Comparison of Ezetimibe Plus Simvastatin Versus Ezetimibe or Simvastatin Alone in Subjects With Primary Hypercholesterolemia (Study P03757)(COMPLETED)

A Multicenter, Double-blind, Randomized, Active-controlled Parallel Groups Study Comparing The Efficacy and Safety of The Daily Co-Administration of Ezetimibe 10 mg With Simvastatin 20 mg Vs Simvastatin Or Ezetimibe Alone in Subjects With Primary Hypercholesterolemia

This is a multicenter, randomized, double blind; active-controlled parallel groups study enrolling subjects with primary hypercholesterolemia. Subjects receive ezetimibe, simvastatin, or the combination once daily for 8 weeks to determine the effect on LDL-cholesterol.

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia
• Intervention / Treatment: Drug: Ezetimibe + Simvastatin; Drug: Simvastatin; Drug: Ezetimibe

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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 with Primary Hypercholesterolemia must be finished the Lab test listed below and the results must be available at the time of randomization at Visit 3 (Baseline Visit).

  • LDL-C concentration > 3.64 mmol/L (140mg/dL) to <= 6.3 mmol/L (250 mg/dL) using the Friedewald calculation
  • Total cholesterol (TC) > 5.2mmol/L (200mg/dL) to < 12.7mmol/L (500mg/dL)
  • Triglyceride concentrations of <= 3.99 mmol/L (350 mg/dL)
  • Liver transaminases (ALT, AST) must be within normal limits, with no active liver disease and CK < 50% above the upper limit of normal
  • Clinical laboratory tests (CBC, blood chemistries, urinalysis) must be within normal limits
• Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 (Baseline Visit).
• 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. medically prescribed 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 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 a cholesterol-lowering diet for the duration of the study.

Exclusion Criteria:

• Subjects whose body mass index (BMI = weight [kg]/height2 [m]) is >= 30 Kg/m^2 at Visit 3 (Baseline Visit).
• Subjects who have known hypersensitivity to HMG-CoA reductase inhibitors.
• 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 outlined in protocol
• Congestive heart failure defined by NYHA as Class III or IV.
• Uncontrolled cardiac arrhythmia.
• Myocardial infarction, coronary bypass surgery or angioplasty within 6 months of study entry.
• Unstable or severe peripheral artery disease within 3 months of study entry.
• Unstable angina pectoris within 6 months of study entry.
• Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm Hg or diastolic > 100 mm Hg of study entry.
• Uncontrolled (as determined by HbA1c > 7 %) or newly diagnosed (within 1month of study entry) 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). 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 before enrollment.
• Known Impaired renal function (plasma creatinine > 2.0 mg/dL), or nephrotic syndrome of study entry.
• Disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
• Known HIV positive.
• Cancer within the past 5 years (except for successfully treated basal and squamous cell carcinomas).
• History of mental instability, drug/alcohol abuse within the past 5 years, or major psychiatric illness not adequately controlled and stable on pharmacotherapy.
• Subjects with known coagulopathy (PT and PTT at Visit 1 >1.25 times control)
• Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives.
• Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ezetimibe + Simvastatin	Drug: Ezetimibe + Simvastatin; ezetimibe 10 mg plus simvastatin 20 mg once daily for 8 weeks; Other Names: SCH 58235
Active Comparator: Simvastatin	Drug: Simvastatin; simvastatin 20 mg plus ezetimibe placebo once daily for 8 weeks
Active Comparator: Ezetimibe	Drug: Ezetimibe; Ezetimibe 10 mg plus simvastatin placebo once daily for 8 weeks; Other Names: SCH 58235

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in LDL-C concentration.	8 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Percent change from baseline in total cholesterol, triglycerides, and HDL-C.	8 weeks

Collaborators and Investigators

• Sponsor: Organon and Co
• Collaborators: Merck Sharp & Dohme LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2004
• Primary Completion (Actual): February 1, 2005
• Study Completion (Actual): February 1, 2005

Study Registration Dates

• First Submitted: March 31, 2008
• First Submitted That Met QC Criteria: March 31, 2008
• First Posted (Estimate): April 2, 2008

Study Record Updates

• Last Update Posted (Actual): February 16, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Hypercholesterolemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin; Ezetimibe
• Other Study ID Numbers: P03757

Plan for Individual participant data (IPD)

Study Data/Documents

1. CSR Synopsis