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    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   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:2011-001516-54
    Sponsor's Protocol Code Number:GS-US-259-0103
    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:2011-07-28
    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 ConcernedUK - MHRA
    A.2EudraCT number2011-001516-54
    A.3Full title of the trial
    A Phase 4, Randomized, Double-Blind, Placebo-Controlled, Cross-over Trial to Evaluate the Effects of Ranolazine on Myocardial Perfusion Assessed by Serial Quantitative Exercise SPECT Imaging.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A randomized, double-blind, placebo-controlled, cross-over trial looking at the effects of ranolazine on blood flow in the heart as assessed by nuclear imaging.
    A.4.1Sponsor's protocol code numberGS-US-259-0103
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01221272
    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+441223897 496
    B.5.5Fax number+441223897 284
    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 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.3.4Pharmaceutical 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.3.9.2Current sponsor codeGS-9668
    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 14.1
    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 objective of this study is to evaluate the effect of ranolazine 1000 mg administered twice daily compared to placebo on exercise-induced myocardial perfusion defect size (PDS) and total perfusion deficit (TPD), assessed by gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) in subjects with documented exercise-induced myocardial ischemia at baseline.
    E.2.2Secondary objectives of the trial
    Not applicable.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Written informed consent
    2. Males and females aged ≥ 18 years
    3. Able to perform exercise stress testing (either a treadmill test or upright cycle ergometry)
    4. One of the following:
    - An exercise SPECT MPI study (stress and rest) performed not more than 12 weeks prior to Screening, OR
    - An exercise SPECT MPI study (stress and rest) performed during screening (after consultation with the Medical Monitor and after informed consent has been obtained) on subjects who have a high likelihood of qualifying in the opinion of the Principal Investigator
    5. At least 10% reversible myocardial ischemia on the qualifying exercise SPECT MPI study as confirmed by the core nuclear laboratory
    6. Stable antianginal medical therapy, excluding short-acting nitroglycerin. The doses of any antianginal medications (other than short-acting nitroglycerin) should not have significantly increased since the qualifying scans were conducted.
    7. Females of child-bearing potential must agree to utilize 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
    General
    1. Unwilling or unable to provide informed consent
    2. Body Mass Index (BMI) ≥ 38 kg/m2 (may be up to 40 kg/m2 after consultation with the Medical Monitor)
    3. Females who are breastfeeding
    4. Positive serum pregnancy test (female of child-bearing potential)
    5. Inability to exercise or exercise limitation due to other co-morbidities that may interfere with ability to perform required exercise SPECT MPI study (eg, significant chronic lung disease, prior hospitalization for acute exacerbation of chronic lung disease or home oxygen use or chronic oral steroid therapy that can limit exercise capacity)
    6. Any absolute contraindications to exercise stress testing
    7. Any other conditions that, in the opinion of the investigator, are likely to prevent compliance with the study protocol or pose a safety concern if the subject participates in the trial
    8. Participation in another trial of an investigational drug or device within 30 days (or 5 half-lives, whichever is greater) prior to Screening Criteria Related to Medical History
    9. Left bundle branch block
    10. Automated implantable defibrillator
    11. Pacemaker (selected subjects with permanent pacemakers who have an intact intrinsic sinus mechanism may be included after consultation with the Medical Monitor)
    12. Acute myocardial infarction within 60 days prior to Screening or at any time after the qualifying exercise SPECT MPI study, or MI undergoing staged intervention during the duration of this trial
    13. Resting LV ejection fraction < 30%
    14. Intervening coronary revascularization between the time of the qualifying exercise SPECT MPI study and Randomization
    15. Anticipated coronary revascularization during the trial period
    16. Unstable angina within 30 days prior to Screening or at any time after the qualifying exercise SPECT MPI study
    17. Coronary artery bypass graft (CABG) surgery within 60 days prior to Screening or at any time after the qualifying exercise SPECT MPI study, or percutaneous coronary intervention (PCI) within 30 days prior to Screening or at any time after the qualifying exercise SPECT MPI study
    18. Cerebrovascular Attack (CVA) or Transient Ischemic Attack (TIA) within 90 days prior to Screening
    19. History of serious arrhythmias
    20. Currently in atrial fibrillation or atrial flutter
    21. QTc interval > 500 milliseconds
    22. Diagnosed as having New York Heart Association Class III or IV heart failure
    23. Prior heart transplant
    24. Clinically significant valvular or congenital heart disease
    25. Severe pulmonary hypertension
    26. Clinically significant hepatic impairment
    27. Creatinine clearance < 30 mL/min according to the Cockcroft-Gault formula
    Male: ((140 – age in years) × (wt in kg))/ (72 × (serum creatinine in mg/dL)) = CrCl (mL/min)
    Female: ((140 – age in years) × (wt in kg))/(72 × (serum creatinine in mg/dL)) × 0.85 = CrCl (mL/min)
    Criteria Related to Medications
    28. Current or prior treatment with ranolazine
    29. Current treatment with Class Ia, Ic or III antiarrhythmic medications, except amiodarone at a stable dose for at least 12 weeks prior to the qualifying scan
    30. Current treatment with strong inhibitors of CYP3A
    31. Current treatment with CYP3A and P-gp inducers
    32. Current treatment with CYP3A4 substrates with a narrow therapeutic range
    (eg, cyclosporine, tacrolimus, sirolimus)
    33. Subjects taking simvastatin who cannot reduce the dose to 20 mg once daily or who cannot switch to another statin
    34. 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)
    E.5 End points
    E.5.1Primary end point(s)
    The co-primary efficacy endpoints for this study are:
    • Effect of ranolazine (versus placebo) on exercise-induced PDS
    • Effect of ranolazine (versus placebo) on exercise-induced TPD
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 15 and 30.
    E.5.2Secondary end point(s)
    Secondary Endpoints:
    1. Effect of ranolazine (versus placebo) on the following SPECT MPI variables:
    a. Exercise-induced perfusion defect severity
    b. Exercise-induced reversible PDS and TPD
    E.5.2.1Timepoint(s) of evaluation of this end point
    Day 15 and 30.
    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 Yes
    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) 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 No
    E.8.1.6Cross over Yes
    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 concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA25
    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
    Canada
    Czech Republic
    Finland
    Israel
    Italy
    Poland
    Singapore
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    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
    Two week safety follow up call after the last subject's last visit
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years0
    E.8.9.1In the Member State concerned months8
    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 months0
    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: 107
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 107
    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 state12
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 69
    F.4.2.2In the whole clinical trial 214
    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 Decision2011-09-12
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-11-24
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2012-09-27
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