HypercholesterolemiaPhase 4NCT00202904
Effectiveness and Safety of Ezetimibe Added to Atorvastatin in Patients With High Cholesterol and Coronary Heart Disease (Study P03740)
A Phase 4 study testing ezetimibe in people with Hypercholesterolemia and Coronary Heart Disease, run by Organon and Co.
Trial summary
This is a multicenter, randomized, parallel group, placebo controlled study designed to evaluate the efficacy, safety, and tolerability of ezetimibe added to ongoing atorvastatin therapy compared with ongoing atorvastatin treatment alone. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Hypercholesterolemia, Coronary Heart Disease
- What is being tested?
- ezetimibe
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 81 participants
- Where
- No sites listed yet
- Study dates
- May 2005to Oct 2006
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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 demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- 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) using the Friedewald calculation available at the time of randomization (Baseline Visit).
- Subjects must have triglyceride concentrations of <3.99 mmol/L (350 mg/dL) at Visit 3 (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)
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- History of myocardial infarction
- History of percutaneous coronary intervention (primarily percutaneous coronary transluminal angioplasty (PCTA) with or without stent placement)
- Symptomatic peripheral vascular disease (claudication)
- Documented history of unstable angina or non-Q wave myocardial infarction.
- Subject must be currently taking atorvastatin 10 mg daily and by history has taken 80% of daily doses for the preceding 6 weeks prior to Visit 3 (Baseline Visit).
- 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 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 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 current cholesterol-lowering diet and their current exercise regimen for the duration of the study.
Who cannot join
- Subjects whose body mass index (BMI=weight [kg]/height2[m]) is >=30 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.
- Subjects who have not observed the designated washout periods for any of the prohibited medications.
- Subjects who have the following medical conditions:
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- Congestive heart failure defined by New York Heart Association (NYHA) as Class III or IV.
- 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.
- Uncontrolled hypertension (treated or untreated) with systolic blood pressure >160 mmHg or diastolic >100 mmHg 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 (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 thyroid-stimulating hormone (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 are on any of the following concomitant medications:
- Medications that are potent inhibitors of CYP3A4, including cyclosporine, systemic itraconazole, fluconazole, and ketoconazole, erythromycin or clarithromycin, nefazodone, mibefradil, protease inhibitors and large amounts of grapefruit juice (>1 quart/day).
- Lipid-lowering agent: niacin (>200 mg/day) and resins taken within 5 weeks, fibric acid derivatives taken within 8 weeks, and probucol taken within one year prior to Visit 3 (Baseline Visit).
- Over the counter lipid lowering agents such as fish oils, garlic and cholestin taken within 5 weeks prior to Visit 3 (Baseline Visit).
- 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 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.
- Subjects who are currently using orlistat or sibutramine.
About this study
Official title: A Multicenter, Randomized, Parallel Groups, Placebo-Controlled Study Comparing the Efficacy, Safety, and Tolerability of the Daily Co-Administration of Ezetimibe 10 mg or Ezetimibe Placebo to Ongoing Treatment With Atorvastatin 10 mg in Subjects With Primary Hypercholesterolemia and Coronary Heart Disease
This is a multicenter, randomized, parallel group, placebo controlled study designed to evaluate the efficacy, safety, and tolerability of ezetimibe added to ongoing atorvastatin therapy compared with ongoing atorvastatin treatment alone. This study will involve subjects with primary hypercholesterolemia and coronary heart disease (CHD) who are currently being treated with atorvastatin and who would benefit from additional reduction in low-density lipoprotein cholesterol (LDL-C).
Read the detailed description
This multicenter, randomized, parallel groups, placebo-study is designed for subjects with primary hypercholesterolemia [plasma LDL-C concentrations between >= 2.6 mmol/L (100 mg/dL) to <= 4.1 mmol/L (160 mg/dL) and triglyceride concentrations of < 3.99 mmol/L (350 mg/dL) and coronary heart disease who are currently being treated with atorvastatin 10 mg and would benefit from additional reduction in LDL-C.
This study will assess whether the daily co-administration of ezetimibe 10 mg to ongoing treatment with atorvastatin 10 mg will be more effective than treatment with atorvastatin 10 mg alone in further reducing LDL-C concentrations and in achieving LDL-C target goal as defined by the ESC or National Cholesterol Education Program (NCEP) guidelines at the time of database lock.
The primary objective is to compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus ezetimibe placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint after 6 weeks of treatment.
The secondary objective is to compare the efficacy of ezetimibe 10 mg added to ongoing treatment with atorvastatin 10 mg daily versus ezetimibe placebo added to ongoing treatment with atorvastatin 10 mg daily after 6 weeks of treatment with respect to:
- The percentage of subjects who achieve the target LDL-C goal as defined by the ESC or NCEP guidelines at the time of database lock.
- Change in the concentrations of total cholesterol, HDL-C and triglycerides.
- Safety and tolerability. Approximately 200 subjects will be enrolled into the study to insure that at least 160 subjects complete the study. Each site will enroll approximately 20 subjects for a total of approximately 200 subjects.
The duration of the study for each subject will be approximately 7 weeks. Each subject will be scheduled for 3-4 study visits. Visits 1 and 2 are screening visits; these visits may be combined. At Visit 3, those subjects who meet the enrollment criteria will be randomized to one of two treatment groups: ezetimibe 10 mg or ezetimibe placebo to be taken with ongoing open-label atorvastatin 10 mg/day. Randomization will be stratified based on the LDL-C level at Visit 3: < 3.3 mmol/L (130 mg/dL) or >= 3.3 mmol/L (130 mg/dL). Subjects will be treated for 6 weeks and then return for a final visit, Visit 4.
- Conditions
- Hypercholesterolemia, Coronary Heart Disease
- Being tested
- ezetimibe, placebo
- Keywords
- ezetimibe, atorvastatin, hypercholesterolemia, coronary heart disease
- 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.
ezetimibeDrug
Also called Zetia, SCH 58235
ezetimibe 10 mg tablets, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks
placeboDrug
placebo tablets matched to ezetimibe, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: ezetimibe |
| Arm 2 | Active comparator | Not described Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint
Measured: after 6 weeks of treatment
Secondary outcomes (3)
To compare the percentage of subjects who achieve target LDL-C goal (as defined by the ESC or NCEP guidelines at the time of database lock) with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Measured: after 6 weeks of treatment
To compare the change in concentrations of total cholesterol, HDL-C and triglycerides with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Measured: after 6 weeks of treatment
To compare the safety and tolerability of ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Measured: after 6 weeks of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startMay 2005
- Primary completionOct 2006
- Study completionOct 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 81 participants (actual)
Sponsor and investigators
- Lead sponsor
- Organon and Co
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00202904
- Sponsor's protocol ID
- P03740
- Status last verified
- Feb 2022
- First submitted
- 13 Sep 2005
- Last updated
- 16 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Parallel Groups, Placebo-Controlled Study Comparing the Efficacy, Safety, and Tolerability of the Daily Co-Administration of Ezetimibe 10 mg or Ezetimibe Placebo to Ongoing Treatment With Atorvastatin 10 mg in Subjects With Primary Hypercholesterolemia and Coronary Heart Disease
- ClinicalTrials.gov ID
- NCT00202904
- Acronym / sponsor ID
- P03740
- Conditions
- Hypercholesterolemia, Coronary Heart Disease
- Keywords
- ezetimibe, atorvastatin, hypercholesterolemia, coronary heart disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 81 participants (actual)
- Lead sponsor
- Organon and CoIndustry (pharma, biotech, devices)
- Study start
- May 2005
- Primary completion
- Oct 2006 (actual)
- Study completion
- Oct 2006 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multicenter, randomized, parallel group, placebo controlled study designed to evaluate the efficacy, safety, and tolerability of ezetimibe added to ongoing atorvastatin therapy compared with ongoing atorvastatin treatment alone. This study will involve subjects with primary hypercholesterolemia and coronary heart disease (CHD) who are currently being treated with atorvastatin and who would benefit from additional reduction in low-density lipoprotein cholesterol (LDL-C).
Detailed description
This multicenter, randomized, parallel groups, placebo-study is designed for subjects with primary hypercholesterolemia [plasma LDL-C concentrations between >= 2.6 mmol/L (100 mg/dL) to <= 4.1 mmol/L (160 mg/dL) and triglyceride concentrations of < 3.99 mmol/L (350 mg/dL) and coronary heart disease who are currently being treated with atorvastatin 10 mg and would benefit from additional reduction in LDL-C.
This study will assess whether the daily co-administration of ezetimibe 10 mg to ongoing treatment with atorvastatin 10 mg will be more effective than treatment with atorvastatin 10 mg alone in further reducing LDL-C concentrations and in achieving LDL-C target goal as defined by the ESC or National Cholesterol Education Program (NCEP) guidelines at the time of database lock.
The primary objective is to compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus ezetimibe placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint after 6 weeks of treatment.
The secondary objective is to compare the efficacy of ezetimibe 10 mg added to ongoing treatment with atorvastatin 10 mg daily versus ezetimibe placebo added to ongoing treatment with atorvastatin 10 mg daily after 6 weeks of treatment with respect to:
- The percentage of subjects who achieve the target LDL-C goal as defined by the ESC or NCEP guidelines at the time of database lock.
- Change in the concentrations of total cholesterol, HDL-C and triglycerides.
- Safety and tolerability. Approximately 200 subjects will be enrolled into the study to insure that at least 160 subjects complete the study. Each site will enroll approximately 20 subjects for a total of approximately 200 subjects.
The duration of the study for each subject will be approximately 7 weeks. Each subject will be scheduled for 3-4 study visits. Visits 1 and 2 are screening visits; these visits may be combined. At Visit 3, those subjects who meet the enrollment criteria will be randomized to one of two treatment groups: ezetimibe 10 mg or ezetimibe placebo to be taken with ongoing open-label atorvastatin 10 mg/day. Randomization will be stratified based on the LDL-C level at Visit 3: < 3.3 mmol/L (130 mg/dL) or >= 3.3 mmol/L (130 mg/dL). Subjects will be treated for 6 weeks and then return for a final visit, Visit 4.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: ezetimibe |
| Arm 2 | Active comparator | Drug: placebo |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- 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) using the Friedewald calculation available at the time of randomization (Baseline Visit).
- Subjects must have triglyceride concentrations of <3.99 mmol/L (350 mg/dL) at Visit 3 (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:
Key exclusion criteria (27 listed)
- Subjects whose body mass index (BMI=weight [kg]/height2[m]) is >=30 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.
- Subjects who have not observed the designated washout periods for any of the prohibited medications.
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 |
|---|---|---|
| ezetimibeAlso: Zetia, SCH 58235ezetimibe 10 mg tablets, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks | Drug | Arm 1 |
| placeboplacebo tablets matched to ezetimibe, one tablet taken daily with atorvastatin 10 mg daily for 6 weeks | Drug | Arm 2 |
Primary outcome
To compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint
Time frame: after 6 weeks of treatment
3 secondary outcomes
To compare the percentage of subjects who achieve target LDL-C goal (as defined by the ESC or NCEP guidelines at the time of database lock) with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Time frame: after 6 weeks of treatment
To compare the change in concentrations of total cholesterol, HDL-C and triglycerides with ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Time frame: after 6 weeks of treatment
To compare the safety and tolerability of ezetimibe 10 mg added to atorvastatin 10 mg daily versus placebo added to atorvastatin 10 mg daily
Time frame: after 6 weeks of treatment
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
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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 in people with Hypercholesterolemia and Coronary Heart 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 19 inclusion and 27 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 16 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To compare the efficacy of ezetimibe 10 mg added daily to ongoing treatment with atorvastatin 10 mg versus placebo added daily to ongoing treatment with atorvastatin 10 mg in reducing the concentration of LDL-C at endpoint (time frame: after 6 weeks of treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Feb 2022.