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    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2011-002507-15
    Sponsor's Protocol Code Number:GS-US-259-0116
    National Competent Authority:Czechia - SUKL
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-12-28
    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 ConcernedCzechia - SUKL
    A.2EudraCT number2011-002507-15
    A.3Full title of the trial
    A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of the Effects of Ranolazine on Major Adverse Cardiovascular Events in Subjects with a History of Chronic Angina Who Undergo Percutaneous Coronary Intervention with Incomplete Revascularization
    Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie fáze 3, zkoumající účinky přípravku ranolazin na významné nežádoucí kardiovaskulární příhody u pacientů s chronickou anginou pectoris v anamnéze, kteří absolvují perkutánní koronární intervenci s neúplnou revaskularizací
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A placebo controlled, randomized clinical study to evaluate whether ranolazine can prevent death, heart attacks, or hospitalization for chest pain in patients with a history of chest pain who had a procedure to open up blockages in blood vessels feeding the heart, but still have some blockages left untreated.
    A.4.1Sponsor's protocol code numberGS-US-259-0116
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorGilead Sciences, Inc.
    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 supportGilead Sciences, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationGilead Sciences International Limited
    B.5.2Functional name of contact pointClinical Trials Information
    B.5.3 Address:
    B.5.3.1Street AddressFlowers Building, Granta Park
    B.5.3.2Town/ cityGreat Abington, Cambridge
    B.5.3.3Post codeCB21 6GT
    B.5.3.4CountryUnited Kingdom
    B.5.4Telephone number+442085872210
    B.5.5Fax number+441223897284
    B.5.6E-mailclinical.trials@gilead.com
    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 Ranexa 500 mg prolonged-release tablets
    D.2.1.1.2Name of the Marketing Authorisation holderMenarini International Operations Luxembourg S.A.
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    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.3.4Pharmaceutical form Prolonged-release tablet
    D.3.4.1Specific paediatric formulation No
    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 INNRANOLAZINE
    D.3.9.1CAS number 95635-55-5
    D.3.9.4EV Substance CodeSUB10259MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number500
    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) No
    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 No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    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 No
    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 placeboFilm-coated tablet
    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
    Coronary artery disease
    E.1.1.1Medical condition in easily understood language
    Heart disease
    E.1.1.2Therapeutic area Diseases [C] - Cardiovascular Diseases [C14]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 16.1
    E.1.2Level PT
    E.1.2Classification code 10011078
    E.1.2Term Coronary artery disease
    E.1.2System Organ Class 10007541 - Cardiac disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to evaluate the efficacy of ranolazine as compared with placebo when used as part of standard medical therapy in chronic angina subjects with incomplete
    revascularization post-PCI on the composite of ischemia-driven
    revascularization or ischemia-driven hospitalization without
    revascularization.
    E.2.2Secondary objectives of the trial
    The secondary objectives of this study are to:
    -Evaluate the efficacy of ranolazine as compared with placebo when used
    as part of standard medical therapy in chronic angina subjects with
    incomplete revascularization post-PCI on the incidence of sudden
    cardiac death
    -Evaluate the efficacy of ranolazine as compared with placebo when used
    as part of standard medical therapy in chronic angina subjects with
    incomplete revascularization post-PCI on the incidence of CV death
    -Evaluate the efficacy of ranolazine as compared with placebo when used
    as part of standard medical therapy in chronic angina subjects with
    incomplete revascularization post-PCI on the incidence of MI
    -Assess quality of life (QoL) in the ranolazine group as compared to the
    placebo group at Months 1, 6 and 12
    -Assess the pharmacoeconomic benefit of ranolazine post-PCI
    -Evaluate the tolerability and safety of ranolazine post-PCI
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Integrated Quality of Life Study and Health Economics Sub-Study.
    Date/Version: 15Feb2012
    Health Economics sub-study current planned for US only.
    Quality of Life is planned globally.
    E.3Principal inclusion criteria
    1. Written informed consent
    2. Males and females aged 18 years and older
    3. History of chronic angina defined as at least 2 episodes of anginal pain or discomfort in the chest, jaw, shoulder, back, neck, or arm that is precipitated by exertion or emotional stress and relieved by rest or sublingual nitroglycerin which occurred on at least 2 separate days and at least 14 days prior to PCI (in the case of staged PCI procedures, at least 14 days prior to the first PCI in the series). Subjects may or may not have additional angina episodes within the 14 days prior to their first PCI in the series, as well as anytime prior to Randomization.
    4. PCI for any indication (ACS or non-ACS). For the purposes of stratification at randomization, ACS will be defined as hospitalization for anginal pain or discomfort within the previous 24 hours to their hospitalization with any one (or more) of the following criteria:
    i. Elevated troponin or creatinine kinase-MB (CK-MB) consistent with MI, as reported by local laboratory and measured prior to index PCI
    ii. Electrocardiographic changes (including transient changes)comprising new or presumably new ST segment depression ≥ 0.1 mV (≥ 1 mm), or ST segment elevation ≥ 0.1 mV (≥ 1 mm) in at least 2 contiguous leads, or new or presumably new Left Bundle Branch Block
    5. Randomization within 14 days post-PCI. In case of staged PCI procedures, randomisation has to occur within 14 days of last PCI in the series. The first day of the 14-day randomisation window is the day after the PCI. PCI is defined as an attempt to cross the lesion with a wire.
    6.Post-PCI (post the last PCI for staged procedures) evidence of incomplete revascularization defined as the presence of one or more visually estimated ≥ 50% stenosis in one or more coronary arteries with reference vessel diameter of at least 2.0 mm, whether in the target vessel or in a non-target vessel regardless of the presence or absence of coronary collaterals. In the case of a subject post-CABG, incomplete revascularization is defined as the presence of one or more visually estimated ≥ 50% stenosis in an unbypassed epicardial vessel with a reference diameter ≥ 2.0 mm in diameter, or one or more visually estimated ≥ 50% stenosis in a bypass graft supplying an otherwise unrevascularized myocardial territory.
    7.Clinically stable post-PCI. Subjects randomized in-hospital on day of planned discharge or in clinic are considered stable. Subjects randomized in-hospital prior to day of planned discharge are considered stable if they meet all of the following criteria:
    i.CK-MB < 3 times the upper limit of normal (ULN) at least 3 hours post-PCI, or if ≥ 3 times the ULN with evidence of decreasing CK-MB (decreased by at least 20% from the prior measure), as reported by local laboratory. If CK-MB is not available, a subject must have evidence of normal or decreasing troponin levels (decreased by at least 20% from the prior measure) at least 3 hours post-PCI, as reported by local laboratory.
    ii.Systolic blood pressure ≥ 90 mm Hg and not receiving pressors or inotropes
    iii.No current requirement for an intra-aortic balloon pump (IABP) or any left ventricular assist device
    iv.No current requirement for intravenous (IV) nitroglycerin
    8. Ability and willingness to comply with all study procedures during the course of the study
    9. Females of childbearing potential must have a negative pregnancy test at Screening (unless surgically sterile or post-menopausal) and must agree to use highly effective contraception methods from Screening throughout the duration of study treatment and for 14 days following the last dose of study drug.
    E.4Principal exclusion criteria
    1.Any future planned revascularization (including staged procedures) or possible planned revascularization (ie, planned stress test to assess the imminent need for additional revascularization). Future planned stress tests for purposes of monitoring are permitted but strongly discouraged. If a stress test is performed following Randomization, the test should be performed on the subject’s concurrent medical treatment regimen including all antianginals and study drug. Medications should therefore not be held for the test. Subjects may be enrolled after the last PCI in the staged series or once a decision is made not to perform a follow up PCI, as long as Randomization occurs within 14 days from the last PCI. If a subject has had a stress test post-PCI and prior to Randomization and no further intervention is planned, the subject may be enrolled within 14 days from the last PCI.
    2. Unrevascularized left main coronary artery stenosis ≥ 50%. Subjects with history of CABG to the left coronary system will be considered to have a revascularised left main if at least one graft is patent.
    3. Major complication during or after the index PCI (in the case of staged PCI, the last in the series) including: i. Major bleeding (TIMI Bleeding classification or any bleeding requiring ≥ 2 units of red blood cells) ii. Coronary perforation requiring treatment iii. Procedural complication requiring surgery (including CABG or peripheral vascular surgery)
    4. Stroke within 90 days prior to Randomization, or any history of stroke with permanent major neurologic disability (eg, aphasia or significant motor dysfunction)
    5. Cardiogenic shock within 90 days prior to Randomization (transient decreases in the blood pressure without clinical sequelae are not considered to be cardiogenic shock)
    6. New York Heart Association (NYHA) Class III or IV heart failure 7. Severe renal insufficiency as assessed by an estimated GFR < 30 mL/min/1.73m2 using the 4 variable modification of diet in renal disease (MDRD) equation, per local laboratory (based on the last available measurement prior to Randomization, collected within 1 month prior to the index PCI [in the case of staged PCI, the last in the series])
    8. Liver cirrhosis
    9. Use of Class Ia, Ic, or Class III antiarrhythmics, except for amiodarone
    10. Current treatment with strong inhibitors of CYP3A
    11. Current treatment with CYP3A4 inducers or P-gp inducers 12. Subjects taking > 20 mg simvastatin daily or > 40 mg lovastatin daily who cannot reduce the dose to 20 mg once daily for simvastatin or 40 mg once daily for lovastatin, or who cannot switch to another statin
    13. Subjects taking greater than a total of 1000 mg daily of metformin who cannot reduce the dose to a maximum total of 1000 mg daily (additional anti-diabetic medications may be added as clinically indicated to allow subjects to decrease their metformin dose and maintain glycemic control)
    14.Previous treatment with ranolazine for > 7 consecutive days within 30 days prior to Randomization, or known hypersensitivity or intolerance to ranolazine or to any of the excipients
    15. Participation in another investigational drug or device study within 30 days prior to Randomization (participation in registries is allowed)
    16. Women who are pregnant or breast feeding
    17. Non-CAD comorbid conditions (e.g. advanced malignancy, severe aortic stenosis) which are likely to result in death within 2 years of Randomization
    18. Any condition that in the opinion of the investigator would preclude compliance with the study protocol.
    E.5 End points
    E.5.1Primary end point(s)
    The primary efficacy endpoint of this study is time form randomization to the first occurence of ischemia-driven revascularization or ischemia-driven hospitalization without
    revascularization.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoints will be adjudicated throughout the study by the Clinical Events Committee.
    E.5.2Secondary end point(s)
    Secondary endpoints will include:
    • Time from randomization to sudden cardiac death
    • Time from randomization to CV death
    • Time from randomization to MI
    Additional secondary endpoints will include:
    • Evaluation of QoL and health related costs, as detailed in the Integrated QoL Study and Health Economics Sub-Study
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary points will be adjudicated throughout the study by the Clinical Events Committee.
    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 No
    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 No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    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.8.2.4Number of treatment arms in the trial2
    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 concerned7
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA90
    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 No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Canada
    Denmark
    France
    Italy
    Austria
    Netherlands
    Sweden
    Czech Republic
    Germany
    Spain
    Israel
    Poland
    Russian Federation
    United Kingdom
    United States
    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
    The study will continue until at least 1 year post-randomization followup
    has been achieved for all subjects and at least 720 adjudicated first
    post-randomization primary endpoint events (ischemia-driven
    revascularization or ischemia-driven hospitalization without
    revascularization) have been observed.
    The end of the study will be reached when the last subject enrolled has
    completed their final End of Treatment visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 1325
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1325
    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 No
    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 state140
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1175
    F.4.2.2In the whole clinical trial 2600
    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)
    Subjects should continue concomitant antianginal medications and should restart any medications discontinued during the screening period after completion of all study procedures under the care of their primary 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 Decision2012-01-13
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-01-18
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-02-03
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