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

NCT00413972 | Completed Phase 3 Results

• 2 other identifiers: P04420SCH 465981
• Study Type: interventional
• Target: 392
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hypercholesterolemia

Outcome Measures

Primary Outcomes (1)

• Percent Change in Low-density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint After 8 Weeks of Treatment

  Baseline, 8 weeks

Study Arms (4)

Vytorin 10/10

EXPERIMENTAL

Ezetimibe 10 mg with Simvastatin 10 mg

Drug: ezetimibe with simvastatin

Vytorin 10/20

EXPERIMENTAL

Ezetimibe 10 mg with Simvastatin 20 mg

Drug: Ezetimibe with Simvastatin

Vytorin 10/40

EXPERIMENTAL

Ezetimibe 10 mg with Simvastatin 40 mg

Drug: Ezetimibe with Simvastatin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Ezetimibe with Simvastatin DRUG

Ezetimibe 10 mg with Simvastatin 10 mg once daily for a total of eight weeks

Vytorin 10/10

Placebo DRUG

Placebo once daily for a total of eight weeks

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Hypercholesterolemia

Interventions

Ezetimibe; Simvastatin

Condition Hierarchy (Ancestors)

Hyperlipidemias; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: December 19, 2006
• First Posted: December 20, 2006
• Study Start: April 1, 2006
• Primary Completion: November 1, 2006
• Study Completion: November 1, 2006
• Last Updated: February 9, 2022
• Results First Posted: May 25, 2010

Record last verified: 2022-02