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    The EU Clinical Trials Register currently displays   36117   clinical trials with a EudraCT protocol, of which   5940   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2005-001059-39
    Sponsor's Protocol Code Number:P 04103
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2005-09-30
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2005-001059-39
    A.3Full title of the trial
    A Multicenter, Double-Blind, Randomized Study to Establish the Clinical Benefit and Safety of Vytorin (Ezetimibe/Simvastatin Tablet) vs Simvastatin Monotherapy in High-Risk Subjects Presenting with Acute Coronary Syndrome (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial)
    A.3.2Name or abbreviated title of the trial where available
    IMPROVE IT
    A.4.1Sponsor's protocol code numberP 04103
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorSchering-Plough Research Institute
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Information not present in EudraCT
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameInegy
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNEzetimibe/Simvastatin
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10/40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Information not present in EudraCT
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameZocor
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNSimvastatin
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number40
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Primary Hyperlipidermia
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 8
    E.1.2Level LLT
    E.1.2Classification code 10016205
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the clinical benefit of Ezetimibe/Simvastatin Combination 10/40 (single tablet) compared with Simvastatin 40mg in stablilized acute coronary syndrome (ACS) subjects. Clinical benefit will be defined as the reduction in the risk of the occurrence of the composite endpoint of CV death, major coronary events, and non-fatal stroke. Major coronary events include non-fatal MI, documented unstable angina that requires admission into a hospital and all coronary revascularization with either PCI or CABG occuring at least 30 days after randomization. Only revasculatiztion events that occur after the first 30 days of treatment will be considered as Clinical Endpoint events, in order to focus on events that can be expected to be affected by treatment and are unrelated to the initial ACS event.
    E.2.2Secondary objectives of the trial
    a. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of death due to all causes, major coronary events and non-fatal stroke.
    b. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of death due to coronary heart disease, non fatal MI, and urgent coronary revascularization with either PCI or CABG occurring at least 30 days after randomization.
    c. Evaluate the clinical benefit of Ezetimibe/Simvastatin Combination compared to Simvastatin on the occurance of the composite endpoint of CV death, non fatal MI, Unstable angna requiring hospitalization, all and revascularization at least 30 days after randomization and Non-fatal stroke
    E.2.3Trial contains a sub-study Information not present in EudraCT
    E.3Principal inclusion criteria
    High-risk ACS NSTE-ACS & STEMI subjects meeting the following conditions:
    1. NSTE-ACS subjects meeting the following definition:
    a. Clinically stable NSTE-ACS subjects participating in EARLY ACS Study (P03684) that do not go on to have CABG will be eligible if enrolled within 10 days of their hospitalization.
    b. Clinically stable NSTE-ACS subjects not participating in EARLY ACS study who meet the following criteria will be eligible to enroll within 10 days of their hospitalization: Experience symptoms of cardiac ischemia at rest lasting at least 10 min within 24 hrs of hospitalization, at least 50yrs of age, and have 1 of the following: ECG changes in at least 2 contiguous leads characterized by either ST depression or transient ST elevation, elevation in cardiac enzymes, DM, History of MI, History of PAD, History of CVD, History of CABG at least 3 yrs prior,or multivessel documented CAD.
    2. Clinically stable STEMI subjects maybe enrolled within 10 days of their hospitalization if they meet the following criteria: Experience symptoms of cardiac ischemia at rest with at least one episode lasting at least 30 minutes in conjunction with hospitalization and have ECG changes in at least 2 contiguous leads characterized by ST elevation or Qwaves or LBBB, have elevation in cardiac enzymes and the presences of anterior infarction or at least 50yrs of age.
    3. LDL-C criteria: Lipid therapy naïve subjects LDL-C must be at least 1.3 mmol/L and equal to 3.0 mmol/L, Subjects on chronic prescription lipi lowering therapy LDL-C must be at least 1.3 and less than or equal to 2.6 mmol/L.
    4. Fasting Plasma Triglyceride must be less than or equal to 4.0 mmol/L.
    5.Subjects, in whom PCI is planned as management, should be randomized folllowing PCI and within the 10 days period after initial hospitalization for qualifying event. Staged PCI is allowed but needs to be completed within 30 days of randomization.
    E.4Principal exclusion criteria
    1. Subject who is clinically unstable. A subject is considered clinically unstable if he/she displays any of the following spontaneous events for 24 hours prior to Screening-Randomization:
    a. Hemodynamic events: Hypotension, Pulmonary edema/CHF, Acute mitral regurgitation, Acute ventricular septal defect.
    b. Ischemic events: stroke, recurrent sx of cardiac ischemica.
    c Arrhythmic events: Ventricular fibrillation, Sustained ventricular tachycardia, complete heart block, High grade second degree heart block
    2. Subject requiring the following concomitant medications that can not be discontinued: statins, ezetimibe, fusidic acid, torcetrapib within 1 year prior to randomization, cyclosporine, diltiazem, danazol, amiodarone, verapamil, niacin, fibrates as concomitant medication or any of the potent CYP3A4 inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin and Telithromycin, HIV protease inhibitors, nedazodone
    3. Pregnant or lactating woman, or intenting to become pregnant
    4. Active liver disease or persistent unexplained serum transaminase elevation
    5. History of alcohol or drug abuse,
    6. History of intolerance or hypersensitivity to statin or ezetimibe
    7. Discontinuation of existing lipid lowering regimen poses a risk to the subject
    8. Subject is receiving statin therapy with an LDL-C lowering potency greater than simvastatin 40mg
    9. Prior enrollment in this current study under Protocol P04103
    10. Subjects who undergo CABG in response to qualifying event.
    11. Patients with calculated creatinine clearance (CrCl) <30 mL/mit or dialysis within 30 days.
    12. Subjects participating in clinical research of approval therapy being administered according to the therapy's label use are NOT to be excluded.

    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint will be the time from randomization until the first occurrence of one of the following: CV death, major coronary event (non-fatal MI, documented unstable angina that requires admission into a hospital, all coronary revascularization with either PCI or CABG occuring at least 30 days after randomization), or non-fatal stroke.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Information not present in EudraCT
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    simvastatin
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.5The trial involves multiple Member States Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial has a data monitoring committee Information not present in EudraCT
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The planned termination of the study will occur after all 10,000 subjects have been followed for a minimum of 2.5 years and a primary endpoint event has been documented in at least 2955 subjects. if at least 2955 subjects do not have at least one documented primary endpoint event with 2.5 years of the completion of enrollment, the study will continue until this number of events has accumulated. It is anticipated that the whole study duration will be approximately 5 years.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years5
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Information not present in EudraCT
    F.3.3.1Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2005-09-30. Yes
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state136
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 4000
    F.4.2.2In the whole clinical trial 10000
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2005-09-21
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2005-12-20
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2014-09-18
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