Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)(COMPLETED)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by:
Schering-Plough
ClinicalTrials.gov Identifier:
NCT00413972
First received: December 19, 2006
Last updated: June 3, 2010
Last verified: June 2010
  Purpose

This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group Phase 3 study of Vytorin 10/10 (ezetimibe 10 mg with simvastatin 10 mg), Vytorin 10/20 (ezetimibe 10 mg with simvastatin 20 mg), and Vytorin 10/40 (ezetimibe 10 mg with simvastatin 40 mg) compared to placebo administered daily for 8 consecutive weeks in subjects with primary hypercholesterolemia (LDL-C >3.64 mmol/L [140 mg/dL]). The efficacy of daily Vytorin versus placebo in reducing the concentration of LDL-C will be evaluated, and the efficacy of daily Vytorin versus placebo with respect to change in the concentrations of total cholesterol, triglycerides, and HDL-C will be compared. The safety of Vytorin versus placebo will also be assessed.


Condition Intervention Phase
Hypercholesterolemia
Drug: ezetimibe with simvastatin
Drug: Ezetimibe with Simvastatin
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Double-blind, Randomized, Placebo-controlled Parallel Groups Study Comparing the Efficacy and Safety of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia

Resource links provided by NLM:


Further study details as provided by Schering-Plough:

Primary Outcome Measures:
  • Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint After 8 Weeks of Treatment [ Time Frame: Baseline, 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 392
Study Start Date: April 2006
Study Completion Date: November 2006
Arms Assigned Interventions
Experimental: Vytorin 10/10
Ezetimibe 10 mg with Simvastatin 10 mg
Drug: ezetimibe with simvastatin
Ezetimibe 10 mg with Simvastatin 10 mg once daily for a total of eight weeks
Experimental: Vytorin 10/20
Ezetimibe 10 mg with Simvastatin 20 mg
Drug: Ezetimibe with Simvastatin
Ezetimibe 10 mg with Simvastatin 20 mg once daily for a total of eight weeks
Experimental: Vytorin 10/40
Ezetimibe 10 mg with Simvastatin 40 mg
Drug: Ezetimibe with Simvastatin
Ezetimibe 10 mg with Simvastatin 40 mg once daily for a total of eight weeks
Placebo Comparator: Placebo Drug: Placebo
Placebo once daily for a total of eight weeks

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must be >=18 years and <=75 years of age, male or female.
  • Primary hypercholesterolemic subject with a plasma LDL cholesterol concentration >3.64 mmol/L (140 mg/dL) to <=6.3 mmol/L (250 mg/dL) using the Friedewald calculation; total cholesterol (TC) >5.2 mmol/L (200 mg/dL) to <12.7 mmol/L (500 mg/dL) and triglyceride concentrations of <=3.99 mmol/L (350 mg/dL) should be met at the same time. At the time of recruitment (Visit 1), these values may be lower if the subject is on lipid-lowering therapy. (ie, prior to the start of lipid lowering drug washout) or may be higher at the start of dietary therapy.
  • Liver transaminases (ALT, AST) <=50% above the upper limit of normal, with no active liver disease and CK <=50% above the upper limit of normal.
  • Clinical laboratory tests (complete blood count [CBC], blood chemistries, urinalysis) must be within normal limits, or clinically acceptable to the investigator/sponsor.
  • 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.
  • 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.
  • Subject must agree to remain on a cholesterol-lowering diet for the duration of the study (according to China Adult Treatment Panel of High Blood Cholesterol).

Exclusion Criteria:

  • Subjects whose body mass index (BMI=weight [kg]/height2 [m]) is >=30 kg/m2 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.
  • 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 at study entry.
  • Uncontrolled (as determined by fasting glucose >180 mg/mL or HbA1c >9%) or newly diagnosed (within 1 month of study entry) diabetes mellitus.
  • Uncontrolled endocrine or metabolic disease known to influence serum lipids or lipoproteins, ie, secondary causes of hyperlipidemia, such as secondary hypercholesterolemia due to hypothyroidism (thyroid stimulating hormone [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 at 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.
  • Female subject receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives.
  Contacts and Locations
No Contacts or Locations Provided
  More Information

No publications provided

Responsible Party: Head, Clinical Trials Registry & Results Disclosure Group, Schering-Plough
ClinicalTrials.gov Identifier: NCT00413972     History of Changes
Other Study ID Numbers: P04420, SCH 465981
Study First Received: December 19, 2006
Results First Received: April 28, 2010
Last Updated: June 3, 2010
Health Authority: China: Ministry of Health

Additional relevant MeSH terms:
Hypercholesterolemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases
Simvastatin
Ezetimibe
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Lipid Regulating Agents
Therapeutic Uses
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Anticholesteremic Agents
Enzyme Inhibitors

ClinicalTrials.gov processed this record on April 17, 2014