secondary Measures

• Percent of subjects who achieve LDL-C ESC goal (ie, <3 mmol/L [115 mg/dL]) at endpoint.
  • Time Frame: 6 weeks
    Safety Issue?: No
• Percent change from baseline to endpoint in total cholesterol, HDL-C and triglycerides.
  • Time Frame: 6 weeks
    Safety Issue?: No
• Safety: adverse events, laboratory test results, vital signs.
  • Time Frame: Throughout study
    Safety Issue?: Yes

Inclusion Criteria:

• >=18 years and <= 75 years of age
• LDL-C concentration >= 3.3 mmol/L (130 mg/dL) to <= 4.9 mmol/L (190 mg/dL) at baseline.
• Triglyceride concentration <3.99 mmol/L (350 mg/dL) at baseline.
• Documented coronary heart disease (CHD), which will include one or more of the following features: documented stable angina (with evidence of ischemia on exercise testing); history of MI; history of PCI (primarily PTCA with or without stent replacement); symptomatic peripheral vascular disease; documented history of atherothrombotic cerebrovascular disease; and/or documented history of non-Q wave MI.
• Stable weight history for at least 4 weeks prior to entry into study at baseline.
• Female subjects of childbearing potential must be using an acceptable method of birth control or be surgically sterilized.

Exclusion Criteria:

• Body mass index (BMI) >=35 kg/m^2 at baseline.
• Subjects whose liver transaminases (ALT, AST) are >1.5 times the upper limit of normal and with active liver diseases at baseline.
• Subjects with evidence of current myopathy (including subjects with CK>1.5 times above the upper limit of normal) at baseline.
• Subjects with clinical laboratory tests (CBC, blood chemistries, urinalysis) outside the normal range that are clinically acceptable to the investigator at baseline.
• Subjects with Type II diabetes mellitus who are poorly controlled (HbA1c>9%) or newly diagnosed (within 3 months) or who have had a change in anti-diabetic therapy within 3 months of baseline.
• Subjects with Type I diabetes mellitus who have not been on a stable insulin regimen for 3 months prior to baseline, or who have a recent history of repeated hypoglycaemia or unstable glycaemic control.
• Subjects who have known hypersensitivity to HMG-CoA reductase inhibitors.
• Female subjects who consume >14 units and male subjects who consume >21 units of alcohol per week.
• Female subjects who are pregnant or breast feeding.
• Subjects who have not observed the designated washout periods for any of the prohibited medications.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 75 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Schering-Plough

Information obtained from ClinicalTrials.gov on September 05, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00653835

Study ID Number: P03435

ClinicalTrials.gov Identifier: NCT00653835

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency