Effect of Ezetimibe Plus Simvastatin on Flow-Mediated Brachial Artery Vasoactivity in Subjects With Primary Hypercholesterolemia (Study P03336)

NCT00651391 | Terminated Phase 3

• 1 other identifier: P03336
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this study is to evaluate the effect of ezetimibe coadministered with simvastatin compared with simvastatin alone when administered for 12 weeks on endothelial function as assessed by brachial artery reactivity testing (BART) using high-frequency ultrasound to image the brachial artery vasomotor response to a flow-mediated stimulus (high-shear stress) in subjects with high cholesterol. The secondary objectives include evaluation of nitroglycerin-induced vasodilation. In addition, lipid parameters (low-density-lipoprotein cholesterol \[LDL-C\], high-density-lipoprotein cholesterol \[HDL-C\], triglycerides \[TG\], total cholesterol \[TC\]) and C reactive protein (CRP) will be assessed by treatment group.

Conditions

Hypercholesterolemia; Atherosclerosis

Outcome Measures

Primary Outcomes (1)

• Change from baseline to endpoint in flow-mediated vasodilation: percent change in the mean diameter between 1-minute, post-cuff release diameter and image obtained prior to cuff application.

  Week 12

Secondary Outcomes (2)

• Change from baseline to endpoint in NTG-induced vasodilation: percent change in the diameter between the post-NTG and pre-NTG diameters.

  Week 12

• Changes from baseline to endpoint in LDL-C, HDL-C, TG, TC, and CRP.

  Week 12

Study Arms (3)

Ezetimibe + Simvastatin

EXPERIMENTAL

Drug: Ezetimibe + Simvastatin

Simvastatin

ACTIVE COMPARATOR

Drug: Simvastatin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ezetimibe + Simvastatin DRUG

oral tablet of ezetimibe 10 mg plus simvastatin 20 mg once daily in the evening for 12 weeks

Also known as: SCH 58235

Ezetimibe + Simvastatin

Simvastatin DRUG

oral simvastatin 20 mg once daily in the evening for 12 weeks

Simvastatin

Placebo DRUG

oral placebo once daily in the evening for 12 weeks

Placebo

Eligibility Criteria

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

You may qualify if:

• Adults (18 years old and older) with primary hypercholesterolemia with a plasma LDL-C \>=145 mg/dL and \<=250 mg/dL, and plasma TG \<=350 mg/dL after adequate drug washout.
• Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable hormone replacement therapy (HRT) or raloxifene regimen for at least 6 weeks prior to study entry and throughout the study period.
• All subjects must agree to refrain from drinking alcohol or caffeine containing beverages for 12 hours prior to each study visit at which a BART assessment is performed; be minimally active (eg, avoid excessive physical activity) for 12 hours prior to each study visit at which a BART assessment is performed; and be willing to observe the NCEP Step I diet, participate in the study, and complete all study-related procedures.

You may not qualify if:

• Pregnancy or any other situation, condition, or illness that, in the opinion of the investigator, may interfere with optimal participation in the study
• Smoking, excessive alcohol consumption, underlying disease likely to limit life span to less than one year, or known hypersensitivity or any contraindication to simvastatin, ezetimibe, or nitroglycerin
• Existing hypercholesterolemia for which withholding approved lipid-lowering therapy for the duration of the study would be inappropriate
• The following concomitant illnesses: congestive heart failure NYHA Class III or IV; obstructive cardiomyopathy; uncontrolled cardiac arrhythmias; severe aortic stenosis; upper severe aortic stenosis; MI, CABG, or angioplasty within 6 months of study entry; uncontrolled hypertension; unstable or severe peripheral artery disease within 3 months of study entry; unstable angina pectoris; disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation; uncontrolled or newly diagnosed (within one month of study entry) diabetes mellitus; uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins (clinically euthyroid subjects on stable replacement doses of thyroid hormone are eligible for enrollment); known impairment of renal function (plasma creatinine \>2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram); hepatobiliary or hepatic disease (subjects with AST or ALT \>2 times the upper limit of reference range will be excluded); HIV positive; and known coagulopathy.
• Use of certain drugs, foods, or other agents known to alter lipid levels or to cause interactions with either ezetimibe or simvastatin

Sponsors & Collaborators

• Organon and Co: lead
• Merck Sharp & Dohme LLC: collaborator

MeSH Terms

Conditions

Hypercholesterolemia; Atherosclerosis

Interventions

Ezetimibe, Simvastatin Drug Combination; Ezetimibe; Simvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Drug Combinations; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2008
• First Posted: April 2, 2008
• Study Start: October 1, 2003
• Primary Completion: September 1, 2004
• Study Completion: September 1, 2004
• Last Updated: August 15, 2024

Record last verified: 2022-02