Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)
Primary Purpose
Hypercholesterolemia
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ezetimibe with simvastatin
Ezetimibe with Simvastatin
Ezetimibe with Simvastatin
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Hypercholesterolemia
Eligibility 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Placebo Comparator
Arm Label
Vytorin 10/10
Vytorin 10/20
Vytorin 10/40
Placebo
Arm Description
Ezetimibe 10 mg with Simvastatin 10 mg
Ezetimibe 10 mg with Simvastatin 20 mg
Ezetimibe 10 mg with Simvastatin 40 mg
Outcomes
Primary Outcome Measures
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint After 8 Weeks of Treatment
Secondary Outcome Measures
Full Information
NCT ID
NCT00413972
First Posted
December 19, 2006
Last Updated
February 7, 2022
Sponsor
Organon and Co
Collaborators
Schering-Plough, Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00413972
Brief Title
Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
November 2006 (Actual)
Study Completion Date
November 2006 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Organon and Co
Collaborators
Schering-Plough, Merck Sharp & Dohme LLC
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercholesterolemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
392 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vytorin 10/10
Arm Type
Experimental
Arm Description
Ezetimibe 10 mg with Simvastatin 10 mg
Arm Title
Vytorin 10/20
Arm Type
Experimental
Arm Description
Ezetimibe 10 mg with Simvastatin 20 mg
Arm Title
Vytorin 10/40
Arm Type
Experimental
Arm Description
Ezetimibe 10 mg with Simvastatin 40 mg
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
ezetimibe with simvastatin
Intervention Description
Ezetimibe 10 mg with Simvastatin 10 mg once daily for a total of eight weeks
Intervention Type
Drug
Intervention Name(s)
Ezetimibe with Simvastatin
Intervention Description
Ezetimibe 10 mg with Simvastatin 20 mg once daily for a total of eight weeks
Intervention Type
Drug
Intervention Name(s)
Ezetimibe with Simvastatin
Intervention Description
Ezetimibe 10 mg with Simvastatin 40 mg once daily for a total of eight weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo once daily for a total of eight weeks
Primary Outcome Measure Information:
Title
Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint After 8 Weeks of Treatment
Time Frame
Baseline, 8 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility 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.
12. IPD Sharing Statement
Learn more about this trial
Effects of Vytorin Versus Placebo in Subjects With Primary Hypercholesterolemia (Study P04420)
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