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    Summary
    EudraCT Number:2012-000128-16
    Sponsor's Protocol Code Number:2011-003
    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:2012-05-01
    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 number2012-000128-16
    A.3Full title of the trial
    A Randomized, Open-label, Phase 3 Study of Carfilzomib Plus Dexamethasone vs Bortezomib Plus Dexamethasone in Patients With Relapsed Multiple Myeloma
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical Study to Test the Effectiveness of Carfilzomib Plus Dexamethasone Versus Bortezomib Plus Dexamethasone in Patients with Multiple Myeloma (Bone Marrow Cancer)
    A.4.1Sponsor's protocol code number2011-003
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01568866
    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 SponsorOnyx Therapeutics, 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 supportOnyx Therapeutics, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAmgen (EUROPE) GmbH
    B.5.2Functional name of contact pointIHQ medical Info-Clinical Trials
    B.5.3 Address:
    B.5.3.1Street AddressDammstrasse 23, P.O. Box 1557
    B.5.3.2Town/ cityZug
    B.5.3.3Post codeCH 6300
    B.5.3.4CountrySwitzerland
    B.5.6E-mailMedinfoInternational@amgen.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 Krypolis
    D.2.1.1.2Name of the Marketing Authorisation holderAmgen Europe B.V
    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 Yes
    D.2.5.1Orphan drug designation numberEU/3/08/548
    D.3 Description of the IMP
    D.3.1Product nameCarfilzomib
    D.3.2Product code PR-171
    D.3.4Pharmaceutical form Powder for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCarfilzomib
    D.3.9.1CAS number 868540-17-4
    D.3.9.2Current sponsor codePR-171
    D.3.9.3Other descriptive nameFP-101; 506160
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2
    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 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 Yes
    D.2.1.1.1Trade name Velcade
    D.2.1.1.2Name of the Marketing Authorisation holderJANSSEN-CILAG INTERNATIONAL NV
    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.3.1Product nameVelcade
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBORTEZOMIB
    D.3.9.1CAS number 179324-69-7
    D.3.9.4EV Substance CodeSUB20020
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    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 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 Yes
    D.2.1.1.1Trade name Velcade
    D.2.1.1.2Name of the Marketing Authorisation holderJANSSEN-CILAG INTERNATIONAL NV
    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.3.1Product nameVelcade
    D.3.4Pharmaceutical form Powder for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNBORTEZOMIB
    D.3.9.1CAS number 179324-69-7
    D.3.9.4EV Substance CodeSUB20020
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number2.5
    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: 4
    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 Yes
    D.2.1.1.1Trade name Dexamethason-ratiopharm® 4 mg Tabletten
    D.2.1.1.2Name of the Marketing Authorisation holderratiopharm GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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 nameDexamethasone
    D.3.4Pharmaceutical form 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 INNDEXAMETHASONE ACEFURATE
    D.3.9.1CAS number 83880-70-0
    D.3.9.4EV Substance CodeSUB07018MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number4
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Multiple myeloma
    E.1.1.1Medical condition in easily understood language
    Bone marrow cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.0
    E.1.2Level LLT
    E.1.2Classification code 10028228
    E.1.2Term Multiple myeloma
    E.1.2System Organ Class 100000004864
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare progression-free survival (PFS) in patients with multiple myeloma relapsed after 1 to 3 prior therapies treated with either carfilzomib plus dexamethasone (Cd) or bortezomib (Velcade®) plus dexamethasone (Vd).
    E.2.2Secondary objectives of the trial
    To compare the following between the treatment groups:
    - Overall Survival (OS)
    - Overall Response Rate (ORR) [defined as the proportion of best
    overall response of stringent Complete Response (sCR), Complete
    Response (CR), Very Good Partial Response (VGPR), and Partial
    Response (PR)]
    - Duration of Response (DOR)
    - Neuropathy Events (defined from Grade 2 or higher peripheral
    neuropathy)
    - Safety and Tolerability - Assess changes from baseline in LVEF, RV function, and pulmonary artery pressure in a subset of patients from both treatment groups
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Pharmacokinetic sub-study:
    Blood samples will be collected from approximately 100 patients in the Cd arm for measurement of plasma carfilzomib concentrations and subsequent estimation of a number of pharmacokinetic parameters.

    Pharmacodynamics and Biomarkers sub-study:
    Pharmacodynamics in the form of proteasome inhibition will be measured in whole blood and isolated peripheral blood mononuclear cells collected from at least 15 patients per treatment arm. Analysis of biomarkers predictive of response to proteasome inhibitors will also be performed on these samples, as will genomic and proteomic analyses in an attempt to determine biomarkers that predict for response metrics and safety signals.
    ECHO sub-study:
    A transthoracic ECHO to assess LVEF, RV function, right ventricular size, right ventricular wall thickness, and pulmonary artery pressure will be obtained on all patients at baseline prior to the start of therapy. A subset of patients from both arms (a minimum of 100 patients and a maximum of 300 patients total; 50 to 150 patients per treatment arm) will be assessed for LVEF, RV function, right ventricular size, right ventricular wall thickness, and pulmonary artery pressure every 12 weeks and at end of treatment. A clinical adjudication committee composed of 2 to 3 cardiologists who will review all echocardiographic data in conjunction with available clinical (e.g., signs or symptoms of
    CHF, cardiac ischemia, conduction abnormalities) and diagnostic
    correlates (e.g., results of stress test, ECG, cardiac angiogram, cardiac catheterization) from substudy patients who exhibit incidental changes in LVEF, RV function or pulmonary artery pressure in order to assess their clinical relevance.
    For patients who present acutely with signs or symptoms of CHF,
    cardiac ischemia or conduction abnormalities an ECG and ECHO
    should be performed. As part of the evaluation, additional diagnostic tests such as a stress test, chest x-ray and CT angiogram could be performed. For patients who present with a clinically significant pulmonary adverse event such as dyspnea or hypoxia, the time course of onset and resolution of the event must be recorded and oximetry and/or blood gases measurements as well as response to oxygen supplementation. Consultation with a pulmonary specialist should occur when clinically appropriate. Any patient with emergent cardiac and/or pulmonary toxicities will have the cardiopulmonary adverse event eCRF completed.
    Minimal Residual Disease (MRD) testing:
    A bone marrow aspirate will be collected in patients who consent to the optional MRD assessment by flow cytometry, at the time of CR, sCR, or VGPR, and in consenting patients with previously established CR or sCR, and will be analyzed for the presence of MRD. The MRD analysis will only be performed in countries that meet local tissue sample transportation requirements.
    E.3Principal inclusion criteria
    1.Multiple myeloma with relapsing or progressing disease at study entry.
    2.Patients must have evaluable multiple myeloma with, at least one of the following (assessed within 21 days prior to randomization):
    •Serum M-protein ≥ 0.5 g/dL, or
    •Urine M-protein ≥ 200 mg/24 hour, or
    •In patients without detectable serum or urine M-protein, serum free light chain (FLC) > 100 mg/L (involved light chain) and an abnormal serum kappa/lambda ratio, or
    •For IgA patients whose disease can only be reliably measured by serum quantitative immunoglobulin (qIgA) ≥ 750 mg/dL (0.75 g/dL).
    3.Patients must have documented at least PR to at least 1 line of prior therapy. PR documentation can be based on Investigator assessment.
    4. Received at least 1, but no more than 3 prior treatment regimens or lines of therapy for multiple myeloma. (Induction therapy followed by stem cell transplant and consolidation/ maintenance therapy will be considered as one line of therapy).
    5. Prior therapy with Velcade is allowed as long as the patient had at least a PR to prior Velcade therapy, was not removed from Velcade therapy due to toxicity, and will have at least a 6 month Velcade treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month Velcade treatment-free interval).
    6. Prior therapy with carfilzomib is allowed as long as the patient had at least a PR to prior carfilzomib therapy, was not removed from carfilzomib therapy due to toxicity, and had at least a 6-month carfilzomib treatment-free interval from last dose received until first study treatment. (Patients may receive maintenance therapy with drugs that are not in the proteasome inhibitor class during this 6 month carfilzomib treatment-free interval). The exception to this are patients randomized or previously randomized in any other Onyx-Sponsored Ph 3
    trial
    7.Males and females ≥ 18 years of age.
    8. ECOG Performance Status of 0 to 2.
    9. Adequate hepatic function within 21 days prior to randomization, with bilirubin < 1.5 times the ULN, and AST and ALT < 3 times the ULN.
    10. LVEF ≥ 40%.
    11. ANC ≥ 1000/mm3 within 21 days prior to randomization. Screening ANC should be independent of growth factor support for ≥ 1 week.
    12. Hemoglobin ≥ 8.0 g/dL within 21 days prior to randomization. Use of erythropoietic stimulating factors and RBC transfusions per institutional guidelines is allowed, however most recent RBC transfusion may not have been done within 7 days prior to obtaining screening hemoglobin.
    13. Platelet count ≥ 50,000/mm3 (≥ 30,000/mm3 if myeloma
    involvement in the bone marrow is > 50%) within 21 days prior to randomization. Patients should not have received platelet transfusions for at least 1 week prior to obtaining the screening
    platelet count.
    14. Calculated or measured CrCl of ≥ 15 mL/min within 21 days prior to randomization. Calculation should be based on standard formula such as the Cockcroft and Gault: [(140 – Age) x Mass (kg) / (72 x Creatinine mg/dL)]; multiply result by 0.85 if female.
    15. Written informed consent in accordance with federal, local, and institutional guidelines.
    16. Female patients of childbearing potential (FCBP) must have a
    negative serum pregnancy test within 21 days prior to randomization and agree to use an effective method of contraception during and for 3 months following last dose of drug (more frequent pregnancy tests may be conducted if
    required per local regulations). FCBP is defined as a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months).
    17. Male patients must agree to use an effective barrier method of contraception during study and for 3 months following the last dose if sexually active with a FCBP.
    E.4Principal exclusion criteria
    1. Multiple myeloma of IgM subtype.
    2. Glucocorticoid therapy (prednisone > 30 mg/day or equivalent) within 14 days prior to randomization.
    3. POEMS syndrome.
    4. Plasma cell leukemia or circulating plasma cells ≥ 2 × 109/L.
    5. Waldenstrom’s Macroglobulinemia.
    6. Patients with known amyloidosis.
    7. Chemotherapy with approved or investigational anticancer therapeutics within 21 days prior to randomization.
    8. Patients randomized or previously randomized in any other Onyx-sponsored Phase 3 trial.
    9. Focal radiation therapy within 7 days prior to randomization. Radiation therapy to an extended field involving a significant volume of bone marrow within 21 days prior to randomization (i.e., prior radiation must have been to less than 30% of the bone marrow).
    10. Immunotherapy within 21 days prior to randomization.
    11. Major surgery (except kyphoplasty) within 28 days prior to randomization.
    12. Active congestive heart failure (NYHA Class III to IV; refer to Appendix H), symptomatic ischemia, or conduction abnormalities uncontrolled by conventional intervention. Myocardial infarction within four months prior to randomization.
    13. Acute active infection requiring systemic antibiotics, antiviral (except antiviral therapy directed at hepatitis B) or antifungal agents within 14 days prior to randomization.
    14. Known HIV seropositive, hepatitis C infection, and/or hepatitis B (except for patients with hepatitis B SAg or core antibody receiving and responding to antiviral therapy directed at hepatitis B: these patients are allowed).
    15. Patients with known cirrhosis.
    16. Second malignancy within the past 3 years except:
    - adequately treated basal cell or squamous cell skin cancer
    - carcinoma in situ of the cervix
    - prostate cancer Gleason score ≤ 6 with stable prostatespecific antigen (PSA) over 12 months
    - breast carcinoma in situ with full surgical resection
    - treated medullary or papillary thyroid cancer
    17. Patients with myelodysplastic syndrome.
    18. Significant neuropathy (Grades 3 to 4, or Grade 2 with pain) within 14 days prior to randomization.
    19. Female patients who are pregnant or lactating.
    20. Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib)
    21. Patients with hypersensitivity to carfilzomib, Velcade, boron, or mannitol.
    22. Patients with contraindication to dexamethasone.
    23. Contraindication to any of the required concomitant drugs or supportive treatments,including hypersensitivity to antiviral drugs, or intolerance to hydration due to preexisting pulmonary or cardiac impairment.
    24. Ongoing graft-vs-host disease.
    25. Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to randomization.
    26. Any other clinically significant medical disease or psychiatric condition that, in the Investigator’s opinion, may interfere with protocol adherence or a patient’s ability to give informed consent.
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is PFS by Independent Review Committee (IRC)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Study is expected to have required number of PFS events approximately 8 months after enrollment is complete
    E.5.2Secondary end point(s)
    The secondary endpoints are:
    •Overall survival
    •Overall Response Rate (defined as the proportion of best overall response of sCR, CR, VGPR, and PR)
    •Duration of Response
    •Neuropathy Events (defined from Grade 2 or higher peripheral neuropathy)
    •Safety and Tolerability:
    Change from baseline in LVEF, RV function, and pulmonary artery pressure in a subset of patients from both treatment
    groups
    E.5.2.1Timepoint(s) of evaluation of this end point
    Secondary end points are to be evaluated at the time of the final OS analysis when the required number of events have been reached, estimated at approximately 78 months after the enrollment start.

    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 Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic Yes
    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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 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 concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA84
    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
    Australia
    Austria
    Belgium
    Brazil
    Bulgaria
    Canada
    Czech Republic
    France
    Germany
    Greece
    Hungary
    Israel
    Italy
    Korea, Republic of
    New Zealand
    Poland
    Romania
    Russian Federation
    Singapore
    Slovakia
    Spain
    Taiwan
    Ukraine
    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
    End of the study defined as when the final OS analysis takes place
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years6
    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 years6
    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: 592
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 296
    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 state40
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 340
    F.4.2.2In the whole clinical trial 888
    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)
    As per protocol
    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 Decision2012-06-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-08-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-02-05
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