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    Summary
    EudraCT Number:2011-003850-26
    Sponsor's Protocol Code Number:31-11-284
    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:2011-12-07
    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 number2011-003850-26
    A.3Full title of the trial
    A Multicenter, Open-label Study to Assess Hospitalization Rates in Adult Subjects with Schizophrenia Treated Prospectively for 6 Months with Aripiprazole IM Depot Compared with 6-month Retrospective Treatment with Oral Antipsychotics in a Naturalistic Community Setting in Europe, Canada, and Asia.
    Estudio abierto y multicéntrico para evaluar las tasas de hospitalización en pacientes adultos con esquizofrenia tratados de forma prospectiva durante 6 meses con aripiprazol intramuscular de liberación retardada comparado con el tratamiento retrospectivo de 6 meses con antipsicóticos orales en un entorno naturalista en Europa, Canadá y Asia.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A study to evaluate the number of hospitalizations of adults with schizophrenia treated with the study drug aripiprazole IM depot for 6 months, compared to those that have been treated with oral antipsychotics over the last 6 months in Europe, Canada and Asia.
    Un estudio para evaluar el número de hospitalizaciones en adultos con esquizofrenia tratados con el medicamento del estudio, aripiprazol intramuscular de liberación retardada, durante 6 meses comparado con aquellos que han sido tratados con antipsicóticos orales durante los últimos 6 meses en Europa, Canadá y Asia.
    A.4.1Sponsor's protocol code number31-11-284
    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 and Commercialization, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCenterwatch
    B.5.2Functional name of contact pointClinical Trials
    B.5.3 Address:
    B.5.3.1Street Address10 Winthrop Square, 5th Floor
    B.5.3.2Town/ cityBoston, MA
    B.5.3.3Post code02110
    B.5.3.4CountryUnited States
    B.5.4Telephone number+1617-948-5100
    B.5.5Fax number+1617-948-5101
    B.5.6E-mailarrive@centerwatch.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 nameAripiprazole
    D.3.2Product code OPC-14597
    D.3.4Pharmaceutical form Lyophilisate for suspension for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntramuscular use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNARIPIPRAZOLE
    D.3.9.1CAS number 129722-12-9
    D.3.9.4EV Substance CodeSUB05564MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number400
    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 Abilify
    D.2.1.1.2Name of the Marketing Authorisation holderOtsuka Pharmaceutical Europe Ltd.
    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 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 INNARIPIPRAZOLE
    D.3.9.1CAS number 129722-12-9
    D.3.9.4EV Substance CodeSUB05564MIG
    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 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 Abilify
    D.2.1.1.2Name of the Marketing Authorisation holderOtsuka Pharmaceutical Europe Ltd.
    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 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 INNARIPIPRAZOLE
    D.3.9.1CAS number 129722-12-9
    D.3.9.4EV Substance CodeSUB05564MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number15
    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
    Schizophrenia
    Esquizofrenia
    E.1.1.1Medical condition in easily understood language
    Schizophrenia
    Esquizofrenia
    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 PT
    E.1.2Classification code 10039626
    E.1.2Term Schizophrenia
    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
    To compare inpatient psychiatric hospitalization rates (proportion of subjects with > or = 1 inpatient psychiatric hospitalization[s]) between the retrospective period Months 4-6 (Weeks -12 to -24) while on oral standard-of-care (SOC) antipsychotic treatment(s) and the prospective period Phase B Months 4-6 (Weeks 12 to 24) after the switch to aripiprazole IM depot.
    Comparar los porcentajes de hospitalización psiquiátrica (proporción de pacientes con 1 o más hospitalizaciones psiquiátricas continuas) entre los meses 4 a 6 del período retrospectivo (semanas -12 a -24) bajo tratamientos con antipsicóticos por vía oral realizados según práctica clínica habitual (standard-of-care, SOC) y los meses 4 a 6 del período prospectivo Fase B (semanas 12 a 24) después del cambio a aripiprazol intramuscular de liberación retardada.
    E.2.2Secondary objectives of the trial
    To further evaluate long-term safety and tolerability of aripiprazole IM depot.
    Evaluar más a fondo la seguridad y tolerabilidad a largo plazo del aripiprazol intramuscular de liberación retardada
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1)
    Subjects who are able to provide written informed consent. If the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) requires consent by a legally acceptable representative (LAR) in addition to the subject, all required consents must be obtained prior to the initiation of any protocol-required procedure.
    2)
    Male and female subjects 18 to 65 years of age, inclusive, at time of informed consent.
    3)
    Subjects with a current diagnosis of schizophrenia as defined by DSM-IV-TR criteria and a history of the illness for at least 1 year (12 months) prior to screening from a reliable source (eg, subject, family member, friend, caregiver, healthcare provider, or medical records).
    4)
    Subjects who in the investigator's judgment would benefit from extended treatment with a long-acting injectable formulation.
    5)
    Subjects who will be able to produce at least 7 months retrospective data by records or a reliable source, pertaining to all hospitalizations and interventions (psychiatric and nonpsychiatric).
    6)
    Subjects who have at least 1 inpatient psychiatric hospitalization in the 2 years (24 months) prior to screening, but have been managed as outpatients for the 4 weeks prior to signing the ICF and for the full duration of the screening period.
    7)
    Subjects must have been on oral antipsychotic treatment for the full 7 months prior to the screening phase.
    8)
    Subjects who showed response to antipsychotic treatment (other than clozapine), according to the investigator's opinion.
    9)
    In the investigator's opinion, subjects who are able to understand the nature of the trial and follow protocol requirements, including the prescribed dosage regimens, tablet ingestion, aripiprazole IM depot injection, and discontinuation of prohibited concomitant medications; who can read and understand the written word in order to complete subject-reported outcomes measures; and who can be reliably rated on assessment scales.
    1)Pacientes capaces de proporcionar el consentimiento informado por escrito. Si el Comité de revisión institucional o el Comité Ético independiente requiere el consentimiento por un representante legalmente aceptable además del paciente, deben obtenerse todos los consentimientos necesarios antes de iniciar cualquier procedimiento requerido por el protocolo.
    2)Pacientes de ambos sexos de 18 a 65 años de edad, ambas inclusive, en el momento de la firma del consentimiento informado.
    3)Pacientes con un diagnóstico actual de esquizofrenia, según la definición de los criterios del DSM-IV-TR y antecedentes de la enfermedad durante al menos 1 año (12 meses) antes de la selección, procedentes de una fuente fiable (p. ej., el paciente, un familiar, amigo, cuidador, profesional sanitario o registros médicos).
    4)Pacientes que, según el criterio del investigador, podrían obtener beneficios de un tratamiento prolongado con una formulación inyectable de acción prolongada.
    5)Pacientes que puedan proporcionar datos retrospectivos de al menos 7 meses, mediante registros o una fuente fiable, referentes a todas las hospitalizaciones e intervenciones (psiquiátricas y no psiquiátricas).
    6)Pacientes que hayan tenido al menos 1 hospitalización psiquiátrica continua en los 2 años (24 meses) anteriores a la selección, pero que hayan recibido tratamiento de forma ambulatoria durante las 4 semanas anteriores a la firma del FCI y durante todo el período de selección.
    7)Los pacientes deben haber estado en tratamiento con antipsicóticos por vía oral durante los 7 meses completos antes de la fase de selección.
    8)Pacientes que, en opinión del investigador, hayan mostrado respuesta al tratamiento antipsicótico (diferente a la clozapina).
    9)Pacientes capaces, en opinión del investigador, de comprender la naturaleza del ensayo y cumplir los requisitos del protocolo, incluyendo las pautas posológicas prescritas, la toma de comprimidos, la inyección intramuscular de aripiprazol de liberación retardada y la interrupción de los medicamentos concomitantes prohibidos; capaces también de leer y comprender textos escritos para poder rellenar los cuestionario autoaplicables y poder dar una puntuación fiable en las escalas de evaluación.
    E.4Principal exclusion criteria
    1)
    Prisoners or subjects who are compulsorily detained (involuntarily incarcerated), or have been incarcerated in the past 7 months for any reason must not be enrolled into this trial.
    2)
    Subjects who may require potent CYP2D6 or CYP3A4 inhibitors or CYP3A4 inducers during the trial.
    3)
    Any subject who requires or may need any other antipsychotic medications during the course of the trial, other than allowed rescue medication.
    4)
    Subjects who are known to be allergic, intolerant, or unresponsive to prior treatment with aripiprazole or other quinolinones.
    5)
    Subjects with a history of hypersensitivity to antipsychotic agents.
    6)
    Subjects deemed intolerant of receiving injectable treatment.
    7)
    Subjects who have received electroconvulsive therapy within the last 7 months prior to screening.
    8)
    Subjects with a history of neuroleptic malignant syndrome or clinically significant tardive dyskinesia as assessed by the investigator.
    9)
    Subjects with a current DSM-IV-TR diagnosis other than schizophrenia, including schizoaffective disorder, major depressive disorder, bipolar disorder, delirium, dementia, amnestic or other cognitive disorders. Also, subjects with borderline, paranoid, histrionic, schizotypal, schizoid, or antisocial personality disorder.
    10)
    Subjects requiring hospitalization for any psychiatric reason during the 4 weeks prior to signing the ICF or during the screening period.
    11)
    Subjects without at least 1 inpatient psychiatric hospitalization in the last 2 years (24 months) prior to screening.
    12)
    Subjects who have met DSM-IV-TR criteria for any significant substance use disorder within 3 months prior to screening.
    13)
    Subjects who are considered treatment-resistant to antipsychotic medication other than clozapine.
    14)
    Treatment with long-acting injectable antipsychotics (eg, haloperidol decanoate, fluphenazine decanoate, risperidone long-acting injection [Risperdal® Consta®], paliperidone palmitate extended-release injectable suspension [Invega® Sustenna®], olanzapine for extended-release injectable suspension [Zyprexa® Relprevv®]), in which the last dose was within 7 months prior to screening.
    15)
    Subjects who have not been treated with oral antipsychotics for 7 months prior to screening.
    16)
    Subjects who have a significant risk of committing suicide based on history, routine psychiatric status examination, investigator's judgment, or who have an answer of "yes" on questions 4 or 5 (current or over the last 30 days) on the baseline version of the Columbia Suicide Severity Rating Scale (C-SSRS).
    17)
    Subjects who have a history or evidence of a medical condition that would expose them to an undue risk of a significant adverse event or interfere with assessments of safety or efficacy during the course of the trial, including but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, neurologic, hematologic, or immunologic disease as determined by the clinical judgment of the investigator.
    18)
    Sexually active males who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 180 days following the last dose of trial medication, or sexually active females of childbearing potential who will not commit to utilizing 2 of the approved birth control methods or who will not remain abstinent during the trial and for 150 days following the last dose of trial medication. Abstinence will be permitted if it is confirmed and documented at every trial visit. If employing birth control, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pill, birth control depot injections, implant, condom or sponge with spermicide. Note: Women of child bearing potential (WOCBP) is defined as all women unless they have had an oophorectomy and/or hysterectomy or have been menopausal for 12 consecutive months.
    19)
    The following laboratory test, vital sign, and electrocardiogram (ECG) results are exclusionary:
    a) Platelets < or = 75,000/mm3
    b) Hemoglobin < or = 9 g/dL
    c) Neutrophils, absolute < or = 1000/mm3
    d) Aspartate aminotransferase (AST) > 3x upper limit of normal
    e) Alanine aminotransferase (ALT) > 3x upper limit of normal
    f) Creatinine > or = 2 mg/dL
    g) Diastolic blood pressure > 105 mm Hg
    h) QTc > 475 msec on either the QTcB (Bazett) or QTcF (Fridericia) corrections on 2 out of 3 time points of ECGs performed (based on the report by the central service).
    20)
    Subjects who have previously enrolled in an aripiprazole IM depot clinical study.
    21)
    Subjects who have participated in any clinical trial with an investigational agent within the past 30 days.
    1)No se incluirán prisioneros o pacientes detenidos obligatoriamente, o que hayan estado encarcelados en los últimos 7 meses por cualquier causa.
    2)Pacientes que puedan requerir el uso de inhibidores potentes de CYP2D6 o de CYP3A4, o de inductores de CYP3A4 durante el ensayo.
    3)Cualquier paciente que requiera o pueda requerir cualquier otro antipsicótico durante el ensayo, salvo los de rescate permitidos.
    4)Pacientes que se sepa son alérgicos, intolerantes o que no respondieron a los tratamientos previos con aripiprazol u otras quinolinonas.
    5)Pacientes con antecedentes de hipersensibilidad a los agentes antipsicóticos.
    6)Pacientes considerados intolerantes a los tratamientos inyectables.
    7)Pacientes que hayan recibido tratamiento electroconvulsivo en los 7 meses inmediatamente anteriores a la selección.
    8)Pacientes con antecedentes de síndrome neuroléptico maligno o de discinesia tardía clínicamente importante, según la evaluación del investigador.
    9)Pacientes con un diagnóstico actual (según el DSM-IV-TR) diferente al de esquizofrenia, incluido trastorno esquizoafectivo, trastorno depresivo mayor, trastorno bipolar, delirio, demencia, amnesia u otros trastornos cognitivos. Además, pacientes con trastorno de personalidad límite, paranoide, histriónico, esquizotípico, esquizoide o antisocial.
    10)Pacientes que hayan requerido hospitalización por cualquier causa psiquiátrica durante las 4 semanas antes de la firma del FCI o durante el período de selección.
    11)Pacientes sin al menos 1 hospitalización psiquiátrica continua en los 2 años anteriores a la selección.
    12)Pacientes que cumplan con los criterios del DSM-IV-TR de abuso de sustancias tóxicas en los 3 meses previos a la selección.
    13)Pacientes que se consideren resistentes al tratamiento con medicamentos antipsicóticos diferentes a la clozapina.
    14)Tratamiento con antipsicóticos inyectables de acción prolongada (p. ej., decanoato de haloperidol, decanoato de flufenazina, risperidona en inyección de acción prolongada [Risperdal® Consta®], suspensión inyectable de palmitato de paliperidona de liberación extendida [Invega® Sustenna®], suspensión inyectable de liberación retardada de olanzapina [Zyprexa® Relprevv?]), cuya última dosis se haya administrado en los 7 meses previos a la selección.
    15)Pacientes que no hayan recibido tratamiento con antipsicóticos por vía oral durante los 7 meses antes de la selección.
    16)Pacientes con riesgo importante de suicidio según sus antecedentes, el examen habitual de su estado psiquiátrico, el criterio del investigador o que hayan respondido afirmativamente a las preguntas 4 o 5 (en ese momento o durante los 30 días anteriores) de la versión inicial de la Escala de puntuación de la intensidad de la intención suicida de Columbia (C-SSRS).
    17)Pacientes con antecedentes o pruebas de una afección médica que podría exponerlos a un riesgo inaceptable de sufrir un acontecimiento adverso importante o interferir con las evaluaciones de seguridad o eficacia durante el ensayo, tales como, hepatopatías, nefropatías, enfermedades respiratorias, cardiovasculares, endocrinas, neurológicas, hematológicas o inmunológicas, según el criterio clínico del investigador.
    18)Hombres sexualmente activos que no se comprometan a usar dos de los métodos anticonceptivos aprobados o que no mantengan abstinencia durante el ensayo y durante los 180 días siguientes a la última dosis de medicamento del estudio, o mujeres sexualmente activas en edad de procrear que no se comprometan a usar dos de los métodos anticonceptivos aprobados o que no guarden abstinencia durante el ensayo y durante los 150 días siguientes a la última dosis de medicamento del estudio. Se permitirá la abstinencia si puede confirmarse y documentarse en todas las visitas del ensayo. Si se utilizan los métodos anticonceptivos, deben usarse dos de las siguientes precauciones: vasectomía, ligadura de trompas, diafragma vaginal, dispositivo intrauterino, píldora anticonceptiva, inyecciones anticonceptivas de liberación retardada, implante anticonceptivo, preservativo o esponja con espermicida.
    19)Son causa de exclusión los siguientes resultados de los análisis de laboratorio, constantes vitales y electrocardiograma (ECG):
    a)Trombocitos <o= 75.000/mm3
    b)Hemoglobina <o= 9 g/dl
    c)Neutrófilos, recuento absoluto <o= 1000/mm3
    d)Aspartato aminotransferasa (AST) > 3 veces el límite superior de lo normal
    e)Alanina aminotransferasa (ALT) > 3 veces el límite superior de lo normal
    f)Creatinina >o = 2 mg/dl
    g)Presión arterial diastólica > 105 mmHg
    h)QTc > 475 ms ya sea con las correcciones QTcB (de Bazett) o QTcF (de Fridericia) en 2 resultados de los 3 ECG realizados (basándose en el informe del servicio central).
    20)Pacientes que hayan participado previamente en un estudio clínico con aripiprazol intramuscular de liberación retardada.
    21)Pacientes que hayan participado en cualquier ensayo clínico con un medicamento en investigación en los últimos 30 días.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy: The primary endpoint of this trial is the comparison of inpatient psychiatric hospitalization rates (proportion of subjects with > or = 1 inpatient psychiatric hospitalization[s]) between the retrospective period Months 4-6 (Weeks -12 to -24) while on oral SOC antipsychotic treatment and the prospective period Phase B Months 4-6 (Weeks 12 to 24) after switch to aripiprazole IM depot.
    Eficacia: El objetivo principal de este ensayo es comparar las tasas de hospitalización psiquiátrica continua (proporción de sujetos con 1 o más hospitalizaciones psiquiátricas continuas) entre los meses 4 a 6 del período retrospectivo (semanas -12 a -24) bajo tratamiento antipsicótico por vía oral según la SOC y los meses 4 a 6 del período prospectivo en Fase B (semanas 12 a 24) después del cambio a aripiprazol intramuscular de liberación retardada.
    E.5.1.1Timepoint(s) of evaluation of this end point
    The analysis will be performed using a McNemar test on those who have hospitalization data during months 4-6 prior to the 4-week outpatient treatment period before study entry and during months 4-6 after switch to aripiprazole IM depot.
    Please see protocol for more details.
    El análisis se llevará a cabo mediante una prueba de McNemar sobre los pacientes que tengan datos de hospitalización durante los meses 4 a 6 anteriores al período de tratamiento ambulatorio de 4 semanas antes de la incorporación al estudio y durante los meses 4 a 6 después del cambio a aripiprazol intramuscular de liberación retardada.
    Véase el protocolo para mayor información.
    E.5.2Secondary end point(s)
    The last 3 months of the retrospective and prospective (Phase B) treatment periods will be compared in the analysis of the following endpoints:
    - Number of inpatient psychiatric hospitalizations per subject.
    - Cumulative duration of inpatient psychiatric hospitalizations.
    - Mean duration of inpatient psychiatric hospitalizations.
    - Number and mean duration of all other (non-inpatient) psychiatric treatment visits including, but not limited to, partial hospitalizations, intensive outpatient programs, assertive community treatment programs, emergency room visits, hospitalizations for psychosocial reasons, etc.
    - Number of inpatient nonpsychiatric hospitalizations per subject.
    - Cumulative duration of inpatient nonpsychiatric hospitalizations.
    - Mean duration of inpatient nonpsychiatric hospitalizations.
    - Number and mean duration of all other (outpatient or non-inpatient) nonpsychiatric treatment visits including, but not limited to, emergency room visits.

    In addition, the following endpoints will be assessed in Phase B:
    - Mean change from baseline (Day 0) to Week 24 in PANSS total score.
    - Mean change from baseline (Day 0) to Week 24 in PANSS positive and negative subscale scores.
    - Mean change from baseline (Day 0) to Week 24 in CGI-S score.
    - Mean CGI-I score at Week 24.
    - Discontinuation rate due to all causes.
    - Time to discontinuation due to all causes.
    - Proportion of responders (ie, defined as > or = 30% decrease from baseline in PANSS total score or a score of 1 [very much improved] or 2 [much improved] on the CGI-I scale).
    - Mean change from baseline (Day 0) to Week 24 in QLS score.
    - Mean change from baseline (Day 0) to Week 24 in SWN-S score.
    - Mean change from baseline (Day 0) to Week 24 in DAI total score.
    - Mean change from baseline (Day 0) to Week 24 in IWQoL-Lite total score.
    - Mean change from baseline (Day 0) to Week 24 in IAQ total score.

    Safety Endpoints:
    Adverse events will be examined by frequency, severity, seriousness, and discontinuation (all cause and due to AEs). The Columbia Suicide Severity Rating Scale (C-SSRS) will be completed at baseline and all subsequent visits to assess the risk of suicide events and to classify reported suicide events. Injection site pain will be assessed by mean visual analogue scale (VAS) scores as reported by the subject after each injection in Phase B.
    The investigator rating of localized pain, redness, swelling, and induration at the injection site will also be tabulated.
    The incidence of clinically significant changes will be calculated for vital signs and routine laboratory tests. Mean change from baseline and incidence of clinically significant changes will be calculated for ECG parameters, prolactin concentrations, lipid/metabolic profile (fasting glucose, fasting total cholesterol, fasting high density lipoprotein (HDL), fasting low density lipoprotein (LDL), fasting triglycerides) and body weight. A central ECG service will be utilized to review all ECGs in order to standardize interpretations for the safety analysis. Extrapyramidal symptoms will be evaluated by calculating mean change from baseline in the Simpson-Angus Scale (SAS), Abnormal Involuntary Movement Scale (AIMS), and Barnes Akathisia Rating Scale (BARS). By-subject listings of physical examination findings will be reviewed as a further assessment of safety.
    En el análisis de los siguientes objetivos Se compararán los últimos 3 meses de los períodos de tratamiento retrospectivo y prospectivo (Fase B) para los siguientes criterios de valoración:
    - Cantidad de hospitalizaciones psiquiátricas
    por paciente.
    - Duración acumulada de las hospitalizaciones psiquiátricas.
    - Duración media de las hospitalizaciones psiquiátricas.
    - Cantidad y duración media de todas las demás visitas de tratamiento psiquiátrico (no hospitalizaciones), entre otras, las hospitalizaciones parciales, programas intensivos como paciente externo, programas de tratamiento asertivo comunitario, visitas a salas de urgencias, hospitalizaciones por causas psicosociales, etc.
    - Cantidad de hospitalizaciones no psiquiátricas por paciente.
    - Duración acumulada de las hospitalizaciones no psiquiátricas.
    - Duración media de las hospitalizaciones no psiquiátricas.
    - Cantidad y duración media de todas las demás visitas de tratamiento no psiquiátrico (como paciente externo o no hospitalizado), entre otras, las visitas a salas de urgencias.

    Además, en la Fase B se evaluarán los siguientes criterios
    de valoración:
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación total de la PANSS.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en las puntuaciones de las subescalas positiva y negativa de la PANSS.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación de la CGI-S.
    - Puntuación media de la CGI-I en la semana 24.
    - Tasas de abandono por cualquier causa.
    - Tiempo transcurrido hasta el abandono por cualquier causa.
    - Proporción de pacientes con respuesta al tratamiento (es decir, definida como >o= 30 % de disminución con respecto a la visita inicial en la puntuación total de la PANSS o una puntuación de 1 [extremadamente mejorado] o 2 [muy mejorado] en la escala CGI-I).
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación de la QLS.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación de la SWN-S.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación total del DAI.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación total de la IWQoL-Lite.
    - Cambio medio desde la visita inicial (Día 0) hasta la semana 24 en la puntuación total del IAQ.

    Seguridad:
    Los acontecimientos adversos se examinarán por frecuencia, gravedad, intensidad y abandono (por cualquier causa y debido a AA). Se administrará la C-SSRS en la visita inicial y en todas las visitas posteriores para evaluar el riesgo de aparición de episodios suicidas y para clasificar los episodios de suicidio comunicados.
    Se calculará la incidencia de los cambios clínicamente importantes en las constantes vitales y en los análisis de laboratorio habituales. Se calculará el cambio medio con respecto a la visita inicial y la incidencia de cambios clínicamente importantes para los parámetros electrocardiográficos, las concentraciones de prolactina, el perfil lipídico/metabólico (glucemia en ayunas, colesterol total en ayunas, lipoproteína de alta densidad [HDL] en ayunas, lipoproteína de baja densidad [LDL] en ayunas, triglicéridos en ayunas) y el peso corporal. Para normalizar las interpretaciones para el análisis de seguridad, se utilizará un servicio de electrocardiografía central para revisar todos los ECG. Los SEP se evaluarán mediante el cálculo del cambio medio con respecto a la visita inicial en la SAS, AIMS y BARS cuando proceda. El dolor en el lugar de la inyección se evaluará mediante las puntuaciones medias VAS comunicadas por el paciente después de cada inyección y en todas las visitas del estudio. La puntuación del investigador de dolor localizado, enrojecimiento, hinchazón e induración en el lugar de la inyección también se obtendrá en evaluaciones posteriores a la inyección en todas las visitas. Como evaluación adicional de la seguridad, se revisarán los listados de los hallazgos de las exploraciones físicas de todos los pacientes.
    E.5.2.1Timepoint(s) of evaluation of this end point
    For a complete schedule of assessments please see the following tables in the protocol:
    - Table 3.6.1 (Screening and phase A)
    - Table 3.6.2 (Phase B)
    - Table 3.6.3 (Phase C)
    Para un calendario completo de las evaluaciones por favor, consulte las siguientes tablas en el protocolo
    - Tabla 3.6 1 (Selección y Fase A)
    - Tabla 3.6 2 (Fase B)
    - Tabla 3.6 3 (Fase C)
    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 No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Quality of life
    Calidad de vida
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 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 concerned15
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA95
    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
    Bulgaria
    France
    Germany
    Italy
    Poland
    Spain
    United Kingdom
    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 fin del ensayo se define como la última fecha de contacto o la fecha del intento de contacto final consignada en la página de seguimiento posterior al tratamiento del eCRF para el último paciente que finalice el ensayo o se retire de él.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months1
    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: 600
    F.1.3Elderly (>=65 years) No
    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 state225
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 450
    F.4.2.2In the whole clinical trial 600
    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)
    Standard of care.
    Tratamiento estándar o de referencia.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2012-03-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2012-02-09
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
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