Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)

NCT00202904 | Completed Phase 4

• 1 other identifier: P03740
• Study Type: interventional
• Target: 81
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a multicenter, randomized, parallel group, placebo controlled study designed to evaluate the efficacy, safety, and tolerability of ezetimibe added to ongoing atorvastatin therapy compared with ongoing atorvastatin treatment alone. This study will involve subjects with primary hypercholesterolemia and coronary heart disease (CHD) who are currently being treated with atorvastatin and who would benefit from additional reduction in low-density lipoprotein cholesterol (LDL-C).

Conditions

Hypercholesterolemia; Coronary Heart Disease

Keywords

ezetimibe; atorvastatin; hypercholesterolemia; coronary heart disease

Outcome Measures

Primary Outcomes (1)

• To compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint

  after 6 weeks of treatment

Secondary Outcomes (3)

• To compare the percentage of subjects who achieve target LDL-C goal (as defined by the ESC or NCEP guidelines at the time of database lock) with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily

  after 6 weeks of treatment

• To compare the change in concentrations of total cholesterol, HDL-C and triglycerides with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily

  after 6 weeks of treatment

• To compare the safety and tolerability of ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily

  after 6 weeks of treatment

Study Arms (2)

Arm 1

EXPERIMENTAL

Drug: ezetimibe

Arm 2

ACTIVE COMPARATOR

Drug: placebo

Interventions

ezetimibe DRUG

ezetimibe 10 mg tablets, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks

Also known as: Zetia, SCH 58235

Arm 1

placebo DRUG

placebo tablets matched to ezetimibe, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks

Arm 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
• Subjects must be \>=18 years and \<=75 years of age.
• Subjects must have an LDL-C concentration \>=2.6 mmol/L (100 mg/dL) to \<=4.1 mmol/L (160 mg/dL) using the Friedewald calculation available at the time of randomization (Baseline Visit).
• Subjects must have triglyceride concentrations of \<3.99 mmol/L (350 mg/dL) at Visit 3 (Baseline Visit).
• Subjects must have documented coronary heart disease (CHD). For the purposes of this study, CHD will include one or more of the following features:
• Documented stable angina (with evidence of ischemia on exercise testing)
• History of myocardial infarction
• History of percutaneous coronary intervention (primarily percutaneous coronary transluminal angioplasty (PCTA) with or without stent placement)
• Symptomatic peripheral vascular disease (claudication)
• Documented history of unstable angina or non-Q wave myocardial infarction.
• Subject must be currently taking atorvastatin 10 mg daily and by history has taken 80% of daily doses for the preceding 6 weeks prior to Visit 3 (Baseline Visit).
• Subjects must have liver transaminases (alanine aminotransferase (ALT), aspartate aminotransferase (AST) \<50% above the upper limit of normal, with no active liver disease, and creatinine kinase (CK) \<50% above the upper limit of normal at Visit 3 (Baseline Visit).
• Clinical laboratory tests (complete blood count (CBC), blood chemistries, urinalysis) must be within normal limits or clinically acceptable to the investigator at Visit 3 (Baseline Visit).
• Subjects must have maintained a cholesterol lowering diet and exercise program for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study.
• Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 (Baseline Visit).

You may not qualify if:

• Subjects whose body mass index (BMI=weight \[kg\]/height2\[m\]) is \>=30 kg/m2 at Visit 3 (Baseline Visit).
• Subjects who consume \>14 alcoholic drinks per week. (A drink is: a can of beer, glass of wine, or single measure of spirits).
• Any condition or situation which, in the opinion of the investigator, might pose a risk to the subject or interfere with participation in the study.
• Women who are pregnant or nursing.
• Subjects who have not observed the designated washout periods for any of the prohibited medications.
• Subjects who have the following medical conditions:
• Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV.
• Uncontrolled cardiac arrhythmia.
• Myocardial infarction, acute coronary insufficiency, coronary artery bypass surgery, or angioplasty within 3 months of Visit 3 (Baseline Visit).
• Unstable or severe peripheral artery disease within 3 months of Visit 3 (Baseline Visit).
• Newly diagnosed or currently unstable angina pectoris.
• Uncontrolled hypertension (treated or untreated) with systolic blood pressure \>160 mmHg or diastolic \>100 mmHg at Visit 3 (Baseline Visit).
• Type I or Type II diabetes mellitus.
• Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, i.e., secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism (TSH above upper limit of normal) at Visit 3. Subjects with a history of hypothyroidism who are on a stable therapy of thyroid hormone replacement for at least 6 weeks are eligible for enrollment if thyroid-stimulating hormone (TSH) levels are within normal limits at Visit 3 (Baseline Visit).
• Impaired renal function (creatinine \> 2.0 mg/dL) or nephrotic syndrome at Visit 3 (Baseline Visit).

Sponsors & Collaborators

• Organon and Co: lead

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Disease

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2005
• First Posted: September 20, 2005
• Study Start: May 1, 2005
• Primary Completion: October 1, 2006
• Study Completion: October 1, 2006
• Last Updated: February 16, 2022

Record last verified: 2022-02