HypercholesterolemiaPhase 4NCT00423579
The Effects of Ezetimibe/Simvastatin 10/20 mg Versus Simvastatin 40 mg in High Cholesterol and Coronary Heart Disease Study (P04039AM2)(COMPLETED)
A Phase 4 study testing Ezetimibe/Simvastatin 10/20 mg and simvastatin 40 mg in people with Hypercholesterolemia and Coronary Disease, run by Organon and Co.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypercholesterolemia, Coronary Disease
- What is being tested?
- Ezetimibe/Simvastatin 10/20 mg and simvastatin 40 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2006to 1 Mar 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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.
Who cannot join
- 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.
- Exclusion Criteria: subjects who have the following medical conditions:
- Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV.
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- Uncontrolled cardiac arrhythmia.
- Myocardial infarction, acute coronary insufficiency, coronary artery bypass surgery, or angioplasty within 3 months of Visit 3 (Baseline Visit).
- Unstable or severe peripheral artery disease within 3 months of Visit 3 (Baseline Visit).
- Newly diagnosed or currently unstable angina pectoris (chest pain).
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure > 160 mm Hg or diastolic > 100 mm Hg at Visit 3 (Baseline Visit).
- Type I or Type II 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 (thyroid stimulating hormone [TSH] above upper limit of normal) at Visit 3. 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 at Visit 3 (Baseline Visit).
- Impaired renal function (creatinine > 2.0 mg/dL) or nephrotic syndrome at Visit 3 (Baseline Visit).
- Disorders of the hematologic, digestive, or central nervous systems including cerebrovascular disease and degenerative disease that would limit study evaluation or participation.
- Known Human Immunodeficiency Virus (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.
- Exclusion Criteria: subjects who are on any of the following concomitant medications:
- Subjects who have not observed the designated wash-out period for any of the prohibited medications.
- Subjects who have not stopped taking various prohibited medications for a minimum period of time before Visit 3, including amiodarone hydrochloride (6 months) and probucol (12 months).
- Subjects currently consuming large amounts of grapefruit juice (> 1 liter/day).
- Oral corticosteroids, unless used as replacement therapy for pituitary/adrenal disease and the subject is on a stable regimen for at least 6 weeks prior to Visit 3 (Baseline Visit).
- Subjects who are currently using cardiovascular medication (e.g. antihypertensive, antiarrhythmic) and have not been on a stable regimen for at least 6 weeks prior to Visit 3 (Baseline Visit) and it is expected to change during the study.
- Subjects who are currently using psyllium, other fiber-based laxatives, and/or any other over-the-counter (OTC) therapy known to affect serum lipid levels (phytosterol margarine), and have not been on a stable regimen for at least 5 weeks prior to study entry Visit 3 (Baseline Visit) and who do not agree to remain on this regimen throughout the study.
- Subject who are currently using orlistat or sibutramine.
- Subjects who are currently using amiodarone hydrochloride.
- Subjects who are currently using danazol.
- Subjects who are currently using coumarin anticoagulants (warfarin).
- Subjects who are using (at the Screening Visit / Visit 1) any statin other than simvastatin 20 mg, or ezetimibe alone or in combination with any statin (including the fixed combination with simvastatin).
About this study
Official title: A Multicenter, Randomized, Parallel-Groups, Double-Blind Placebo-Controlled Study Comparing the Efficacy, Safety, and Tolerability of Administration of Ezetimibe/Simvastatin Tablet 10/20 mg Versus Doubling the Dose of Simvastatin 20 mg [Simvastatin 40 mg] in Subjects With Primary Hypercholesterolemia and Coronary Heart Disease
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.
- Conditions
- Hypercholesterolemia, Coronary Disease
- Being tested
- Ezetimibe/Simvastatin 10/20 mg, simvastatin 40 mg
- Medical subject headings
- Hypercholesterolemia, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ezetimibe/Simvastatin 10/20 mgDrug
1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks
simvastatin 40 mgDrug
1 tablet containing 40 mg of simvastatin per day for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo | Experimental | 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 Receives: Drug: Ezetimibe/Simvastatin 10/20 mg |
| Ezetimibe/Simvastatin placebo + Simvastatin 40 mg | Active comparator | 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. Receives: Drug: simvastatin 40 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jan 2007 (estimated)
- Study start1 Jul 2006
- Primary completion1 Mar 2008
- Study completion1 Mar 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Schering-Plough
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00423579
- Sponsor's protocol ID
- P04039
- Status last verified
- Feb 2022
- First submitted
- 17 Jan 2007
- Last updated
- 22 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Averna M, Zaninelli A, Le Grazie C, Gensini GF. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. J Clin Lipidol. 2010 Jul-Aug;4(4):272-8. doi: 10.1016/j.jacl.2010.05.002. Epub 2010 Jun 1.
PubMed 21122660Rotella CM, Zaninelli A, Le Grazie C, Hanson ME, Gensini GF. Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes. Lipids Health Dis. 2010 Jul 27;9:80. doi: 10.1186/1476-511X-9-80.
PubMed 20663203
Study at a glance
From the registry record, last updated by the sponsor on 22 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Parallel-Groups, Double-Blind Placebo-Controlled Study Comparing the Efficacy, Safety, and Tolerability of Administration of Ezetimibe/Simvastatin Tablet 10/20 mg Versus Doubling the Dose of Simvastatin 20 mg [Simvastatin 40 mg] in Subjects With Primary Hypercholesterolemia and Coronary Heart Disease
- ClinicalTrials.gov ID
- NCT00423579
- Acronym / sponsor ID
- P04039
- Conditions
- Hypercholesterolemia, Coronary Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Collaborators
- Schering-Plough
- Study start
- 1 Jul 2006 (actual)
- Primary completion
- 1 Mar 2008 (actual)
- Study completion
- 1 Mar 2008 (actual)
- First posted
- 18 Jan 2007 (estimated)
- Results
- Posted 25 Aug 2009
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo | Experimental | Drug: Ezetimibe/Simvastatin 10/20 mgSubjects 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 |
| Ezetimibe/Simvastatin placebo + Simvastatin 40 mg | Active comparator | Drug: simvastatin 40 mgSubjects 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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).
Key exclusion criteria (30 listed)
- 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.
- Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ezetimibe/Simvastatin 10/20 mg1 tablet containing 10 mg of ezetimibe and 20 mg of simvastatin per day for 6 weeks | Drug | Ezetimibe/Simvastatin 10/20 mg + Simvastatin placebo |
| simvastatin 40 mg1 tablet containing 40 mg of simvastatin per day for 6 weeks | Drug | Ezetimibe/Simvastatin placebo + Simvastatin 40 mg |
Primary outcome
Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks
Time frame: Baseline and 6 weeks
Percentage change in LDL C from baseline to endpoint after 6 weeks of treatment.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 21122660Averna M, Zaninelli A, Le Grazie C, Gensini GF. Ezetimibe/simvastatin 10/20 mg versus simvastatin 40 mg in coronary heart disease patients. J Clin Lipidol. 2010 Jul-Aug;4(4):272-8. doi: 10.1016/j.jacl.2010.05.002. Epub 2010 Jun 1.
- Derived from this study: PubMed 20663203Rotella CM, Zaninelli A, Le Grazie C, Hanson ME, Gensini GF. Ezetimibe/simvastatin vs simvastatin in coronary heart disease patients with or without diabetes. Lipids Health Dis. 2010 Jul 27;9:80. doi: 10.1186/1476-511X-9-80.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ezetimibe/Simvastatin 10/20 mg and simvastatin 40 mg in people with Hypercholesterolemia and Coronary Disease, run by Organon and Co.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 May 2024. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Aug 2009). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Low-density-lipoprotein Cholesterol (LDL-C) at 6 Weeks (time frame: Baseline and 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00423579, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 May 2024.