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    Summary
    EudraCT Number:2008-005546-23
    Sponsor's Protocol Code Number:Protocol version 1.4.2
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2009-06-04
    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 ConcernedUK - MHRA
    A.2EudraCT number2008-005546-23
    A.3Full title of the trial
    The Insulin Resistance Intervention after Stroke Trial A randomized, placebo-controlled trial of pioglitazone, compared with placebo, for prevention of stroke and myocardial infarction after ischemic stroke and transient ischemic attack
    A.3.2Name or abbreviated title of the trial where available
    The Insulin Resistance Intervention after Stroke (IRIS) trial
    A.4.1Sponsor's protocol code numberProtocol version 1.4.2
    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 SponsorYale University School of Medicine
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    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 Yes
    D.2.1.1.1Trade name Actos
    D.2.1.1.2Name of the Marketing Authorisation holderTakeda Global Research and Development Centre
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    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 namePioglitazone (Actos)
    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 INNpioglitazone
    D.3.9.1CAS number 111025-46-8
    D.3.9.3Other descriptive nameActos
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number15 to 45
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Insulin resistance in patients who have had a stroke or transient ischaemic attack
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine if pioglitazone (a drug to treat insulin resistance), compared to placebo (a dummy medication), will reduce the overall risk for fatal or non-fatal stroke or fatal or non-fatal myocardial infarction (MI, commonly known as 'heart attack') among non-diabetic men and women aged 40 years or older with insulin resistance, who have experienced a recent stroke or transient ischaemic attack (a TIA, sometimes termed a 'mini-stroke). We hypothesize that, among non-diabetics with insulin resistance, pioglitazone will reduce the rate of occurrence of any main outcome (fatal or non-fatal stroke or MI) within four years from 27% to 22%.
    E.2.2Secondary objectives of the trial
    1. To determine if pioglitazone, compared to placebo, will reduce the risk for stroke alone. We hypothesize that pioglitazone will reduce the rate of occurrence of fatal or non-fatal stroke. 2. To determine if pioglitazone, compared to placebo, will reduce the risk for acute MI ('heart attack') or unstable angina (heart related chest pain). Unstable angina is an important clinical event because it identifies individuals at high risk for MI who urgent medical intervention to diagnose and treat their condition. We hypothesize that pioglitazone will reduce the overall rate of occurrence of acute MI and unstable angina. 3. To determine if pioglitazone, compared to placebo, is effective in preventing progression to overt diabetes.Insulin resistance is the principal risk factor for type II diabetes. We hypothesize that pioglitazone, by sensitizing cells to insulin’s action, will prevent progression to diabetes. 4. To determine if pioglitazone, compared to placebo, will reduce the r
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion Criteria a. Age 40 years or greater at the time of randomization. b. Ischemic stroke or TIA no less than 14 days and no more than 6 months before randomization c. Documentation of insulin resistance as defined by a value over 3.0 on the Homeostasis Model Assessment of insulin sensitivity (HOMA). d. Both ability and willingness to provide informed consent. e. Presence of none of the exclusion criteria.
    E.4Principal exclusion criteria
    Permanent Exclusions a. Severely disabling stroke as indicated by an inability to participate in scheduled follow-up activities. b. Persons whose ischemic stroke or TIA was related to structural cardiac lesion, significant head trauma, proximal arterial dissection or medical instrumentation. c. Diabetes mellitus as defined by recent use of medication for diabetes as an out-patient (*see note below) or two fasting plasma blood sugars > 126 mg/dL. d. HgbA1c >= 7.0%. e. Irreversible medical conditions likely to affect short-term survival or ability to participate in the study protocol. These include: • Cancer or other chronic disease with poor prognosis (predicted survival of less than four years). • Severe neurologic or psychiatric disease that would complicate the evaluation of study outcomes (e.g., dementia or schizophrenia). f. History of intolerance to any thiazolidinedione. g. Pregnancy or desire to become pregnant. h. Oral contraceptive use. i. Ongoing use of oral corticosteroids. j. History of heart failure k. Active liver disease as defined by known liver disease accompanied by cirrhosis, significant cholestasis, portal hypertension, hepatic encephalopathy, hepatic synthetic dysfunction, or expected significant loss of liver function over the course of the study. l. History of bladder cancer. m. Current participation in a conflicting clinical trial. A conflicting clinical trial is defined as a trial with any of following: • Intervention that is known to affect the incidence of stroke or myocardial infarction. • Intervention that is an experimental drug. • Outcome that includes stroke or myocardial infarction. • Exclusion for participation in another trial. Temporary Exclusions Persons with temporary exclusions may be enrolled as soon as the exclusion has resolved. a. ALT >2.5 times the upper limit of normal. b. Hemoglobin <8.5 g/dl. c. Moderate or severe pitting edema of the feet or legs (IRIS grade 3 or 4). d. Carotid surgery or carotid stenting procedure scheduled (delay randomization until 2 weeks following procedure). *Patients who have taken a medication to treat diabetes in the prior 3 months as an out-patient will not be eligible for participation. However, a patient who has recently taken a diabetes medication while hospitalized or for a reason other than diabetes (e.g., for impaired glucose tolerance), may be tested for eligibility after at least 7 days off the medication.
    E.5 End points
    E.5.1Primary end point(s)
    Rate of occurrence of fatal or non-fatal stroke or MI (i.e. % of patients in whom one or more of the events occur)
    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 No
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    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) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    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.8.4.1Number of sites anticipated in Member State concerned40
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA80
    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 Yes
    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
    Last patient, last visit
    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 months3
    E.8.9.1In the Member State concerned days22
    E.8.9.2In all countries concerned by the trial years10
    E.8.9.2In all countries concerned by the trial months4
    E.8.9.2In all countries concerned by the trial days29
    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 Yes
    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 2009-06-04. Yes
    F.3.3.2Women of child-bearing potential using contraception Yes
    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 state500
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1000
    F.4.2.2In the whole clinical trial 3936
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    This is a non-commercial study and there are no plans for ongoing provision of pioglitazone to study participants at end of study. Any further prescription would have to be at discretion of treating physician.
    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 Decision2009-06-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2009-06-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-09-02
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