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    Summary
    EudraCT Number:2010-020002-15
    Sponsor's Protocol Code Number:A3921061
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2011-01-19
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2010-020002-15
    A.3Full title of the trial
    A PHASE 3, MULTI-SITE, OPEN-LABEL STUDY OF THE LONG TERM SAFETY AND TOLERABILITY OF 2 ORAL DOSES OF CP-690,550 IN SUBJECTS WITH MODERATE TO SEVERE CHRONIC PLAQUE PSORIASIS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Psoriasis
    A.3.2Name or abbreviated title of the trial where available
    A3921061 Long Term Open Label Extension Study/OPT Extend
    A.4.1Sponsor's protocol code numberA3921061
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT01163253
    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 SponsorPfizer Inc, 235 East 42nd Street, New York, NY 10017
    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 supportPfizer Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationPfizer Inc
    B.5.2Functional name of contact pointClinical Trials.gov Call Centre
    B.5.3 Address:
    B.5.3.1Street Address235 East 42nd Street
    B.5.3.2Town/ cityNew York
    B.5.3.3Post codeNY 10017, USA
    B.5.3.4CountryUnited States
    B.5.4Telephone number++18007181021
    B.5.5Fax number++13037391119
    B.5.6E-mailClinicalTrials.govCallCentre@pfizer.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 nameTofacitinib citrate (Phase III formulation)
    D.3.2Product code CP-690,550
    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 INNTOFACITINIB
    D.3.9.1CAS number 540737-29-9
    D.3.9.2Current sponsor codeCP-690,550
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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 nameTofacitinib citrate (Proposed commercial formulation – debossed)
    D.3.2Product code CP-690,550
    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 INNTOFACITINIB
    D.3.9.1CAS number 540737-29-9
    D.3.9.2Current sponsor codeCP-690,550
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    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
    Moderate To Severe Chronic Plaque Psoriasis
    E.1.1.1Medical condition in easily understood language
    Psoriasis
    E.1.1.2Therapeutic area Diseases [C] - Skin and Connective Tissue Diseases [C17]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.0
    E.1.2Level PT
    E.1.2Classification code 10037153
    E.1.2Term Psoriasis
    E.1.2System Organ Class 10040785 - Skin and subcutaneous tissue disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the long term safety and tolerability of treatment with tofacitinib (10 mg BID or variable dose 5 and 10 mg BID) in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
    E.2.2Secondary objectives of the trial
    - To evaluate the durability of efficacy of tofacitinib (10 mg BID or variable 5 and10 mg BID) in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.

    - To evaluate effects on patient reported outcome (PRO) measures during treatment with tofacitinib (10 mg BID or variable 5 and 10 mg BID) at various time points in adult subjects with moderate to severe chronic plaque psoriasis who are candidates for systemic therapy or phototherapy.
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Immungenicity Sub-study – A Study of Immune Response
    Following Administration of Pneumococcal and Tetanus Vaccines in Subjects from Study A3921061 with Moderate to Severe Chronic Plaque Psoriasis Receiving tofacitinib 10 mg BID. Protocol A3921061, February 2014, Appendix 10.

    This sub-study may be conducted in United States, Canada, Poland, Hungary and France. Additional countries may be added, if needed.

    Primary Objectives:
    •To characterize the effect of long-term exposure to 10 mg BID of tofacitinib on vaccine immunogenicity in subjects with moderate to severe chronic plaque psoriasis.

    Secondary Objectives:
    •To characterize the effect of long-term exposure to 10 mg BID of tofacitinib on humoral and cell mediated immunity in subjects with moderate to severe chronic plaque psoriasis, including analysis of lymphocyte subsets, vaccine specific antibody responses, and delayed-type hypersensitivity reactions.
    •To evaluate safety and tolerability of tofacitinib.

    A3921061 Viral Load Sub-study – A Study of Viral Load Levels of Epstein-Barr Virus (EBV) and Cytomegalovirus (CMV) and Lymphocyte Subsets in Subjects with Moderate to Severe Chronic Plaque Psoriasis Who Were Previously Enrolled in Study A3921047 and Continued Treatment in Study A3921061. Protocol A3921061, February 2014, Appendix 10.
    This sub-study will be conducted in United States and Canada.

    Primary Objectives:
    To evaluate changes from baseline in Study A3921047 in lymphocyte subsets and blood DNA levels of EBV and CMV using a quantitative PCR technique, in subjects with chronic plaque psoriasis who participated in the Pfizer Study A3921047 and are currently participating in Pfizer Study A3921061.
    E.3Principal inclusion criteria
    Inclusion Criteria that Apply to All subjects
    1.Evidence of a personally signed and dated informed consent document indicating that the subject (or a legal representative) has been informed of all pertinent aspects of the study
    2.Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures
    3.Be at least 18 years of age at time of consent
    4.Sexually active women of childbearing potential are required to use highly effective method of contraception during the study and for at least 28 days after treatment is discontinued.
    5.If receiving non-prohibited concomitant medications for any reason, must be on a stable regimen, which is defined as not starting a new drug or changing dosage within 7 days or 5 half-lives prior to first dose of study drug. Subject must be willing to stay on a stable regimen
    6.If received any of the following treatment regimens, for any reason, are eligible providing the following minimum washout criteria are observed:
    -Must be discontinued for at least 12 weeks prior to first dose of study drug
    a. Any investigational or experimental therapy or procedure for psoriasis, psoriatic arthritis or rheumatoid arthritis; Exception: Investigational biologics should be discussed with the Pfizer Medical Monitor to confirm period of discontinuation required. b. Ustekinumab (Stelara)
    -Must be discontinued for at least 8 weeks prior to first dose of study drug
    a. Adalimumab (Humira®) b. Infliximab (Remicade®) c. Alefacept (Amevive®)
    -Must be discontinued for at least 4 weeks prior to first dose of study drug;
    a. Etanercept (Enbrel®) not including potential treatment for subjects entering from qualifying protocol A3921080; Note: For subjects who participated in protocol A3921080, discontinuation from study drug treatment in protocol A3921080, for at least one week from Visit 5/Week 12 is required as washout criteria prior to entry into protocol A3921061.
    b. Systemic treatments other than biologics that could affect psoriasis, eg, oral or injectable (eg, intraarticular, intramuscular, or intravenous) corticosteroids, retinoids, methotrexate, cyclosporine, fumaric acid derivatives, sulfasalazine,hydroxycarbamide (hydroxyurea), azathioprine, intramuscular gold.
    c. Psoralens + UVA phototherapy (PUVA)
    -Must be discontinued for at least 2 weeks prior to first dose of study drug:
    a. Topical treatments that could affect psoriasis, eg, corticosteroids, tars,keratolytics, anthralin, vitamin D analogs, and retinoids; Exceptions – the following topical treatments are allowed: non-medicated emollients for use over the whole body; low or least potent (Class 6or7) topical corticosteroids for the palms, soles, face, and intertriginous areas and scalp only; tar and salicylic acid preparations for the scalp only, and shampoos free of corticosteroids for the scalp only.
    b. UVB (narrowband or broadband) phototherapy
    7.Must agree to avoid prolonged exposure to the sun and avoid use of tanning booths or other ultraviolet light sources during the study. Note: Per exclusion criterion, prior treatment with efalizumab (Raptiva®) is exclusionary.

    Inclusion Criteria that Apply only to Subjects who participated in Study A3921047
    1.Have previously completed study A3921047 or were withdrawn/discontinued from that study, with the exception that subjects that were withdrawn/discontinued due to a tofacitinib related serious adverse event are not eligible for this study.
    Inclusion Criteria that Apply only to (i) Subjects who Participated in Study A3921047 and (ii) Subjects who do not Enroll into This Study within a 2-week Window of the End of Study Visit of a Qualifying Phase 3 Study
    1.Subject must have evidence of plaque-type psoriasis (psoriasis vulgaris) and be considered by dermatologist investigator to be a candidate for systemic therapy or phototherapy of psoriasis at screening
    2.No evidence of active, latent or inadequately treated infection with Mycobacterium tuberculosis (TB) as defined by all of the following -A negative QuantiFERON-TB Gold (QFT-G) In-Tube test or if indeterminate upon retest, a Mantoux Purified Protein Derivative (PPD) skin or within the 3 months prior to Screening.
    -Chest radiographs, taken at or within the 3 months prior to a given Screening visit, without changes suggestive of active TB infection as determined by a qualified radiologist
    -No history of either untreated or inadequately treated latent or active TB infection
    For full criteria see section 4.1.3 of the protocol

    For sub-study inclusion criteria see Appendix 10, section 4.1.1 and Appendix 11, section 4.1.1 of the protocol.
    E.4Principal exclusion criteria
    Exclusion Criteria that Apply to All Subjects
    1.Currently have non-plaque forms of psoriasis, eg, erythrodermic, guttate, or pustular psoriasis, with the exception of nail psoriasis which is allowed
    2.Have evidence of skin conditions (eg, eczema) at the time of the screening or baseline visit that would interfere with evaluation of psoriasis.
    3.Have current drug-induced psoriasis, eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium channel blockers, antimalarial drugs or lithium
    4.If planned initiation of, or changes to, concomitant medication that could affect psoriasis (eg, beta blockers, calcium channel blockers, antimalarial drugs or lithium)are to occur within 2 weeks prior to randomization and/or during the study
    5.Cannot discontinue systemic therapies and/or topical therapies for the treatment of psoriasis and cannot discontinue phototherapy (UVB or PUVA)
    6.Are taking or require oral or injectable (eg, intramuscular, intravenous, intraarticular) corticosteroids for any condition.
    7.Women who are pregnant or lactating, or planning pregnancy while enrolled in the study. Women of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for at least 28 days after last dose of investigational product
    8.Have current or recent history of severe, progressive, or uncontrolled renal, hepatic,hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiovascular, or neurological disease.
    9.Have a history of any lymphoproliferative disorder (such as Epstein Barr Virus [EBV]-related lymphoproliferative disorder, as reported in some subjects on other immunosuppressive drugs), history of lymphoma, leukemia, or signs and symptoms suggestive of current lymphatic disease
    10.Have a history (single episode) of disseminated herpes zoster or disseminated herpes simplex, or a recurrent (more than one episode of) localized, dermatomal herpes zoster
    11. Have a history of infection requiring hospitalization, parenteral antimicrobial therapy, or as otherwise judged clinically significant by the investigator within 6 months prior to first dose of study drug.
    12.Have been either vaccinated with live or attenuated vaccine within the 6 weeks prior to the first dose of study drug, or expects to be vaccinated with these vaccines during treatment, or within the 6 weeks following discontinuation of study drug
    13.Any prior treatment with non B cell-specific lymphocyte depleting agents/therapies.Subjects who have received rituximab or other selective B lymphocyte depleting agents (including experimental agents) are eligible if they have not received such therapy for at least 1 year prior to first dose of study drug and have normal CD 19/20+ counts by FACS analysis
    14.Have previously been treated with efalizumab (Raptiva®)
    15.Have any condition possibly affecting oral drug absorption, eg, gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgerysuch as gastric bypass. Procedures such as gastric banding, that simply divide the stomach into separate chambers, are NOT exclusionary
    16.Have a history of alcohol or substance abuse, unless in full remission for greater than 6 months prior to first dose of study drug
    17.Have a known immunodeficiency disorder or first-degree relative with a hereditary immunodeficiency
    18.Have any malignancies or have a history of malignancies with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
    19.Have undergone significant trauma or major surgery within 1 month prior to Screening
    20. Require treatment with prohibited concomitant medication(s) including prohibited dietary supplements or have received a prohibited concomitant medication/dietary supplement within 7 days or 5 half-lives prior to the first dose of study drug. Note: amiodarone requires discontinuation at least 290 days (5 half-lives) prior to the first dose of study drug
    21. Known to be infected with human immunodeficiency virus (HIV), hepatitis B or hepatitis C viruses. For additional Japan specific requirement approved in Japan country specific protocol amendment 8, see Appendix 6.

    For Exclusion Criteria numbers 22 - 26, please see section 4.2.1 of the protocol.

    For Exclusion Criteria that Apply only to (i) Subjects who Participated in Study A3921047 and (ii) Subjects who do not Enroll into This Study within a 2-week Window of the End of Study Visit of a Qualifying Phase 3 Study or study A3921147 see section 4.2.2 of the protocol

    For Exclusion Criteria that Apply only to Subjects who Enroll from a Qualifying Phase 3 Study within a 2-week Window of the End of Study Visit or study A3921147 see section 4.2.3 of the protocol

    For Exclusion Criteria for the A3921061 Immungenicity Sub-study see Appendix 10, section 4.1.2 of the protocol.
    E.5 End points
    E.5.1Primary end point(s)
    This protocol uses independent endpoint adjudication committees to determine whether certain investigator-reported events meet the definition of disease-related efficacy endpoints, using pre-defined endpoint criteria.
    - Incidence and severity of adverse events during treatment.
    - Incidence of clinical laboratory abnormalities and change from baseline (in this and/or prior study) in clinical laboratory values during treatment.
    - Incidence of investigator-reported clinically significant changes in physical examination from baseline (in this and/or prior study) during treatment.
    - Incidence of vital sign (blood pressure and heart rate) abnormalities and change from baseline (in this and/or prior study) in vital sign measures during treatment.
    - Incidence of electrocardiogram (ECG) abnormalities and change from baseline (in this and/or prior study) in ECG measurements during treatment using data obtained until the implementation of Protocol Amendment 17.
    - Summary of adjudicated cardiovascular endpoints.
    - Summary of malignancies confirmed by central laboratory pathologist over-read of biopsies.

    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline/Day 1, Months 3, 6, 9, and 12 and thereafter every 3 months. Open-Label ~5 years

    Timepoint of evaluation of this end point for the A3921061 Immungenicity Sub-study:
    1. Fold rise of serotype-specific opsonophagocytic assay (OPA) titers for each of the 13 serotypes from vaccine sub-study baseline/Visit 1 (Day 1, prevaccination) to vaccine sub-study Visit 3 (Day 31).
    2. Proportion of subjects achieving a satisfactory humoral response to the tetanus vaccine as defined by ≥2-fold increase from baseline/Visit 1 (Day 1, prevaccination) in antitetanus toxoid IgG titer for patients with prevaccination tetanus toxoid antibody titers ≥0.1 IU/ml, or a titer ≥0.2 IU/ml for subjects with prevaccination titers <0.1 IU/ml measured at vaccine sub-study Visit 3 (Day 31).
    E.5.2Secondary end point(s)
    Physician’s Global Assessment (PGA) response ie, the proportion of subjects achieving a PGA of “clear” or “almost clear” at various time points.
    - Psoriasis Area and Severity Index 75 (PASI75) response ie, the proportion of subjects achieving at least a 75% reduction in PASI relative to Baseline/Day 1 (in this and/or prior study) at various time points. The actual and change from Baseline/Day 1 (in this and/or prior study) in PASI and PASI component scores at various time points. The proportion of subjects achieving at least a 50% and 90% reduction in PASI relative to Baseline/Day 1 (in this and/or prior study) (ie, PASI50 and PASI90, respectively) at various time points. Proportion of subjects with a PASI score ≥125% of the Baseline/Day 1 PASI score (in this and/or prior study) at any time point. The actual and change from Baseline/Day 1 (in this and/or prior study) in the Itch Severity Item (ISI) score at various time points. The actual and change from Baseline/Day 1 (in this and/or prior study) on the Dermatology Life Quality Index (DLQI) score at various time points. Other patient reported outcome (PRO) measures to be assessed at various time points, including: Short Form-36 Health Survey (Version 2, Acute) (SF-36);
    -Patient Global Assessment (PtGA);
    -Euro-Qol 5 Dimensions (EQ-5D);
    - Psoriasis Healthcare Resource Utilization Questionnaire (Ps-HCRU).
    After implementation of Protocol Amendment 17, certain PROs (eg, SF-36, EQ-5D, Ps-HCRU) will not be assessed.

    Secondary End Point for the A3921061 Immungenicity Sub-study:
    1.Antibody response to each of the 13 pneumococcal antigens as measured by serotype-specific OPA titers at vaccine sub-study baseline/Visit 1 (Day 1, prevaccination) and 4 weeks post-vaccination on vaccine sub-study Visit 3 (Day 31).
    2. Proportion of subjects achieving serotype-specific OPA titers ≥ lower limit of quantitation (LLOQ) of the assay.
    3. IgG titers to each of the 13 serotype-specific pneumococcal antigens as measured by ELISA at vaccine sub-study baseline/Visit 1 (Day 1, prevaccination) and 4 weeks post-vaccination on vaccine sub-study Visit 3 (Day 31).
    4. Fold rise of IgG titers to each of the 13 serotype-specific pneumococcal antigens as measured by ELISA from vaccine sub-study baseline/Visit 1 (Day 1, prevaccination) and 4 weeks post-vaccination on vaccine sub-study Visit 3 (Day 31).
    5. IgG titers to tetanus toxoid at vaccine sub-study baseline/Visit 1 (Day 1, prevaccination) and 4 weeks post-vaccination on vaccine sub-study Visit 3 (Day 31).
    6. Proportion of subjects who respond to tetanus toxoid as defined by ≥4-fold increase in antibody titers from baseline/Visit 1 (Day 1, prevaccination) measured at vaccine sub-study Visit 3 (Day 31).
    7. Fold increase in anti-tetanus toxoid antibodies above baseline/Visit 1 (Day 1, prevaccination) values at vaccine sub-study Visit 3 (Day 31).
    8. Delayed-type hypersensitivity reaction
    a. Proportion of subjects with a positive DTH reaction following intracutaneous challenge with tetanus toxoid with a positive response defined as an induration ≥5 mm as measured 48 hrs after tetanus toxoid challenge on vaccine sub-study baseline/Visit 1 (Day 1) and Visit 3 (Day 31).
    9. Safety parameters, including clinical safety laboratory testing (hematology, chemistry, urinalysis), physical exam and vital signs (blood pressure and temperature), and assessment of adverse events.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Assessment of secondary endpoints are defined within the protocol
    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 Yes
    E.6.13.1Other scope of the trial description
    Tolerability - effects on patient reported outcome
    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 No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    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 No
    E.8.2.4Number of treatment arms in the trial1
    E.8.3 The trial involves single site in the Member State concerned Information not present in EudraCT
    E.8.4 The trial involves multiple sites in the Member State concerned Information not present in EudraCT
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA222
    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
    Argentina
    Australia
    Austria
    Belgium
    Bosnia and Herzegovina
    Brazil
    Bulgaria
    Canada
    Chile
    Colombia
    Croatia
    Czech Republic
    Denmark
    Finland
    France
    Germany
    Greece
    Hong Kong
    Hungary
    Israel
    Italy
    Korea, Republic of
    Mexico
    Netherlands
    Poland
    Portugal
    Serbia
    Singapore
    Slovakia
    Spain
    Sweden
    Switzerland
    Taiwan
    Turkey
    Ukraine
    United Arab Emirates
    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
    As per protocol section 13.1.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years5
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days26
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1Number of subjects for this age range: 0
    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: 2880
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 320
    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 Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    A Legal representative can give consent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 1648
    F.4.2.2In the whole clinical trial 3200
    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)
    After the subject has ended his/her participation in the trial, normal treatment is expected to resume based on their health care provider’s standard of 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 Decision2011-01-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-01-27
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-06-22
    The status of studies in GB is no longer updated from 1.1.2021
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