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    Summary
    EudraCT Number:2014-004586-24
    Sponsor's Protocol Code Number:ESKETINTRD3003
    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:2015-07-31
    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 number2014-004586-24
    A.3Full title of the trial
    A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression
    Estudio multicéntrico, aleatorizado, doble ciego y controlado con producto activo de esketamina intranasal más un antidepresivo oral para la prevención de las recaídas en depresión resistente al tratamiento.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
    Estudio de Esketamina intranasal más un antidepresivo oral para la prevención de las recaídas en participantes adultos en depresión resistente al tratamiento
    A.3.2Name or abbreviated title of the trial where available
    SUSTAIN-1
    A.4.1Sponsor's protocol code numberESKETINTRD3003
    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 SponsorJanssen-Cilag International NV
    B.1.3.4CountryBelgium
    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 supportJanssen Research & Development
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag S.A.
    B.5.2Functional name of contact pointGlobal Clinical Operations
    B.5.3 Address:
    B.5.3.1Street AddressPaseo de las Doce Estrellas, 5-7
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28042
    B.5.3.4CountrySpain
    B.5.4Telephone number3491722 8100
    B.5.5Fax number34917228628
    B.5.6E-mailagonza45@its.jnj.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 nameEsketamine - Nasal Solution - eq 140mg/mL esketamine base (eq 161.4 mg/mL esketamine HCl)
    D.3.4Pharmaceutical form Nasal spray, solution
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPNasal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNESKETAMINE Esketamine (for (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone)
    D.3.9.3Other descriptive nameESKETAMINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB25811
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number161.4
    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 Cymbalta 30 mg hard gastro-resistant capsules
    D.2.1.1.2Name of the Marketing Authorisation holderEli Lilly Nederland BV
    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.3.4Pharmaceutical form Gastro-resistant capsule, hard
    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 INNDULOXETINE HYDROCHLORIDE
    D.3.9.1CAS number 136434-34-9
    D.3.9.3Other descriptive nameDULOXETINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB20026
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number30
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP 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 CIPRALEX® 10 mg film-coated tablets
    D.2.1.1.2Name of the Marketing Authorisation holderH. Lundbeck A/S
    D.2.1.2Country which granted the Marketing AuthorisationDenmark
    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.3.4Pharmaceutical 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 INNESCITALOPRAM
    D.3.9.3Other descriptive nameESCITALOPRAM
    D.3.9.4EV Substance CodeSUB16425MIG
    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: 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 ZOLOFT
    D.2.1.1.2Name of the Marketing Authorisation holderPfizer
    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.3.4Pharmaceutical 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 INNSERTRALINE HYDROCHLORIDE
    D.3.9.3Other descriptive nameSERTRALINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB04375MIG
    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: 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 Trevilor® retard 75 mg hard, prolonged-release capsules
    D.2.1.1.2Name of the Marketing Authorisation holderPFIZER PHARMA GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Prolonged-release capsule, hard
    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 INNVENLAFAXINE HYDROCHLORIDE
    D.3.9.3Other descriptive nameVENLAFAXINE HYDROCHLORIDE
    D.3.9.4EV Substance CodeSUB05087MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 placeboNasal spray
    D.8.4Route of administration of the placeboNasal use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Treatment-resistant Major Depression
    Depresión resistente a tratamiento
    E.1.1.1Medical condition in easily understood language
    Depression is a mental disorder characterized by low mood and/or loss of interest or pleasure in nearly all activities.
    La depresión es un trastorno mental que se caracteriza por un bajo estado de
    ánimo y / o pérdida de interés o placer en casi todas las actividades.
    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 18.0
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of this study is to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in subjects with TRD who are in stable remission after an induction and optimization course of intranasal esketamine plus an oral antidepressant.
    El objetivo principal de este estudio es evaluar la eficacia de esketamina intranasal más un antidepresivo oral en comparación con un antidepresivo oral (comparador activo) más placebo intranasal para retrasar la reaparición de los síntomas depresivos en pacientes con DRT que se encuentran en remisión estable tras un ciclo de inducción y optimización de esketamina intranasal más un antidepresivo oral.
    E.2.2Secondary objectives of the trial
    -To assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in subjects with TRD with stable response (but who are not in stable remission) after an induction and optimization courseof intranasal esketamine plus an oral antidepressant.
    -To assess the effect of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo on various parameters (see protocol for details).
    - To investigate the safety and tolerability of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in subjects with TRD (see protocol for details)
    - Evaluar la eficacia de esketamina intranasal más un antidepresivo oral en comparación con un antidepresivo oral (comparador activo) más placebo intranasal para retrasar la reaparición de los síntomas depresivos en pacientes con DRT y respuesta estable (pero no en remisión estable) tras un ciclo de inducción y optimización de esketamina intranasal más un antidepresivo oral.
    - Evaluar el efecto de esketamina intranasal más un antidepresivo oral en comparación con un antidepresivo oral (comparador activo) más placebo intranasal en varios parámetos.
    - Investigar la seguridad y tolerabilidad de esketamina intranasal más un antidepresivo oral en comparación con un antidepresivo oral (comparador activo) más placebo intranasal en pacientes con DRT (Ver protocolo para más detalles)
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    For Direct-Entry Participants:
    - At the time of signing the informed consent form (ICF), participant must be a man or woman 18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than [>]18) to 64 years of age, inclusive

    - At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single episode MDD, the duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)

    - At the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (>=) 34

    - At the start of the screening/prospective observational phase, participants must have had nonresponse to >=2 but less than or equal to (<=) 5 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical history and pharmacy/prescription records, for the current episode of depression

    - The participant?s current major depressive episode and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be deemed valid for participation in a clinical study based on a Site-Independent Qualification Assessment For Transferred-Entry Participants

    - The participant must have completed the open-label induction phase in ESKETINTRD3001 or ESKETINTRD3002 and must have demonstrated response at the end of that phase (>=50% reduction in the MADRS total score from baseline [Day 1 pre-randomization] at the end of the 4-week double-blind induction phase)
    Para los participantes de entrada directa:
    - En el momento de firmar el documento de consentimiento informado (DCI), el participante debe ser un hombre o una mujer de 18 (o más, si la edad legal mínima de consentimiento en el país en el que el estudio se está realizando es mayor que [>] 18) a 64 años de edad, ambos inclusive.
    - Al comienzo de la fase de selección/observacional prospectiva, el participante debe cumplir los criterios diagnósticos del Manual Diagnóstico y Estadístico de los Trastornos Mentales (DSM-5) para de trastorno depresivo mayor (TDM) de episodio único (en caso de TDM de episodio único, la duración debe ser mayor o igual que [> =] 2 años) o trastorno depresivo mayor (TDM) recurrente, sin síntomas psicóticas, basándose en la evaluación clínica y confirmándose la Mini-entrevista neuropsiquiátrica internacional (MINI)
    - Al comienzo de la fase de selección/observacional prospectiva, el participante debe tener puntuación total mayor o igual que (>=) 34 en el Cuestionario de síntomas depresivos valorado por el médico (IDS-C30).
    - Al comienzo de la fase de selección/observacional prospectiva, los pacientes no deben haber respondido a >=2 pero <=5 antidepresivos orales tomados en una dosis adecuada y durante un período adecuado, según la evaluación del Cuestionario de respuesta al tratamiento antidepresivo del Massachusetts General Hospital (MGH-ATRQ) y documentado mediante la historia clínica/registros de farmacia o prescripción, en el episodio de depresión actual.
    - El episodio actual de depresión mayor del paciente y la respuesta a los tratamientos antidepresivos utilizados en dicho episodio (evaluados de manera retrospectiva) deben considerarse válidos para la participación en un estudio clínico basándose en la Evaluación de la calificación independiente del centro.
    Para pacientes transferidos:
    - El participante debe haber completado la fase de inducción abierta en ESKETINTRD3001 o ESKETINTRD3002 y debe haber demostrado respuesta al final de esa fase (>= 50% de reducción en la puntuación total de la MADRS al final de la fase de inducción doble ciego de 4 semanas, respecto el momento basal [día 1 pre-aleatorización]
    E.4Principal exclusion criteria
    - Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (ie, duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the current major depressive episode (based on MGH-ATRQ), or an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral ECT

    - Participant currently has an implant for vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression

    - Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis, bipolar or related disorders (confirmed by the MINI), comorbid obsessive compulsive disorder, intellectual disability (only DSM-5 diagnostic code 319), borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder

    - Participant has homicidal ideation/intent, per the investigator?s clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator?s clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)

    - Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
    -Participantes que han demostrado previamente falta de respuesta en los síntomas depresivos a esketamina o ketamina en el episodio actual de depresión mayor, a las 4 opciones de tratamiento antidepresivo orale disponibles para la fase de inducción doble ciego (es decir, duloxetina, escitalopram, sertralina y venlafaxina de liberación prolongada [XR]) en el episodio actual de depresión mayor (basado en MGH-ATRQ), o un ciclo adecuado de tratamiento con terapia electroconvulsiva (TEC) en el episodio actual de depresión mayor, definido como al menos 7 tratamientos con TEC unilateral.
    - Participante que presenta actualmente un implante para estimulación nerviosa vagal (ENV) o ha recibido estimulación cerebral profunda (ECP) en el episodio actual de depresión.
    - Participante que tiene un diagnóstico actual o previo según el DSM-5 de trastorno psicótico o TDM con psicosis, trastorno bipolar o trastornos relacionados (confirmado mediante la MINI), trastorno obsesivo compulsivo concomitante, discapacidad intelectual (sólo el código de diagnóstico 319 del DSM-5), trastorno límite de la personalidad, trastorno antisocial de la personalidad, trastorno histriónico de la personalidad o trastorno narcisista de la personalidad.
    - Participante que tiene ideación/intención homicida, según el criterio clínico del investigador, o tiene ideación suicida con alguna intención de actuar dentro de los 6 meses previos al comienzo de la fase de selección/observacional prospectiva, según el criterio clínico del investigador o en base a la Escala de valoración de la gravedad del comportamiento suicida de Columbia (C-SSRS).
    - Participantes con antecedentes de trastorno moderado o grave de abuso de sustancias psicoactivas o alcohol según los criterios del DSM-5.
    E.5 End points
    E.5.1Primary end point(s)
    Time to relapse in Participants with stable remission who were randomized in the maintenance phase
    Tiempo hasta la recaída en participantes con remisión estable que hayan sido aleatorizados en la fase de mantenimiento
    E.5.1.1Timepoint(s) of evaluation of this end point
    Time between participant randomization into the maintenance phase and the first documentation of a relapse event
    Tiempo entre la aleatorización del participante en la fase de mantenimiento y la primera documentación de un caso de recaída
    E.5.2Secondary end point(s)
    1) Time to relapse in Participants with Stable Response (but not in stable remission) who were randomized in the maintenance phase.
    2) Change From Baseline in MADRS total score at end of the Maintenance Phase in participants who were randomized in this phase.
    3) Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ-9) Total Score at End of the Maintenance Phase in participants who were randomized in this phase.
    4) Change From Baseline in Clinical Global Impression ? Severity (CGI-S) Score at End of Maintenance Phase in participants who were randomized in this phase.
    5) Change From Baseline in Subject-reported Generalized Anxiety Disorder (GAD-7) Score at End of Maintenance Phase in participants who were randomized in this phase.
    6) Change From Baseline in Subject-reported Health-related Quality of Life and Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) at End of Maintenance Phase in participants who were randomized in this phase.
    7) Change From Baseline in Sheehan Disability Scale (SDS) Total Score at End of Maintenance Phase in participants who were randomized in this phase.
    8) Number of Participants with Adverse Events (AEs) and Serious AEs.
    1) Tiempo hasta la recaída en participantes con respuesta estable (pero no en remisión estable) que se hayan aleatorizados en la fase de mantenimiento.
    2) Cambio en la puntuación total de la MADRS al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizados en esta fase.
    3) Cambio en la puntuación total en los síntomas depresivos utilizando el Cuestionario de salud del paciente- 9 ítems completado por el paciente (PHQ-9) al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizados en esta fase.
    4) Cambio en la puntuación en la Impresión Clínica Global – Gravedad al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizado en esta fase.
    5) Cambio en la puntuación de la Escala del trastorno de ansiedad generalizada completada por el paciente (GAD-7) al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizado en esta fase.
    6) Cambio en la calidad de vida relacionada con la salud y el estado de salud, referidos por el paciente empleando el EuroQol, de 5 dimensiones y 5 niveles (EQ-5D-5L), al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizado en esta fase.
    7) Cambio en la puntuación total de la Escala de la discapacidad de Sheehan (SDS) al final de la fase de mantenimiento respecto el momento basal, en los participantes que se hayan aleatorizado en esta fase.
    8) Número de participantes con eventos adversos (EA) y EA graves.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Time between participant randomization into the maintenance phase and the first documentation of a relapse event.
    2) Baseline and End of Maintenanace Phase.
    3) Baseline and End of Maintenance Phase.
    4) Baseline and End of Maintenance Phase.
    5) Baseline and End of Maintenance Phase.
    6) Baseline and End of Maintenance Phase.
    7) Baseline and End of Maintenance Phase.
    8) Screening up to End of Follow-up Phase (up to 2 weeks after last dose of study drug).
    1) Tiempo entre la aleatorización de participantes en la fase de mantenimiento y la primera documentación de un caso de recaída
    2) Momento basal y fin de la fase de mantenimiento
    3) Momento basal y fin de la fase de mantenimiento
    4) Momento basal y fin de la fase de mantenimiento
    5) Momento basal y fin de la fase de mantenimiento
    6) Momento basal y fin de la fase de mantenimiento
    7) Momento basal y fin de la fase de mantenimiento
    8) Fase de selección hasta final de la fase de seguimiento (hasta 2 semanas después de la última dosis del fármaco del estudio).
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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 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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA86
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Belgium
    Brazil
    Canada
    Czech Republic
    France
    Germany
    Hungary
    Italy
    Mexico
    Poland
    Spain
    Turkey
    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
    LVLS
    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 months1
    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 months1
    E.8.9.2In all countries concerned by the trial days8
    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: 498
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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 state14
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 208
    F.4.2.2In the whole clinical trial 498
    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 will be return to standard of care treatment following participation in the study.
    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 Decision2015-09-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2015-09-08
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-02-15
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