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    Summary
    EudraCT Number:2012-003948-67
    Sponsor's Protocol Code Number:331-12-282
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2013-09-05
    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 number2012-003948-67
    A.3Full title of the trial
    A Phase 3, Multicenter, Randomized, Double-blind, Placebo- and Active Comparatorcontrolled
    Trial of Flexible-dose Brexpiprazole (OPC-34712) as Adjunctive Therapy in the Treatment of Adults With Major Depressive Disorder, the Delphinus Trial
    Estudio de fase 3, multicéntrico, aleatorizado, doble ciego, controlado con placebo y con comparador activo de la administración de brexpiprazol (OPC-34712) en dosis flexible como tratamiento adyuvante de adultos con trastorno depresivo mayor: Estudio Delphinus
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    not available
    A.3.2Name or abbreviated title of the trial where available
    Delphinus
    Delphinus
    A.4.1Sponsor's protocol code number331-12-282
    A.5.4Other Identifiers
    Name:IND No.Number:103, 958
    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 SponsorOtsuka Pharmaceutical Development & Commercialization,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 supportOtsuka Pharmaceutical Development & Commercialization,Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationINC Research
    B.5.2Functional name of contact pointRegulatory Project Manager
    B.5.3 Address:
    B.5.3.1Street Addressc/Rosa de Lima, 1 bis
    B.5.3.2Town/ cityLas Matas- Madrid
    B.5.3.3Post code28290
    B.5.3.4CountrySpain
    B.5.4Telephone number+34916307400
    B.5.5Fax number+34916307474
    B.5.6E-mailricardo.sanz-gadea@incresearch.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 nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    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 INNBrexpiprazole
    D.3.9.2Current sponsor codeOPC-34712
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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 Seroquel XR
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca Pharmaceuticals LP
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameSeroquel
    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 INNQUETIAPINE FUMARATE
    D.3.9.1CAS number 111974-69-7
    D.3.9.3Other descriptive nameQUETIAPINE FUMARATE
    D.3.9.4EV Substance CodeSUB15074MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number50
    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 nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    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 INNBrexpiprazole
    D.3.9.2Current sponsor codeOPC-34712
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    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 Seroquel XR
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca Pharmaceuticals LP
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameSeroquel
    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 INNQUETIAPINE FUMARATE
    D.3.9.1CAS number 111974-69-7
    D.3.9.3Other descriptive nameQUETIAPINE FUMARATE
    D.3.9.4EV Substance CodeSUB15074MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number150
    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: 5
    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 Seroquel XR
    D.2.1.1.2Name of the Marketing Authorisation holderAstraZeneca Pharmaceuticals LP
    D.2.1.2Country which granted the Marketing AuthorisationUnited States
    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 nameSeroquel
    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 INNQUETIAPINE FUMARATE
    D.3.9.1CAS number 111974-69-7
    D.3.9.3Other descriptive nameQUETIAPINE FUMARATE
    D.3.9.4EV Substance CodeSUB15074MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number300
    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: 6
    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 nameBrexpiprazole (OPC-34712)
    D.3.2Product code Brexpiprazole (OPC-34712)
    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 INNBrexpiprazole
    D.3.9.2Current sponsor codeOPC-34712
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    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.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule, hard
    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
    Major Depressive Disorder (MDD)
    Trastorno Depresivo Mayor (TDM)
    E.1.1.1Medical condition in easily understood language
    Major Depressive Disorder (MDD)
    Trastorno Depresivo Mayor (TDM)
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 14.1
    E.1.2Level LLT
    E.1.2Classification code 10025454
    E.1.2Term Major depressive disorder, recurrent episode
    E.1.2System Organ Class 100000004873
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare the efficacy of brexpiprazole (flexible
    dose) with placebo as adjunctive therapy to an assigned openlabel
    antidepressant therapy (ADT) in the proposed subject
    population with MDD.
    Comparar la eficacia de brexpiprazol (en dosis flexible) con la del placebo como adyuvante del tratamiento antidepresivo (TAD) no enmascarado asignado en la población propuesta de pacientes con TDM.
    E.2.2Secondary objectives of the trial
    Secondary: To evaluate the safety and tolerability of
    brexpiprazole (flexible dose) as adjunctive therapy to ADT in
    the proposed subject population with MDD.
    Evaluar la seguridad y tolerabilidad de brexpiprazol (en dosis flexible) como adyuvante del TAD en la población propuesta de pacientes con TDM.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subjects who are able to provide written informed consent and/or consent obtained from a legally acceptable representative (as required by IRB/IEC) prior to the initiation of any protocol-required procedures.
    2. Ability, in the opinion of the principal investigator, to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet/capsule ingestion, and discontinuation of prohibited concomitant medication; to read and understand the written word in order to complete subject-reported outcomes measures; and to be reliably rated on assessment scales.
    3. Male and female outpatients 18 to 65 years of age, inclusive, at the time of informed consent.
    4. Subjects with both a diagnosis of MDD, and in a current major depressive episode, as defined by DSM-IV-TR criteria and confirmed by both the M.I.N.I. and an adequate clinical psychiatric
    evaluation. The current major depressive episode must be >= 8 weeks in duration. In addition, subjects must have reported a history for the current major depressive episode of an inadequate
    response to at least one and no more than 3 adequate antidepressant treatments. An inadequate response is defined as < 50% reduction in depressive symptom severity, as assessed by the ATRQ. Adequate treatment is defined as an antidepressant treatment for at least 6 weeks in duration at a
    minimum dose (or higher) as specified in the ATRQ. If the subject showed >= 50% improvement on any antidepressant treatment in the current episode, then the subject must have had an inadequate response to a subsequent adequate antidepressant treatment (as defined above by the ATRQ) of another antidepressant drug prior to entry into the trial. For the most recent antidepressant treatment, the subject must not report
    >= 50% improvement (as defined above by the ATRQ).
    5. Subjects with MADRS Total Score >= 26 at the Screening and Baseline visits.
    6. Subjects willing to discontinue all prohibited psychotropic medications to meet protocol-required washouts prior to and during the trial period.
    1. Pacientes que puedan proporcionar el consentimiento informado por escrito u obtención del consentimiento de un representante legalmente aceptable (según lo requiera el IRB/CEIC), antes de comenzar ningún procedimiento requerido por el protocolo.
    2. Capacidad, según la opinión del investigador principal, de comprender la naturaleza del estudio y cumplir los requisitos del protocolo, inclusive los regímenes posológicos prescritos, la toma de comprimidos o cápsulas y la interrupción de los medicamentos simultáneos prohibidos; también de leer y comprender textos escritos para poder rellenar las mediciones de resultados comunicados por el paciente y recibir una puntuación fiable en las escalas de evaluación.
    3. Pacientes ambulatorios de ambos sexos de 18 a 65 años de edad, ambas inclusive, en el momento del consentimiento informado.
    4. Pacientes con diagnóstico de TDM y un episodio depresivo mayor actual, definido según los criterios del DSM-IV-TR y confirmado mediante la MINI y mediante una evaluación psiquiátrica clínica adecuada El episodio actual depresivo mayor debe haber durado al menos 8 semanas. Además, los pacientes deben haber aportado información en el episodio depresivo mayor actual de una respuesta inadecuada de al menos1 y no más de 3 tratamientos antidepresivos apropiados. Se define como respuesta inadecuada la reducción inferior al 50 % de la intensidad de los síntomas de depresión, evaluada mediante el ATRQ. Se define como tratamiento adecuado el tratamiento antidepresivo de una duración de al menos 6 semanas con una dosis mínima (o mayor) tal como se especifica en el ATRQ. Si el paciente demostró una mejoría de al menos el 50 % con cualquier tratamiento antidepresivo en el episodio actual, debe presentar una respuesta inadecuada a otro tratamiento antidepresivo apropiado recibido con posterioridad (tal como se define antes en el ATRQ) antes de su incorporación al estudio. En relación con este tratamiento antidepresivo más reciente, el paciente no debe referir una mejoría del 50 % o mayor (tal como se define anteriormente en el ATRQ).
    5. Pacientes con una puntuación total en MADRS ? 26 en las visitas de selección y basal.
    6. Pacientes dispuestos a suspender todos los medicamentos psicótropos prohibidos para satisfacer los periodos de lavado farmacológico exigidos antes y durante el periodo del estudio clínico.
    E.4Principal exclusion criteria
    For full details on exclusion criteria, please refer to Section 3.4.3 of teh trial protocol.
    - Subjects who report an inadequate response (less than 50% reduction in depressive symptom severity) to more than 3 antidepressant treatments during the current major depressive episode at a therapeutic dose (as defined by the ATRQ) and for an adequate duration (minimum duration of 6 weeks), including any antidepressant that the subject may be taking at screening if it meets the criteria for adequate treatment.
    - Subjects who report treatment with adjunctive antipsychotic medication with an antidepressant for a minimum of 3 weeks during the current major depressive episode.
    - Subjects who have received ECT for the current major depressive episode.
    - Subjects who have had an inadequate response to ECT at any time in the past or who have had a vagus nerve stimulation or deep brain stimulation device implanted for management of treatmentresistant depression.
    -Subjects with a current need for involuntary commitment or who have been hospitalized within 4 weeks of screening for the current major depressive episode.
    - Subjects with a current Axis I (DSM-IV-TR) diagnosis of:
    -- Delirium, dementia, amnestic or other cognitive disorder
    -- Schizophrenia, schizoaffective disorder, or other psychotic disorder
    -- Bipolar I disorder, bipolar II disorder, or bipolar disorder NOS
    -- Eating disorder (including anorexia nervosa or bulimia)
    -- Obsessive-compulsive disorder
    -- Panic disorder
    -- Posttraumatic stress disorder
    -Subjects with a current Axis II (DSM-IV-TR) diagnosis of borderline, antisocial, paranoid, schizoid, schizotypal or histrionic personality disorder, or mental retardation.
    - Subjects experiencing hallucinations, delusions or any psychotic symptomatology in the current major depressive episode.
    -Subjects who answer ?Yes? on the C-SSRS Suicidal Ideation Item 4 (Active Suicidal Ideation with Some Intent to Act, Without Specific Plan) and whose most recent episode meeting criteria for this C-SSRS Item 4 occurred within the last 6 months, OR
    Subjects who answer ?Yes? on the C-SSRS Suicidal Ideation Item 5 (Active Suicidal Ideation with Specific Plan and Intent) and whose most recent episode meeting criteria for this C-SSRS Item 5 occurred within the last 6 months OR
    Subjects who answer ?Yes? on any of the 5 C-SSRS Suicidal Behavior Items (actual attempt, interrupted attempt, aborted attempt, preparatory acts, or behavior) and whose most recent episode meeting criteria for any of these 5 C-SSRS Suicidal Behavior Items occurred within the last 2 years, OR
    Subjects who, in the opinion of the investigator, present a serious risk of suicide.
    - Subjects who have met DSM-IV-TR criteria for substance abuse or dependence within the past 180 days; including alcohol and benzodiazepines, but excluding nicotine dependence.
    -Pacientes que refieren una respuesta inadecuada (reducción menor del 50 % de la intensidad de los síntomas de depresión) a más de 3 tratamientos antidepresivos en dosis terapéutica (definida según el ATRQ) y con una duración adecuada (duración mínima de 6 semanas) durante el episodio depresivo mayor actual, incluidos los antidepresivos que haya podido tomar el paciente durante la fase de selección, si cumplen los criterios de tratamiento adecuado.
    - Pacientes que refieren tratamiento con un antipsicótico adyuvante junto a un antidepresivo durante al menos 3 semanas durante el episodio depresivo mayor actual.
    - Pacientes que refieren reacciones alérgicas o intolerancia (antecedentes de tratamiento en cualquier momento de su vida) a todos los antidepresivos proporcionados en el estudio que no se le han prescrito durante el episodio depresivo mayor (es decir, no se asignará un antidepresivo a los pacientes cuando hayan descrito problemas de intolerancia en algún otro momento).
    - Pacientes que han recibido TEC para su episodio depresivo mayor actual.
    Pacientes con respuesta inadecuada a la TEC en cualquier momento anterior o en los que se haya implantado un dispositivo para la estimulación del nervio vago o la estimulación cerebral profunda para el tratamiento de una depresión resistente al tratamiento.
    - Pacientes que necesiten actualmente un internamiento involuntario o que hayan sido hospitalizados en las 4 semanas anteriores a la selección debido al episodio depresivo mayor actual.
    - Pacientes con un diagnóstico actual de eje I (DSM-IV-TR) de:
    ? Delirio, demencia, amnesia u otro trastorno cognoscitivo
    ? Esquizofrenia, trastorno esquizoafectivo u otro trastorno psicótico
    ? Trastorno bipolar I, trastorno bipolar II o trastorno bipolar SOE
    ? Trastornos de la alimentación (entre ellos, anorexia nerviosa o bulimia)
    ? Trastorno obsesivo compulsivo
    ? Crisis de angustia
    ? Trastorno de estrés postraumático
    - Pacientes con un diagnóstico actual de Eje II (DSM-IV-TR) de trastorno de personalidad límite, antisocial, paranoide, esquizoide, esquizotípico o histriónico, o retraso mental.
    - Pacientes que hayan experimentado alucinaciones, delirios o alguna sintomatología psicótica durante el episodio depresivo mayor actual.
    - Pacientes que empiezan una psicoterapia (terapia individual, de grupo, de pareja o de familia) en los 42 días anteriores a la selección o en cualquier momento durante su participación en el estudio.
    - Pacientes con respuesta afirmativa en el elemento 4 de ideación suicida del C-SSRS (ideación suicida activa con algún intento práctico, sin un plan específico) y cuyo episodio más reciente que cumplió los criterios del elemento 4 del C-SSRS se haya producido en los últimos 6 meses, O
    - Pacientes con respuesta afirmativa en el elemento 5 de ideación suicida del C-SSRS (ideación suicida activa con un plan específico e intento de suicidio) y cuyo episodio más reciente que cumplió los criterios del elemento 5 del C-SSRS se haya producido en los últimos 6 meses, O
    Pacientes con respuesta afirmativa en el elemento 5 de ideación suicida del C-SSRS (intento actual, intento interrumpido, intento abortado, actos preparatorios o comportamiento suicida) y cuyo episodio más reciente que cumplió los criterios del elemento 5 del C-SSRS se haya producido en los últimos 2 años, O
    - Pacientes que, en opinión del investigador, presentan un riesgo grave de suicidio.
    Pacientes que han cumplido los criterios del DSM-IV-TR para drogodependencia en los últimos 180 días, incluidos el alcohol y las benzodiacepinas, pero no la dependencia de nicotina.
    E.5 End points
    E.5.1Primary end point(s)
    The primary outcome endpoint for determination of efficacy is
    the change from randomization to endpoint in the MADRS
    Total Score.
    El criterio principal de valoración para la determinación de la eficacia es la variación de la puntuación total de la MADRS desde la aleatorización hasta el final del estudio.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary endpoint will be evaluated at the end of treatment visit according to the blinded study design. The actual week when each individual subject will have their end of treatment visit is determined by the randomization system (IWRS) in a blinded manner.
    El criterio principal de valoracion será evaluado en la visita fin de estudio de acuerdo con el diseño ciego del estudio. La semana exacta de cuando los sujetos tendrán si visita fin de estudio viene determinda por el sistema de aleatorización (IWRS) de manera ciega.
    E.5.2Secondary end point(s)
    The key secondary efficacy endpoint is the change from randomization to endpoint in SDS Score (the mean of 3 individual item scores).
    El criterio de valoración secundario clave de la eficacia es la variación de la puntuación SDS (la media de 3 puntuaciones individuales) desde la aleatorización hasta el final del estudio.
    E.5.2.1Timepoint(s) of evaluation of this end point
    The secondary endpoint will be evaluated at the end of treatment visit according to the blinded study design. The actual week when each individual subject will have their end of treatment visit is determined by the randomization system (IWRS) in a blinded manner.
    El criterio de valoración secondario será evaluado en la visita fin de estudio de acuerdo con el diseño ciego del estudio. La semana exacta de cuando los sujetos tendrán si visita fin de estudio viene determinda por el sistema de aleatorización (IWRS) de manera ciega.
    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 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) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    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 concerned4
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    France
    Germany
    Poland
    Russian Federation
    Serbia
    Slovakia
    Spain
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The End of Trial Date is defined as the last Date of Contact or the Date of Final Contact Attempt from the Post-treatment Follow-up eCRF page for the last subject completing or withdrawing from the trial.
    La fecha de finalización del estudio clínico se define como la última fecha de contacto o la fecha del intento de contacto final de la página del CRDe de seguimiento posterior al tratamiento para el último paciente que complete el estudio clínico o se retire de él.
    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 months10
    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 months10
    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: 1286
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 54
    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
    Consent may be obtained from a legally accepted representative as permitted by national regulations and the appropriate IEC.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state60
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 500
    F.4.2.2In the whole clinical trial 1340
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Subjects may have the option to enter an open-label rollover trial after completion of treatment.
    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 Decision2013-10-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2013-10-09
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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