Status:

COMPLETED

Efficacy and Safety Study of Ezetimibe (SCH 58235, MK-0653) in Addition to Atorvastatin in Participants With Coronary Heart Disease or Multiple Cardiovascular Risk Factors (P00693/MK-0653-030)

Lead Sponsor:

Organon and Co

Conditions:

Hypercholesterolemia

Eligibility:

All Genders

18+ years

Phase:

PHASE3

Brief Summary

The overall objective is to evaluate the efficacy and safety of ezetimibe (SCH 058235/MK-0653) 10 mg administered daily in conjunction with atorvastatin in participants with Heterozygous Familial Hype...

Eligibility Criteria

Inclusion

  • Primary hypercholesterolemic participants with known coronary heart disease (CHD) or multiple risk factors for CHD (≥2) not meeting the target low-density-lipoprotein cholesterol (LDL-C) of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma triglycerides (TG) ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin at least 4 weeks before initial qualifying lipid determination.
  • Participants with heterozygous familial hypercholesterolemia (HeFH) not meeting the target LDL-C of ≤100 mg/dL (2.59 mmol/L), with plasma LDL-C ≥130 mg/dL (3.37 mmol/L) and plasma TG ≤350 mg/dL (3.99 mmol/L) while on starting-dose (10 mg) atorvastatin for at least 4 weeks before initial lipid qualifying determination. HeFH is defined by: a) genetic testing; or b) LDL-C \>190 mg/dL (4.9 mmol/L) and at least one of the following: (1) xanthomata in first or second degree relative; (2) family history of myocardial infarction under age 60 years in a first degree relative or family history of myocardial infarction under age 50 years in a second degree relative; (3) family history of total cholesterol (TC) \>290 mg/dL (\>7.5 mmol/L) in a first or second degree relative.
  • All women must have a negative pregnancy test prior to study entry. Women of child-bearing potential must agree to practice an effective barrier method of birth control for the duration of the study, as well as for 1 month following study completion.
  • Postmenopausal women who are receiving postmenopausal hormonal therapy or raloxifene must be maintained on a stable estrogen replacement therapy (ERT), estrogen/progestin hormone replacement therapy (HRT) or raloxifene regimen during the study period.
  • Participants must be willing to observe the National Cholesterol Education Program (NCEP) Step I diet as determined by a Ratio of Ingested Saturated fat and Cholesterol to Calories (RISCC) score not greater than 24 throughout this study. Ability to complete diet diaries needs to be demonstrated.

Exclusion

  • Individuals with a history of mental instability, drug/alcohol abuse within the past 5 years or individuals who have been treated or are being treated for severe psychiatric illness which in the opinion of the Investigator, may interfere with optimal participation in the study.
  • Underlying disease likely to limit life span to less than 1 year.
  • Participants who have previously been randomized in any of the studies evaluating ezetimibe.
  • Participants with known hypersensitivity or any contraindication to atorvastatin
  • Pregnant or lactating women.
  • Participants with congestive heart failure New York Heart Association (NYHA) Class III or IV.
  • Participants with uncontrolled cardiac arrhythmias
  • Participants with myocardial infarction, coronary bypass surgery or angioplasty within 3 months of study entry.
  • Participants with unstable or severe peripheral artery disease within 3 months of study entry.
  • Participants with unstable angina pectoris.
  • Participants with disorders of the hematologic, digestive or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
  • Participants with uncontrolled (as determined by hemoglobin A1c \[HbA1c\]) or newly diagnosed (within 1 month of study entry) diabetes mellitus.
  • Participants with uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins. Clinically euthyroid participants on replacement doses of thyroid hormone are eligible for enrollment.
  • Participants with known impairment of renal function (creatinine \>2.0 mg/dL), dysproteinemia, nephrotic syndrome or other renal disease (24-hour urinary protein 3+ or 1 gram).
  • Participants with active or chronic hepatobiliary or hepatic disease (participants with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>2 times the upper limit of the central laboratory reference range \[ULN\] will be excluded).
  • Participants who are known to be human immunodeficiency virus (HIV) positive.
  • Participants with known coagulopathy (prothrombin time \[PT\] or partial thromboplastin time \[PTT\] at Visit 2 \>1.25 times control).

Key Trial Info

Start Date :

April 24 2000

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

November 16 2001

Estimated Enrollment :

621 Patients enrolled

Trial Details

Trial ID

NCT03867318

Start Date

April 24 2000

End Date

November 16 2001

Last Update

May 10 2024

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