Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   40109   clinical trials with a EudraCT protocol, of which   6567   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).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-001795-30
    Sponsor's Protocol Code Number:DU176b-C-E314
    National Competent Authority:Denmark - DHMA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-10-19
    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 ConcernedDenmark - DHMA
    A.2EudraCT number2016-001795-30
    A.3Full title of the trial
    Evaluation of Edoxaban in Anticoagulant Naïve Patients with Non-Valvular Atrial Fibrillation (NVAF) and high Creatinine Clearance
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Evaluation of Edoxaban in Anticoagulant Naïve patients with normal renal function who are suffering from abnormal and irregular, often rapid heart rate defined as Atrial Fibrillation with no evidence of moderate or severe damage of the heart valves.
    A.4.1Sponsor's protocol code numberDU176b-C-E314
    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 SponsorDaiichi Sankyo, 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 supportDaiichi Sankyo, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDaiichi Sankyo, Inc.
    B.5.2Functional name of contact pointClinical Trial Information Contact
    B.5.3 Address:
    B.5.3.1Street Address399 Thornall Street
    B.5.3.2Town/ cityEdison
    B.5.3.3Post codeNJ 08837
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1 732 590 5000
    B.5.5Fax number+1 732 906-5690
    B.5.6E-maileu_cta@dsi.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 No
    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 nameDU176b
    D.3.4Pharmaceutical form Film-coated 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 INNEDOXABAN (as anhydrous free form)
    D.3.9.1CAS number 480449-71-6
    D.3.9.3Other descriptive nameEDOXABAN TOSYLATE MONOHYDRATE
    D.3.9.4EV Substance CodeSUB182369
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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.IMP: 2
    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 No
    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 nameDU176b
    D.3.4Pharmaceutical form Film-coated 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 INNEDOXABAN (as anhydrous free form)
    D.3.9.1CAS number 480449-71-6
    D.3.9.3Other descriptive nameEDOXABAN TOSYLATE MONOHYDRATE
    D.3.9.4EV Substance CodeSUB182369
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    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.IMP: 3
    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 No
    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 nameDU176b
    D.3.4Pharmaceutical form Film-coated 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 INNEDOXABAN (as anhydrous free form)
    D.3.9.1CAS number 480449-71-6
    D.3.9.3Other descriptive nameEDOXABAN TOSYLATE MONOHYDRATE
    D.3.9.4EV Substance CodeSUB182369
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number60
    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
    Non-Valvular Atrial Fibrillation (NVAF)
    E.1.1.1Medical condition in easily understood language
    Abnormal and irregular, often rapid heart rate with no evidence of moderate or severe damage of the heart valves
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10003658
    E.1.2Term Atrial fibrillation
    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 is to compare the exposure (based on average concentration at steady state (Cav), minimum concentration in plasma (Cmin), and anti-factor Xa [anti-FXa]) of edoxaban 75 mg once daily (QD) dose to edoxaban 60 mg QD dose in NVAF anticoagulant-naïve patients with CHADS2 score of ≥ 2 and CrCL > 100 mL/min (as calculated by the Cockcroft-Gault formula) treated for up to 12 months.
    E.2.2Secondary objectives of the trial
    -Provide an assessment of exposure based on a validated anti-FXa assay using edoxaban calibrators and controls and edoxaban concentration based on liquid chromatography/tandem mass spectrometry;
    -Provide an overall assessment of the patients’ coagulation state based on the PD biomarkers: intrinsic FX, prothrombin time (PT) and activated partial thromboplastin time ( aPTT);
    -Investigate the relationship between exposure Proprietary and Confidential
    4 (anti-FXa activity, edoxaban concentrations) and PD biomarkers (intrinsic FX, PT, aPTT).
    -Evaluate stroke/transient ischemic attack (TIA) and systemic embolic events (SEE);
    -Evaluate the net clinical outcome (composite of stroke/TIA, SEE, myocardial infarction (MI), cardiovascular death, major bleeding);
    -Evaluate the incidence of major (including intracranial) and Clinically Relevant Non-Major [CRNM]) bleeding;
    -Evaluate the incidence of stroke/ TIA and SEE excluding haemorrhagic stroke.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Male or female patients older than the minimum legal adult age (country specific) who have signed an informed consent form for the study;
    2. History of non-valvular AF documented by any electrical tracing (routine 12-lead electrocardiogram [ECG], Holter monitor [continuous ECG recording] rhythm strip, intracardiac electrogram, or pacemaker [PM] or implantable cardiac defibrillator [ICD] interrogation) within the prior 12 months and for which anticoagulation therapy is indicated and planned for the duration of the study;
    3. Patient’s with CrCL > 100 mL/min as measured by the Cockcroft-Gault formula.
    4. Patient has a CHADS2 score of ≥ 2.
    5. Patient’s weight is > 60 Kg.
    6. Patient is naïve to anticoagulant therapy (defined as having received no dose of any oral anticoagulant (VKAs) or direct oral anticoagulant (DOAC) for 30 days prior to randomization.
    E.4Principal exclusion criteria
    1. Patients with moderate or severe mitral stenosis, mitral valve rheumatic disease, unresected atrial myxoma, or a mechanical heart valve (patients with bioprosthetic heart valves and/or valve repair can be included) and/or other conditions, such as pulmonary embolism, considered to be a formal indication for conventional anticoagulation;
     However patients with AF and valvular heart diseases such as mitral valve prolapse, mitral valve regurgitation, and aortic valve disease are allowed in the study as long as they are of non-rheumatic nature
    2. Patients with acute myocardial infarction, acute coronary syndrome, or percutaneous coronary intervention within the previous 30 days, or ischemic stroke within the previous 7 days; subjects with ischemic stroke more than 7 days prior to randomization can be included provided there is no evidence of haemorrhagic transformation
    3. Patients with any contraindication to anticoagulant agents;
    4. Patients with conditions associated with high risk of bleeding such as a past history of intracranial (spontaneous or traumatic), spontaneous intraocular, spinal, retroperitoneal or intra-articular bleeding; overt gastrointestinal bleeding or active ulcer within the previous year; recent severe trauma, major surgery, or deep organ biopsy within the previous 10 days; active infective endocarditis; uncontrolled hypertension (blood pressure [BP] above 170/100 mmHg); or hemorrhagic disorder including known or suspected hereditary or acquired bleeding or coagulation disorder;
    5. Patients anticipated to receive dual antiplatelet therapy (eg, aspirin plus thienopyridine such as clopidogrel, prasugrel, or ticagrelor) or aspirin alone at a dose > 100 mg daily during the study;
    6. Patients receiving or anticipated to continue fibrinolytics and patients anticipated to continue with prohibited concomitant medications, such as non-study anticoagulants, chronic oral or parenteral Non-Aspirin/Non-Steroidal Anti-Inflammatory Drugs (NSAID) for ≥ 4 days/week;
    7. Patients that are either receiving or are planned to receive the following oral P-gp inhibitors concomitantly: ciclosporine, dronedarone, erythromycin, or ketoconazole (topical formulations of ketoconazole or erythromycin are allowed);
    8. Patients with severe hepatic impairment or hepatic disease associated with coagulopathy (eg, acute hepatitis, chronic active hepatitis, cirrhosis);
    9. Patients with known liver disease and with a combination of alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) and total bilirubin (TBL) > 1.5 x ULN;
    10. Patients with hemoglobin < 10 g/dL or platelet count < 100,000 cells/mcL or white blood cell count < 3000 cells/mcL;
    11. Patients with planned invasive procedures (other than routine endoscopy) or surgeries in which bleeding is anticipated during the study period;
    12. Patients who received any investigational drug or device within 30 days prior to randomization, or plan to receive such investigational therapy during the study period;
    13. Women of childbearing potential not using proper contraceptive measures, and women who are pregnant or breast feeding;
    Note: Childbearing potential without proper contraceptive measures (ie, a method of contraception with a failure rate < 1 % during the course of the study (including the observational period). These methods of contraception according to the note for guidance on non-clinical safety studies for the conduct of human trials for pharmaceuticals (CPMP/ICH/286/95, modification) include consistent and correct use of hormone containing implants and injectables, combined oral contraceptives, hormone containing intrauterine devices, surgical sterilization, sexual abstinence, and vasectomy for the male partner);
    14. Patients with the following diagnoses or situations:
     Active cancer undergoing chemotherapy, radiation or major surgery within the next 3 months;
     Significant active concurrent medical illness or infection;
     Life expectancy < 12 months.
    15. Patients who are unlikely to comply with the protocol (eg, unable to swallow tablets whole uncooperative attitude, inability to return for subsequent visits, and/or otherwise considered by the Investigator to be unlikely to complete the study);
    16. Patients with a known drug or alcohol dependence within the past 12 months as judged by the Investigator;
    17. Patients with any condition that, in the opinion of the Investigator, would place the patient at increased risk of harm if he/she participated in the study.
    E.5 End points
    E.5.1Primary end point(s)
    PK/PD Endpoints:
    -edoxaban concentration (CAV, Cmin);
    -anti-FXa;
    -intrinsic FX, PT, aPTT.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Visit 2, 4, 6 and 9.
    E.5.2Secondary end point(s)
    Efficacy Endpoints:
    -composite of stroke/transient ischemic attack (TIA) and SEE (ischemic stroke, hemorrhagic stroke, TIA, and SEE).
    E.5.2.1Timepoint(s) of evaluation of this end point
    Throughout study duration
    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 Yes
    E.6.7Pharmacodynamic Yes
    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 No
    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 No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Edoxaban 60mg QD with active and placebo tablets maintaining the blind
    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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA139
    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
    Bulgaria
    Croatia
    Czech Republic
    Denmark
    Estonia
    Hungary
    Latvia
    Lithuania
    Poland
    Russian Federation
    Serbia
    Slovakia
    Spain
    Ukraine
    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
    LVLS
    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 months5
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months5
    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: 589
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 11
    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 state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 360
    F.4.2.2In the whole clinical trial 600
    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)
    Standard Care
    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 Decision2016-11-17
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-12-07
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-09-10
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA