Hypercholesterolemia, Coronary Disease
Conditions
Brief summary
This study is being conducted to compare the efficacy, safety, and tolerability of ezetimibe/simvastatin 10/20 mg when administered daily versus doubling the dose of simvastatin to 40 mg in patients with hypercholesterolemia and coronary heart disease.
Interventions
DRUGEzetimibe/Simvastatin 10/20 mg
1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks
1 tablet containing 40 mg of simvastatin per day for 6 weeks
Sponsors
Schering-Plough
Organon and Co
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects must have documented coronary heart disease (CHD). For the purposes of this study, CHD will include one or more of the following features: documented stable angina (with evidence of ischemia on exercise testing); history of myocardial infarction; history of percutaneous coronary intervention \[PCI\] (primarily PCI with or without stent placement); symptomatic peripheral vascular disease (claudication); documented history of atherothrombotic cerebrovascular disease; and/or documented history of unstable angina or non-Q wave myocardial infarction. * Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent. * History of myocardial infarction (heart attack). * Subjects must be \>= 18 years and \<= 75 years of age. * Subjects must have an LDL-C concentration \>= 2.6 mmol/L (100 mg/dL) to \<= 4.1 mmol/L (160 mg/dL) at the time of randomization (Visit 3/Baseline Visit). * Subjects must have triglyceride concentrations of \< 3.99 mmol/L (350 mg/dL) at (Visit 3 Baseline Visit). * Subject must be currently taking simvastatin 20 mg daily. * Subjects must have liver transaminases (ALT \[alanine aminotransferase\], AST \[aspartate aminotransferase\]) \< 50% above the upper limit of normal, with no active liver disease, and CK (creatine kinase) \< 50% above the upper limit of normal at Visit 3 (Baseline Visit). * Clinical laboratory tests (complete blood count \[CBC\], blood chemistries, urinalysis) must be within normal limits or clinically acceptable to the investigator at Visit 3 (Baseline Visit). * Subjects must have maintained a cholesterol-lowering diet and exercise program for at least 4 weeks prior to the study and be willing to continue the same diet and exercise program during the study. * Subjects must report a stable weight history for at least 4 weeks prior to entry into study at Visit 3 (Baseline Visit). * Women receiving hormonal therapy, including hormone replacement, any estrogen antagonist/agonist, or oral contraceptives, must have been maintained on a stable dose and regimen for at least 8 weeks and be willing to continue the same regimen for the duration of the study. * 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., hormonal contraceptive, medically prescribed intrauterine device \[IUD\], 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 or coronary heart disease 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 their cholesterol-lowering diet and their exercise regimen for the duration of the study.
Exclusion criteria
* Subjects whose body mass index (BMI = weight \[kg\]/height2 \[m\]) is \>= 35 kg/m\^2 at Visit 3 (Baseline Visit). * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks | Baseline and 6 weeks | Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment. |
Participant flow
Pre-assignment details
Visits 1 and 2 were for screening, combined if wash-out not required. One ineligible subject mistakenly received assignment at Visit 2 and was removed. The subject did not receive treatment. Actual enrollment: 120 subjects. Intent-to-treat (ITT) population included only evaluable subjects; as such analysis based on 112 subjects.
Participants by arm
| Arm | Count |
|---|---|
| Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo Subjects in the Intent-to-Treat Population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin 10/20 mg. The second tablet is simvastatin placebo. Subjects will receive a maximum of 6 weeks of treatment | 56 |
| Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg Subjects in the Intent-to-Treat population. Subjects will receive 2 tablets. The first tablet is Ezetimibe/Simvastatin placebo. The second tablet is simvastatin 40 mg. Subjects will receive a maximum of 6 weeks of treatment. | 56 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Diagnosis of diabetes | 0 | 1 |
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Protocol Violation | 1 | 3 |
Baseline characteristics
| Characteristic | Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo | Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg | Total |
|---|---|---|---|
| Age, Continuous | 61.3 years STANDARD_DEVIATION 8.4 | 62.1 years STANDARD_DEVIATION 7.8 | 61.7 years STANDARD_DEVIATION 8.1 |
| Sex: Female, Male Female | 26 Participants | 24 Participants | 50 Participants |
| Sex: Female, Male Male | 30 Participants | 32 Participants | 62 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 60 | 0 / 60 |
| serious Total, serious adverse events | 0 / 60 | 1 / 60 |
Outcome results
Primary
Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks
Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment.
Time frame: Baseline and 6 weeks
Population: Intent-to-treat population only.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ezetimibe/Simvastatin 10/20 mg + Simvastatin Placebo | Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks | -26.5 percentage change | Standard Deviation 9.5 |
| Ezetimibe/Simvastatin Placebo + Simvastatin 40 mg | Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks | -11.9 percentage change | Standard Deviation 13.6 |
p-value: 095% CI: [-18.9, -10.1]Student's t test for independent data