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    Summary
    EudraCT Number:2015-001702-33
    Sponsor's Protocol Code Number:CV181-369
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2015-11-05
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2015-001702-33
    A.3Full title of the trial
    A 24-week International, Multicenter, Randomized, Open-Label, Active-Controlled, Parallel Group, Phase 3b Trial with a 28-week Extension to Evaluate the Efficacy and Safety of Saxagliptin Co-administered with Dapagliflozin Compared to Insulin Glargine in Subjects with Type 2 Diabetes who have Inadequate Glycemic Control on Metformin with or without Sulfonylurea Therapy
    Ensayo de fase IIIb internacional, multicéntrico, aleatorizado, abierto, controlado con producto activo, con grupos paralelos de 24 semanas de duración con una ampliación de 28 semanas para evaluar la eficacia y la seguridad de saxagliptina administrada conjuntamente con dapagliflozina en comparación con insulina glargina en pacientes con diabetes tipo 2 que presentan un control glucémico insuficiente con metformina con o sin sulfonilureas
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A comparison of treatment with Saxagliptin and Dapagliflozin against Insulin Glargine in Type 2 Diabetes patients whose current treatment of Metformin with or without Sulfonylurea Therapy is not adequate.
    Una comparación del tratamiento con saxagliptina y dapagliflozina contra la insulina glargina en pacientes diabéticos tipo 2, cuyo actual tratamiento de metformina con o sin terapia de sulfonilurea no es adecuada.
    A.4.1Sponsor's protocol code numberCV181-369
    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 SponsorAstraZeneca AB
    B.1.3.4CountrySweden
    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 supportAstraZeneca AB
    B.4.2CountrySweden
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationAstraZeneca
    B.5.2Functional name of contact pointInformation Center
    B.5.3 Address:
    B.5.3.1Street Address1800 Concord Pike, PO Box 15437
    B.5.3.2Town/ cityWilmington
    B.5.3.3Post code19850-5437
    B.5.3.4CountryUnited States
    B.5.4Telephone number34900 150 160
    B.5.6E-mailinformation.center@astrazeneca.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 Onglyza
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    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 nameSaxagliptin
    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 INNSAXAGLIPTIN
    D.3.9.1CAS number 361442-04-8
    D.3.9.2Current sponsor codeBMS-477118-11
    D.3.9.3Other descriptive nameSAXAGLIPTIN
    D.3.9.4EV Substance CodeSUB25220
    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 Yes
    D.2.1.1.1Trade name Forxiga
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca AB
    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 nameDapagliflozin
    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 INNDAPAGLIFLOZIN
    D.3.9.1CAS number 461432-26-8
    D.3.9.2Current sponsor codeBMS-512148
    D.3.9.3Other descriptive nameDAPAGLIFLOZIN
    D.3.9.4EV Substance CodeSUB31650
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number10
    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 Glargine Insulin
    D.2.1.1.2Name of the Marketing Authorisation holderSanofi-Aventis Deutschland GmbH
    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 nameGlargine Insulin
    D.3.4Pharmaceutical form 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 INNGlargine Insulin
    D.3.9.3Other descriptive nameINSULIN
    D.3.9.4EV Substance CodeSUB02689MIG
    D.3.10 Strength
    D.3.10.1Concentration unit U/ml unit(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    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
    Type 2 diabetes mellitus and inadequate glycemic control on a stable dose of metformin
    Diabetes tipo 2 que presentan un control glucémico insuficiente con metformina con o sin sulfonilureas
    E.1.1.1Medical condition in easily understood language
    Type 2 diabetes not being controlled by current medication
    Diabetes tipo 2 no controlados por medicación actual
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10049746
    E.1.2Term Insulin-requiring type II diabetes mellitus
    E.1.2System Organ Class 100000004861
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10063624
    E.1.2Term Type II diabetes mellitus inadequate control
    E.1.2System Organ Class 100000004861
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 18.1
    E.1.2Level LLT
    E.1.2Classification code 10045242
    E.1.2Term Type II diabetes mellitus
    E.1.2System Organ Class 100000004861
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To examine whether the mean change from baseline in HbA1c with co-administered saxagliptin 5 mg and dapagliflozin 10 mg plus metformin with or without SU is non-inferior to titrated insulin glargine plus metformin with or without SU after 24 weeks of open-label treatment.
    Examinar si la media del cambio en la HbA1c respecto a la línea basal logrado con la administración conjunta de 5 mg de saxagliptina y 10 mg de dapagliflozina más metformina con o sin sulfonilureas (SU) es no inferior a la de insulina glargina ajustada más metformina con o sin SU después de 24 semanas de tratamiento en abierto.
    E.2.2Secondary objectives of the trial
    ?To compare co-administered saxagliptin 5mg and dapagliflozin 10mg plus metformin with/without SU versus titrated insulin glargine plus metformin with/without SU after 24 weeks:
    - the mean change from baseline in total body weight
    - the proportion of confirmed hypoglycemia
    [defined as: a) plasma glucose ?70 mg/dL (3.9 mmol/L);
    or b) signs / symptoms of hypoglycemia with self-monitored blood glucose ?70 mg/dL (3.9 mmol/L)]
    - the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c < 7.0%, without any hypoglycemia.

    ?To examine whether with co-administered saxagliptin 5mg and dapagliflozin 10mg plus metformin with/without SU is non-inferior to titrated insulin glargine plus metformin with/without SU after 24 weeks:
    - the change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring
    - the proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c < 7.0%.
    Comparar:
    -la media del cambio en el peso corporal total respecto a la línea basal con la administración conjunta de 5 mg de saxagliptina y 10 mg de dapagliflozina más metformina con o sin SU en comparación con insulina glargina ajustada más metformina con o sin SU después de 24 semanas de tratamiento en abierto.
    -la proporción de hipoglucemia confirmada (definida como: a) glucosa plasmática ? 70 mg/dl [3,9 mmol/l]; o b) signos o síntomas de hipoglucemia con autocontrol de la glucemia? 70 mg/dl [3,9 mmol/l]) al administrar conjuntamente 5 mg de saxagliptina y 10 mg de dapagliflozina más metformina con o sin SU en comparación con insulina glargina ajustada más metformina con o sin SU después de 24 semanas de tratamiento en abierto. (ref a pag 4 del Protocolo v1.0)
    E.2.3Trial contains a sub-study Yes
    E.2.3.1Full title, date and version of each sub-study and their related objectives
    Continuous Glucose Monitoring (CGM) Sub-Study
    In the this study, a sub-population of approximately 250 subjects (approximately 125 subjects per treatment arm stratified by background SU use) who agree to participate (separate informed consent) will have a CGM sensor inserted subcutaneously to measure glucose levels in tissue fluid. The glucose sensor will be inserted and removed by trained personnel at the site. Subjects will wear the glucose sensor for (7) consecutive days at 4 different time periods during the study:
    ? At baseline, prior to receiving study medication, between Week -2 and Week-1
    ? Between Week 2 and Week 3 of treatment
    ? Between Week 11 and Week 12 of treatment
    ? Between Week 23 and Week 24 of treatment.
    Subjects in the sub-study will have (4) site visits added to the regularly scheduled visits (at Week -1, Week 3, Week 11 and Week 23). If CGM recording is insufficient at any of these timepoints, subjects may be required to wear the glucose sensor for an additional (7) day period to obtain sufficient data.
    Subjects in the CGM sub-study will be required to perform a 4-point SMBG profile on days of CGM monitoring when they are not performing the 6-point SMBG profile (see Section 5.3.1.2).
    This 4-point SMBG should be performed at the approximate times: before breakfast, before lunch, before dinner and before bedtime and the values recorded in the subject?s diary.

    Detailed procedures (including calibration, insertion/removal and upload of data) will be described in an operations manual and site staff will be trained on the use of the CGM. Subjects will be instructed on use of the device according to the manufacturer?s instructions.
    Subestudio de vigilancia continua de la glucosa (VCG)
    En este protocolo, a una subpoblación de aproximadamente 250 pacientes (aproximadamente 125 pacientes por grupo de tratamiento estratificados en función del uso de SU) que acepten participar (consentimiento informado independiente) se les introducirá subcutáneamente un sensor de VCG para medir las concentraciones de glucosa en el líquido intersticial. El sensor de glucosa será introducido y retirado por personal debidamente formado en el centro. Los pacientes llevarán el sensor de glucosa durante (7) días consecutivos en (4) períodos diferentes del estudio:
    ?En la línea basal, antes de recibir la medicación del estudio, entre las semanas -2 y -1.
    ?Entre las semanas 2 y 3 de tratamiento.
    ?Entre las semanas 11 y 12 de tratamiento.
    ?Entre las semanas 23 y 24 de tratamiento.
    Los pacientes del subestudio tendrán (4) visitas más al centro de las programadas normalmente (a las semanas -1, 3, 11 y 23) para supervisar la VCG. Si el registro de la VCG es insuficiente en alguno de estos momentos, se podrá pedir a los pacientes que lleven el sensor de glucosa durante otros (7) días para obtener suficientes datos.
    Durante el registro, ni los pacientes ni el investigador podrán disponer de los datos de la VCG.
    A los pacientes del subestudio de VCG se les pedirá que realicen un perfil de ACG de 4 puntos en los días de VCG en los que no estén realizando el perfil de ACG de 6 puntos (véase la sección 5.3.1.2). Este ACG de 4 puntos debe realizarse aproximadamente en los momentos siguientes: antes del desayuno, antes de la comida, antes de la cena y antes de acostarse. Los procedimientos detallados (incluida la calibración, la introducción y retirada y la carga de los datos) se describirán en un manual de operaciones, y el personal del centro recibirá formación sobre el uso de la VCG. Se darán instrucciones a los pacientes sobre el uso del dispositivo de acuerdo con las instrucciones del fabricante.
    E.3Principal inclusion criteria
    ? Males and females aged ? 18 years old at the time of screening visit.
    ? Subjects with T2DM with inadequate glycemic control, defined as a central laboratory HbA1c ? 8 % and ? 12 % obtained at the screening visit.
    ? Note: At Week -2 (Lead-In), a central laboratory fasting plasma glucose (FPG) qualification check will be performed. Subjects will only be randomized on Day 1 if their FPG is ? 270 mg/dL (15 mmol/L) at the Week -2 qualification check. A re-test will be permitted within (7) days if the Week -2 central lab FPG result was > 270mg/dL (15 mmol/L) but < 300 mg/dL (16.6 mmol/L). Subjects will be excluded if the central lab FPG value at Week -2 (Lead-In) is ? 300 mg/dL (16.6 mmol/L) or if the central lab FPG value at Week -2 (Lead-In) and the re-test FPG value are both > 270 mg/dL (15 mmol/L).
    ? Subjects must be taking a stable dose of metformin ? 1500 mg/day for at least 8 weeks prior to screening visit with or without a stable dose of SU of at least 50% maximal dose per local label for at least 8 weeks prior to screening visit. Subjects must not take any other antidiabetic therapy for more than 14 days (consecutive or not) during 12 weeks prior to screening.
    ? BMI ? 45.0 kg/m2 at the screening visit.
    ? Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) at screening and within 24 hours prior to the start of study drug.
    ?Hombres y mujeres que tengan ? 18 años en el momento de la visita de selección.
    ?Pacientes con DMT2 con un control glucémico insuficiente, definido como HbA1c según el laboratorio central ? 8 % y ?12 % obtenido en la visita de selección.
    ?Nota: en la semana -2 (preinclusión) se efectuará una comprobación de cualificación según la glucosa plasmática en ayunas (GPA) determinada en el laboratorio central. Solo se aleatorizará a los pacientes en el día 1 si su GPA es ? 270 mg/dl (15 mmol/l) en la comprobación de la cualificación de la semana -2. Se permitirá repetir las pruebas en un plazo de (7) días si el resultado de GPA del laboratorio central en la semana -2 es > 270 mg/dl (15 mmol/l), pero < 300 mg/dl (16,6 mmol/l). Se excluirá a los pacientes si el valor de GPA del laboratorio central en la semana -2 (preinclusión) ? 300 mg/dl (16,6 mmol/l) o si tanto el valor de GPA del laboratorio central en la semana -2 (preinclusión) como el valor del análisis repetido de GPA son > 270 mg/dl (15 mmol/l).
    ?Los pacientes deberán estar tomando una dosis estable de metformina ? 1.500 mg/día durante al menos 8 semanas antes de la visita de selección, con o sin una dosis estable de SU de al menos el 50 % de la dosis máxima según la ficha técnica local durante al menos 8 semanas antes de la visita de selección. Los pacientes no deben haber tomado ningún otro antidiabético durante más de 14 días (consecutivos o no) en las 12 semanas previas a la selección.
    ?IMC ? 45,0 kg/m2 en la visita de selección.
    ?Las mujeres en edad fértil (MEF) deben tener una prueba de embarazo negativa en suero u orina (sensibilidad mínima de 25 UI/l o unidades equivalentes de gonadotropina coriónica humana (human chorionic gonadotropin, HCG) en la selección y en las 24 horas anteriores al comienzo del tratamiento con el fármaco de estudio.
    E.4Principal exclusion criteria
    ? Clinical diagnosis of Type 1 Diabetes.
    ? History of unstable or rapidly progressing renal disease, hepatic insufficiency or current, acute or chronic pancreatitis.
    ? Any of the following cardiovascular/vascular diseases within 3 months of enrollment visit: MI, CABG, PTCA, valvular disease or repair, unstable angina or unstable CHF, TIA, Class III or IV heart failure, known left ventricular ejection fraction of < 40%, or significant cerebrovascular disease.
    ? Impairment of renal function (defined as creatinine clearance [CrCl] < 60 mL/min [estimated by Cockcroft-Gault] or serum creatinine [SCr] ? 1.5 mg/dL in males or ? 1.4 mg/dL in females).
    ? Hematuria (confirmed by microscopy at screening) with no explanation as judged by the investigator up to randomization. If bladder cancer is identified, subjects are not eligible to participate.
    ? Hematological or oncological diseases or conditions.
    ? Participation in a commercial weight loss program or history of bariatric surgery.
    ? Replacement or chronic systemic corticosteroid therapy.
    ? Administration of any other investigational drug or participation in any interventional clinical study within (30) days prior to screening for this study.
    ?Diagnóstico clínico de diabetes tipo 1.
    ?Antecedentes de nefropatía inestable o de progresión rápida, insuficiencia hepática o pancreatitis aguda o crónica en curso.
    ?Cualquiera de las enfermedades cardiovasculares o vasculares siguientes durante los 3 meses previos a la visita de inscripción: infarto de miocardio (IM), injerto de derivación aortocoronaria (IDAC), angioplastia coronaria transluminal percutánea (ACTP), valvulopatía o valvuloplastia, angina de pecho inestable o insuficiencia cardíaca congestiva (ICC) inestable, ataque isquémico transitorio (AIT), insuficiencia cardíaca de clases III o IV, fracción de eyección ventricular izquierda conocida < 40 % o enfermedad cerebrovascular significativa.
    ?Deterioro del funcionamiento renal (definido como aclaramiento de creatinina [creatinine clearance, CrCl] < 60 ml/min [estimado por la fórmula de Cockcroft-Gault] o creatinina sérica [Crs] ? 1,5 mg/dl en los hombres o ? 1,4 mg/dl en las mujeres).
    ?Hematuria (confirmada mediante microscopía en la selección) no filiada según el criterio del investigador hasta la aleatorización. Si se detecta cáncer de vejiga, los pacientes no serán aptos para participar.
    ?Enfermedades o afecciones hematológicas u oncológicas.
    ?Participación en programas comerciales de pérdida de peso o antecedentes de cirugía bariátrica.
    ?Tratamiento crónico o de reposición con corticoesteroides sistémicos.
    ?Administración de cualquier otro fármaco en investigación o participación en cualquier estudio clínico de intervención en los (30) días previos a la selección para este estudio.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in HbA1c at Week 24.
    Cambio en la HbA1c en la semana 24 respecto a la línea basal.
    E.5.1.1Timepoint(s) of evaluation of this end point
    At baseline, prior to receiving study medication, between Week -2 and Week -1, Week 24
    En la línea basal, antes de recibir la medicación del estudio, entre Semana -2 y Semana -1, Semana 24
    E.5.2Secondary end point(s)
    The secondary efficacy endpoints for the short-term treatment period include:
    1) Change from baseline in total body weight at Week 24
    2) Proportion of subjects with confirmed hypoglycemia [defined as: a) plasma glucose ? 70 mg/dL (3.9 mmol/L); or b) signs / symptoms of hypoglycemia with self-monitored blood glucose ? 70 mg/dL (3.9 mmol/L)] at Week 24
    3) Proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c < 7.0%, without any reported hypoglycemia (for the duration of the Short-term Period) at Week 24
    4) In a sub-study, change from baseline in the mean value of 24-hour glucose readings measured by Continuous Glucose Monitoring (CGM) at Week 2
    5) Proportion of subjects achieving a therapeutic glycemic response, defined as HbA1c < 7.0% at Week 24
    Los criterios de valoración secundarios de la eficacia para el período de tratamiento a corto plazo son:
    1) Cambio en el peso corporal total en la semana 24 respecto a la línea basal;
    2) Proporción de pacientes con hipoglucemia confirmada (definida como: a) glucosa plasmática  70 mg/dl [3,9 mmol/l]; o b) signos o síntomas de hipoglucemia con autocontrol de la glucemia  70 mg/dl [3,9 mmol/l]) en la semana 24;
    3) Proporción de pacientes que consiguen una respuesta glucémica terapéutica, definida como HbA1c < 7,0 %, sin ningún episodio de hipoglucemia descrito (durante el período de tratamiento a corto plazo) en la semana 24;
    4) En un subestudio, cambio producido desde la línea basal en el valor medio de las lecturas de glucosa de 24 horas obtenidas mediante vigilancia continua de la glucosa (VCG) en la semana 2;
    5) Proporción de pacientes que consiguen una respuesta glucémica terapéutica, definida como HbA1c < 7,0 %, en la semana 24.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) At baseline, prior to receiving study medication, between Week -2 and Week -1, Week 24
    2) Week 24
    3) Week 24
    4) At baseline, prior to receiving study medication, between Week -2 and Week -1, Week 24
    5) Week 24
    1) En la linea basal, antes de recibir la medicación del estudio, entre Semana -2 y -1 Semana, Semana 24 2) Semana 24 3) Semana 24 4) En la linea basal, antes de recibir la medicación del estudio, entre Semana -2 y -1 Semana, Semana 24 5) Semana 24
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open 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 concerned8
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA71
    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
    Czech Republic
    Denmark
    Germany
    Hungary
    Mexico
    Poland
    Romania
    Russian Federation
    South Africa
    Spain
    Sweden
    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
    LSLV
    Última visita último paciente
    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 months0
    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: 478
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 120
    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 253
    F.4.2.2In the whole clinical trial 598
    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)
    None
    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 Decision2016-01-22
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-12-28
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-11-10
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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