The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)

NCT00423579 | Completed Phase 4 Results

• 1 other identifier: P04039
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe/simvastatin 10/20 mg when administered daily versus doubling the dose of simvastatin to 40 mg in patients with hypercholesterolemia and coronary heart disease.

Conditions

Hypercholesterolemia; Coronary Disease

Outcome Measures

Primary Outcomes (1)

• Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks

  Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment.

  Baseline and 6 weeks

Study Arms (2)

Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo

EXPERIMENTAL

Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment

Drug: Ezetimibe/Simvastatin 10/20 mg

Ezetimibe/Simvastatin placebo + Simvastatin 40 mg

ACTIVE COMPARATOR

Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment.

Drug: simvastatin 40 mg

Interventions

Ezetimibe/Simvastatin 10/20 mg DRUG

1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks

Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo

simvastatin 40 mg DRUG

1 tablet containing 40 mg of simvastatin per day for 6 weeks

Ezetimibe/Simvastatin placebo + Simvastatin 40 mg

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 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 \[PCI\] (primarily PCI with or without stent placement); symptomatic peripheral vascular disease (claudication); documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-Q wave myocardial infarction.
• Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
• History of myocardial infarction (heart attack).
• 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) at the time of randomization (Visit 3/Baseline Visit).
• Subjects must have triglyceride concentrations of \< 3.99 mmol/L (350 mg/dL) at (Visit 3 Baseline Visit).
• Subject must be currently taking simvastatin 20 mg daily.
• Subjects must have liver transaminases (ALT \[alanine aminotransferase\], AST \[aspartate aminotransferase\]) \< 50% above the upper limit of normal, with no active liver disease, and CK (creatine kinase) \< 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).
• Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study.
• Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed intrauterine device \[IUD\], condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation).
• Subjects must be free of any clinically significant diseases other than hyperlipidemia or coronary heart disease that would interfere with study evaluations.
• Subjects must understand and be able to adhere to the dosing and visit schedules, and must agree to remain on their cholesterol-lowering diet and their exercise regimen for the duration of the study.

You may not qualify if:

• Subjects whose body mass index (BMI = weight \[kg\]/height2 \[m\]) is \>= 35 kg/m\^2 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.
• 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 (chest pain).
• Uncontrolled hypertension (treated or untreated) with systolic blood pressure \> 160 mm Hg or diastolic \> 100 mm Hg 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 (thyroid stimulating hormone \[TSH\] 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 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).
• Disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
• Known Human Immunodeficiency Virus (HIV) positive.

Sponsors & Collaborators

• Organon and Co: lead
• Schering-Plough: collaborator

Related Publications (2)

• Averna M, Zaninelli A, Le Grazie C, Gensini GF. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. J Clin Lipidol. 2010 Jul-Aug;4(4):272-8. doi: 10.1016/j.jacl.2010.05.002. Epub 2010 Jun 1.

  PMID: 21122660 DERIVED

• Rotella CM, Zaninelli A, Le Grazie C, Hanson ME, Gensini GF. Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes. Lipids Health Dis. 2010 Jul 27;9:80. doi: 10.1186/1476-511X-9-80.

  PMID: 20663203 DERIVED

MeSH Terms

Conditions

Hypercholesterolemia; Coronary Disease

Interventions

Ezetimibe; Simvastatin

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; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 17, 2007
• First Posted: January 18, 2007
• Study Start: July 1, 2006
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: May 22, 2024
• Results First Posted: August 25, 2009

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share