HypercholesterolemiaPhase 3NCT00423488
Ezetimibe and Simvastatin in Primary Hypercholesterolemia, Diabetes Mellitus Type 2, and Coronary Heart Disease (COMPLETED)
A Phase 3 study testing Ezetimibe 10 mg and Simvastatin 20 mg in people with Hypercholesterolemia and Diabetes Mellitus, Type 2, run by Organon and Co.
Trial summary
This multicenter, randomized, double-blind, placebo-controlled study will assess, after 6 weeks of dosing, whether co-administration of ezetimibe 10 mg with simvastatin 20 mg will be more effective than treatment with doubling the dose of simvastatin to 40 mg alone in reducing low-density lipoprotein-cholesterol… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypercholesterolemia, Diabetes Mellitus, Type 2, Coronary Disease
- What is being tested?
- Ezetimibe 10 mg and Simvastatin 20 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 93 participants
- Where
- No sites listed yet
- Study dates
- 12 Jul 2005to 16 Feb 2007
- Phase
- Phase 3
- 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
- Subject must have diabetes mellitus type 2 (fasting plasma glucose >7 mmol/L [126 mg/dL]) of at least 12 months duration at Visit 3 and must be adequately controlled (glycated hemoglobin [HbA1c] <=9.0%). Subjects must not have had a change in antidiabetic pharmacotherapy [i.e. changes in dosage (with the exception of +/- 10 units of insulin) or addition of new medication] or experience recent history of repeated hypoglycemia or unstable glycemic control within 3 months of Visit (Baseline Visit).
- 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 transluminal coronary intervention (PCTI) 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 have a low-density lipoprotein cholesterol (LDL-C) concentration >=2.6 mmol/L (100 mg/dL) to <=4.1 mmol/L (160 mg/dL) using the Friedewald calculation available 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 and by history has taken 80% of daily evening doses for the 6 weeks prior to Visit 3 (Baseline Visit).
- Subject must be >=18 years and <=75 years of age.
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- Subjects must have maintained a cholesterol lowering diet and exercise program for at least 4 weeks prior to Screening (Visit 2) and be willing to continue the same diet and exercise program during the study.
- Subjects must have liver transaminases (alanine aminotransferase [ALT], aspartate aminotransferase [AST]) <50% above the upper limit of normal, with no active liver disease, and creatinine kinase (CK)<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 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 diabetes mellitus 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
- Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
Who cannot join
- Subjects whose body mass index (BMI = weight[kg]/height[m]2) is >=35 kg/m2 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.
- Uncontrolled cardiac arrhythmia.
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- 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.
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic >100 mmHg at Visit 3 (Baseline Visit).
- 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.
- Subjects who have not observed the designated wash-out period for any of the prohibited medications.
- 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 lest 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.
About this study
Official title: A Multicenter, Randomized, Parallel-Groups, Double-Blind Placebo Controlled Study Comparing the Efficacy, Safety, and Tolerability of Co-administration of Ezetimibe 10 mg With Ongoing Treatment With Simvastatin 20 mg Versus Doubling the Dose of Simvastatin in Subjects With Primary Hypercholesterolemia Diabetes Mellitus Type 2 and Coronary Heart Disease
This multicenter, randomized, double-blind, placebo-controlled study will assess, after 6 weeks of dosing, whether co-administration of ezetimibe 10 mg with simvastatin 20 mg will be more effective than treatment with doubling the dose of simvastatin to 40 mg alone in reducing low-density lipoprotein-cholesterol (LDL-C) concentrations and in achieving the National Cholesterol Expert Panel (NCEP) III LDL-C target goal of <2.6 mmol/L (<100 mg/dL) for subjects with diabetes mellitus and coronary heart disease.
- Being tested
- Ezetimibe 10 mg, Simvastatin 20 mg, Ezetimibe Placebo, Simvastatin Placebo
- Medical subject headings
- Hypercholesterolemia, Diabetes Mellitus, Type 2, Coronary Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ezetimibe 10 mgDrug
1 x 10-mg tablet, provided as blinded study treatment
Simvastatin 20 mgDrug
1 x 20-mg tablet, provided as open-label study treatment
Ezetimibe PlaceboDrug
1 tablet matching ezetimibe 10-mg tablet, provided as blinded study treatment
Simvastatin 20 mgDrug
1 x 20-mg tablet, provided as blinded study treatment
Simvastatin PlaceboDrug
1 tablet matching 20-mg simvastatin tablet, provided as blinded study treatment
| Study group | Role | What they receive |
|---|---|---|
| Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg | Experimental | Participants were instructed to take one 10-mg ezetimibe tablet and one simvastatin placebo tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. Receives: Drug: Ezetimibe 10 mg; Drug: Simvastatin 20 mg; Drug: Simvastatin Placebo |
| Ezetimibe Placebo + Simvastatin 40 mg | Active comparator | Participants were instructed to take one ezetimibe placebo tablet and one simvastatin 20-mg tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. Receives: Drug: Simvastatin 20 mg; Drug: Ezetimibe Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint, After 6 Weeks of Treatment
Measured: 6 weeks of treatment (from Baseline to Endpoint)
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 start12 Jul 2005
- Primary completion16 Feb 2007
- Study completion16 Feb 2007
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 93 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
- NCT00423488
- Sponsor's protocol ID
- P04037
- Status last verified
- Feb 2022
- First submitted
- 17 Jan 2007
- Last updated
- 9 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Bardini G, Giorda CB, Pontiroli AE, Le Grazie C, Rotella CM. Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study). Cardiovasc Diabetol. 2010 May 21;9:20. doi: 10.1186/1475-2840-9-20.
PubMed 20492655Rotella 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 9 Feb 2022. 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 Co-administration of Ezetimibe 10 mg With Ongoing Treatment With Simvastatin 20 mg Versus Doubling the Dose of Simvastatin in Subjects With Primary Hypercholesterolemia Diabetes Mellitus Type 2 and Coronary Heart Disease
- ClinicalTrials.gov ID
- NCT00423488
- Acronym / sponsor ID
- P04037
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 93 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Collaborators
- Schering-Plough
- Study start
- 12 Jul 2005 (actual)
- Primary completion
- 16 Feb 2007 (actual)
- Study completion
- 16 Feb 2007 (actual)
- First posted
- 18 Jan 2007 (estimated)
- Results
- Posted 9 Mar 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This multicenter, randomized, double-blind, placebo-controlled study will assess, after 6 weeks of dosing, whether co-administration of ezetimibe 10 mg with simvastatin 20 mg will be more effective than treatment with doubling the dose of simvastatin to 40 mg alone in reducing low-density lipoprotein-cholesterol (LDL-C) concentrations and in achieving the National Cholesterol Expert Panel (NCEP) III LDL-C target goal of <2.6 mmol/L (<100 mg/dL) for subjects with diabetes mellitus and coronary heart disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg | Experimental | Drug: Ezetimibe 10 mg, Drug: Simvastatin 20 mg, Drug: Simvastatin PlaceboParticipants were instructed to take one 10-mg ezetimibe tablet and one simvastatin placebo tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. |
| Ezetimibe Placebo + Simvastatin 40 mg | Active comparator | Drug: Simvastatin 20 mg, Drug: Ezetimibe PlaceboParticipants were instructed to take one ezetimibe placebo tablet and one simvastatin 20-mg tablet orally in the evening every day for six weeks in addition to their daily, oral, open-label, 20-mg simvastatin tablet. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Subject must have diabetes mellitus type 2 (fasting plasma glucose >7 mmol/L [126 mg/dL]) of at least 12 months duration at Visit 3 and must be adequately controlled (glycated hemoglobin [HbA1c] <=9.0%). Subjects must not have had a change in antidiabetic pharmacotherapy [i.e. changes in dosage (with the exception of +/- 10 units of insulin) or addition of new medication] or experience recent history of repeated hypoglycemia or unstable glycemic control within 3 months of Visit (Baseline Visit).
- 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 transluminal coronary intervention (PCTI) 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 have a low-density lipoprotein cholesterol (LDL-C) concentration >=2.6 mmol/L (100 mg/dL) to <=4.1 mmol/L (160 mg/dL) using the Friedewald calculation available 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 and by history has taken 80% of daily evening doses for the 6 weeks prior to Visit 3 (Baseline Visit).
Key exclusion criteria (21 listed)
- Subjects whose body mass index (BMI = weight[kg]/height[m]2) is >=35 kg/m2 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 10 mg1 x 10-mg tablet, provided as blinded study treatment | Drug | Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg |
| Simvastatin 20 mg1 x 20-mg tablet, provided as open-label study treatment | Drug | Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg, Ezetimibe Placebo + Simvastatin 40 mg |
| Ezetimibe Placebo1 tablet matching ezetimibe 10-mg tablet, provided as blinded study treatment | Drug | Ezetimibe Placebo + Simvastatin 40 mg |
| Simvastatin 20 mg1 x 20-mg tablet, provided as blinded study treatment | Drug | Ezetimibe Placebo + Simvastatin 40 mg |
| Simvastatin Placebo1 tablet matching 20-mg simvastatin tablet, provided as blinded study treatment | Drug | Ezetimibe 10 mg + Simvastatin Placebo + Simvastatin 20 mg |
Primary outcome
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint, After 6 Weeks of Treatment
Time frame: 6 weeks of treatment (from Baseline to Endpoint)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 20492655Bardini G, Giorda CB, Pontiroli AE, Le Grazie C, Rotella CM. Ezetimibe + simvastatin versus doubling the dose of simvastatin in high cardiovascular risk diabetics: a multicenter, randomized trial (the LEAD study). Cardiovasc Diabetol. 2010 May 21;9:20. doi: 10.1186/1475-2840-9-20.
- 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.
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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 3 study testing Ezetimibe 10 mg and Simvastatin 20 mg in people with Hypercholesterolemia and Diabetes Mellitus, Type 2, 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 21 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 9 Feb 2022. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 9 Mar 2010). 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?
Percent Change in Low-Density Lipoprotein Cholesterol (LDL-C) From Baseline to Endpoint, After 6 Weeks of Treatment (time frame: 6 weeks of treatment (from Baseline to Endpoint)). 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 NCT00423488, 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 9 Feb 2022.