Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36811   clinical trials with a EudraCT protocol, of which   6078   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2016-003990-17
    Sponsor's Protocol Code Number:54135419SUI3001
    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:2017-05-18
    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 number2016-003990-17
    A.3Full title of the trial
    A Double-blind, Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Subjects Assessed to be at Imminent Risk for Suicide
    Estudio doble ciego, aleatorizado, controlado con placebo para evaluar la eficacia y la seguridad de la esketamina intranasal, además del tratamiento integral según la práctica habitual, para la reducción rápida de los síntomas del trastorno depresivo
    mayor, incluida la ideación suicida, en pacientes adultos evaluados con riesgo inminente de suicidio.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study of the Efficacy and Safety of Intranasal Esketamine in the Rapid Reduction of Symptoms of Major Depressive Disorder, in Adults at Imminent Risk for Suicide
    Estudio de la eficacia y la seguridad de la esketamina intranasal en la reducción rápida de los síntomas del trastorno depresivo mayor, en adultos con riesgo inminente de suicidio.
    A.4.1Sponsor's protocol code number54135419SUI3001
    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 Internacional 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 Spain
    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 number34917228100
    B.5.5Fax number34917229628
    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 (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 number140
    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
    Major Depressive Disorder with Imminent Risk of Suicide
    Trastorno Depresivo Mayor con riesgo inminente de suicidio
    E.1.1.1Medical condition in easily understood language
    Depression with Risk of Suicide
    Depresión con riesgo de suicidio
    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 20.0
    E.1.2Level PT
    E.1.2Classification code 10042458
    E.1.2Term Suicidal ideation
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10012397
    E.1.2Term Depression suicidal
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10065604
    E.1.2Term Suicidal behaviour
    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 is to evaluate the efficacy of intranasal esketamine 84 mg compared with intranasal placebo in addition to comprehensive standard of care in reducing the symptoms of MDD, including suicidal ideation, in subjects who are assessed to be at imminent risk for suicide, as measured by the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose.
    El objetivo principal es evaluar la eficacia de esketamina intranasal 84 mg, en comparación con placebo intranasal, junto con la asistencia integral convencional en la reducción de los síntomas del TDM, incluida la ideación suicida, en sujetos
    considerados en riesgo de suicidio inminente, según lo determinado por la variación respecto al momento basal en la puntuación total en la escala de evaluación de la depresión de Montgomery-Asberg (MADRS) a las 24 horas de la primera dosis.
    E.2.2Secondary objectives of the trial
    The key secondary objective is to assess the efficacy of intranasal esketamine compared with intranasal placebo in reducing severity of suicidality as measured by the clinical global impression of severity of suicidality revised version (CGI-SS-R) at 24 hours post first dose. Other secondary objectives are listed in Protocol Section 2.1.1.
    El objetivo secundario fundamental es evaluar la eficacia de esketamina intranasal en comparación con placebo intranasal en la reducción de la intensidad del riesgo de suicidio, evaluada mediante la escala de impresión clínica global de la intensidad del riesgo de suicidio, versión revisada (CGI-SS-R), a las 24 horas de la primera dosis. Otros objetivos secundarios están listados en la sección 2.1.1 del Protocolo
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject must be a man or woman, 18 to 64 years of age, inclusive.
    2. Subject must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for MDD, without psychotic features, based upon clinical assessment and confirmed by the MINI.
    3. Subjects must have current suicidal ideation with intent, confirmed by a “Yes” response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] AND Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI. Note: the response to B3 must refer to the present, whereas the response to B10 may reflect the past 24 hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of MINI must be repeated prior to randomization to confirm eligibility.
    4. In the physician’s opinion, acute psychiatric hospitalization is clinically warranted due to subject’s imminent risk of suicide.
    5. Subject has a MADRS total score of >28 predose on Day 1.
    6. As part of standard of care treatment, subject agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator’s opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25).
    7. Subject is comfortable with self-administration of intranasal medication and able to follow instructions provided.
    8. Subject must be medically stable on the basis of physical examination, medical history, vital signs, and 12-lead ECG performed at screening. If there are abnormalities, the subject may be included only if the investigator judges the abnormalities to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator.
    9. Subject must be medically stable on the basis of clinical laboratory tests performed by the local laboratory at screening. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant. This determination must be recorded in the subject's source documents and initialed by the investigator.
    10. Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for subject participating in clinical studies.
    Before randomization, a woman must be either:
    a. Not of childbearing potential defined as:
    -postmenopausal (>45 years of age with amenorrhea for at least 12 months), permanently sterilized (eg, bilateral tubal occlusion/ligation procedures, hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy
    b. Of childbearing potential and
    -practicing a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly)
    -agrees to use a highly effective method throughout the study and for at least 6 weeks after the last dose of study drug.
    11. A woman of childbearing potential must have a negative urine pregnancy test at screening.
    12. During the study (ie, from Day 1 of the double-blind phase) and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study drug, a man who is sexually active with a woman of childbearing potential
    -must be practicing a highly effective method of contraception with his female partner
    -must use a condom if his partner is pregnant.
    -must agree not to donate sperm.
    Note: If the childbearing potential changes after start of the study, a female partner of a male study subject must begin a highly effective method of birth control.
    13. Subject must be willing and able to adhere to the prohibitions and restrictions specified in this protocol.
    14. Each subject must sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study.
    Note: Subjects with acute alcohol intoxication should not be screened (but can be screened once sober).
    15. Each subject must sign a separate informed consent form if he or she agrees to provide an optional DNA sample for research (where local regulations permit). Refusal to give consent for the optional DNA research sample does not exclude a subject from participation in the study.

    Additional information on inclusion criteria is found in Protocol Section 4.1
    1.Los sujetos deben ser varones o mujeres, de 18 a 64 años de edad
    2.El sujeto debe cumplir los criterios de diagnóstico para el TDM del Manual diagnóstico y estadístico de trastornos mentales (5ª edición) (DSM-5), sin características psicóticas según la evaluación clínica y con confirmación mediante la MINI
    3.Los sujetos deben tener ideación suicida con intención en la actualidad, confirmada por una respuesta “Sí” a la pregunta B3 [Pensar (aunque sea de forma pasajera) en hacerse daño o lesionarse a sí mismo: con al menos cierta intención o consciencia de que podría morir como resultado; o pensar en suicidarse (es decir, en quitarse la vida)] Y a la pregunta B10 [Intención de llevar a la práctica el pensamiento de quitarse la vida] en la MINI. Nota: la respuesta a B3 debe referirse al presente, mientras que la respuesta a B10 puede reflejar las últimas 24 horas. Si el período de selección es superior a 24 horas, la evaluación de B3 y B10 de la MINI deberán repetirse antes de la aleatorización para confirmar la elegibilidad
    4.En opinión del médico, está clínicamente justificada la hospitalización psiquiátrica aguda debido al riesgo de suicidio inminente del sujeto
    5.El sujeto tiene una puntuación total en la MADRS>28 antes de la administración el día 1
    6.Como parte de la asistencia convencional, el sujeto acepta voluntariamente ser hospitalizado durante un período recomendado de 5 días tras la aleatorización (puede ser más corto o más prolongado si está clínicamente justificado) y recibir el tratamiento/s antidepresivos no experimentales prescritos durante al menos todo el período de la fase de
    tratamiento doble ciego (día 25)
    7.El sujeto está cómodo con la autoadministración de la medicación intranasal y es capaz de seguir las instrucciones proporcionadas
    8.El sujeto debe encontrarse médicamente estable según la exploración física, la historia clínica, las constantes vitales y y el ECG de 12 derivaciones realizados durante la selección. Si hay anomalías, el sujeto podría ser incluido sólo si a criterio del investigador estas no son clínicamente significativas. Esta decisión debe recogerse en los documentos fuente del sujeto y registrarse con las iniciales del investigador
    9.El sujeto debe encontrarse médicamente estable según los análisis clínicos efectuados durante la selección. Si los resultados de la bioquímica sérica, hematología, o análisis de orina se encuentran fuera del rango de referencia
    normal, se podrá incluir al paciente únicamente si el investigador considera que las anomalías o desviaciones de la normalidad no son clínicamente significativas. Esta decisión debe recogerse en los documentos fuente del sujeto y registrarse con las iniciales del investigador.
    10.El uso de métodos anticonceptivos por hombres y mujeres debe ser conforme a las regulaciones locales, en relación al uso de métodos anticonceptivos para los sujetos participantes en ensayos clínicos. Antes de la aleatorización, una mujer debe ser: a.No potencialmente fértil, definido como:
    -postmenopáusica (>45 años con amenorrea durante al menos 12 meses), estéril de forma permanente (p.ej. los procedimientos bilaterales de oclusión/ ligadura de trompas, histerectomía, salpingectomía bilateral, ovariectomía bilateral), o de otra forma ser incapaz de concebir b.O tener capacidad de procrear y
    - utilizar un método anticonceptivo muy eficaz (tasa de fallos<1% al año cuando se usa de forma constante y correcta)
    - comprometerse a usar un método anticonceptivo muy eficaz durante todo el estudio y al menos en las seis semanas siguientes a la última dosis del fármaco del estudio 11.Una mujer potencialmente fértil debe dar negativo al test de embarazo de orina durante la selección
    12.Durante el estudio (es decir, desde el día 1 del período doble ciego) y durante un mínimo de un ciclo de
    espermatogénesis (definido como 90 días aprox.) después de recibir la última dosis de la medicación intranasal del estudio, un hombre que es sexualmente activo con una mujer potencialmente fértil -debe utilizar un método anticonceptivo muy eficaz con su pareja femenina -debe usar un condón si su pareja está embarazada -debe
    comprometerse a no donar semen
    13.El sujeto será capaz de cumplir todas las prohibiciones y limitaciones especificadas en este protocolo y estará dispuesto a cumplirlas
    14.Los sujetos deberán firmar un documento de consentimiento Informado (DCI) que indique que entienden el objetivo del estudio y los procedimientos que exige y que están dispuestos a participar en él
    15.Cada sujeto debe firmar un documento de consentimiento informado por separado si acepta aportar una muestra opcional de ADN para investigación (cuando la regulación local lo permita). El reusar a dicha aportación no excluye al sujeto de su participación en el estudio
    *Ver Sección 4.1 del Protocol para información adicional
    sobre criterios de inclusión
    Destinatario
    E.4Principal exclusion criteria
    1. Subject has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder.
    2. Subject currently meets DSM-5 criteria for borderline personality disorder.
    -Subjects not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded.
    3. Subject has a current clinical diagnosis of autism, dementia, or intellectual disability.
    4. Subject has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features.
    5. Subject has a history of moderate or severe substance or alcohol use disorder, according to DSM-5 criteria, except nicotine or caffeine, within 6 months before screening.
    6. Criterion modified per Amendment 1
    6.1. Subject has any of the following conditions:
    -a history or current signs and symptoms of liver or renal insufficiency
    -clinically significant cardiac (including unstable coronary artery disease and congestive heart failure, tachyarrhythmias and recent myocardial infarction) or vascular, pulmonary, gastrointestinal, endocrine (including uncontrolled hyperthyroidism), neurologic (including current or past history of seizures except uncomplicated childhood febrile seizures with no sequelae), hematologic, rheumatologic, or metabolic (including
    severe dehydration/hypovolemia) disease.
    7. Criterion modified per Amendment 1
    7.1. Subject has uncontrolled hypertension (systolic blood pressure
    >140 mmHg or diastolic blood pressure >90 mmHg) despite diet, exercise or a stable dose of anti-hypertensive treatment for at least 2 weeks at screening; or any past history of hypertensive crisis.
    -Subjects with conditions in which the elevation of blood pressure could be a serious risk (including unstable heart failure, severe cardiovascular disease, recent cerebral injury, increased intracranial pressure / intracranial mass lesion, intracranial bleeding or acute stroke, untreated glaucoma or perforating eye injury) are excluded.
    -An abnormal blood pressure value at screening can be repeated once after 5 minutes of relaxation for subject eligibility. On Day 1 of the double-blind phase prior to randomization, a supine or semi-supine systolic blood pressure >140 mmHg or diastolic blood pressure >90 mmHg is exclusionary.
    8. Subject has a positive urine test result(s) for phencyclidine (PCP), cocaine, or amphetamines at screening.
    -Subjects who have a positive test due to the appropriate use of prescribed opiates, benzodiazepines, or barbiturates may be eligible for study participation per clinician judgment. In addition, subjects who have a positive test for opiates, benzodiazepines, or barbiturates used without a prescription, may be considered eligible per clinician judgment and in consultation with the sponsor’s medical monitor.
    -Subjects who have a positive test due to opiates, benzodiazepines, or barbiturates taken in a suicide attempt (eg, overdose) may be eligible for study participation per clinician judgment and in consultation with the sponsor’s medical monitor.
    9. Subject has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered to have minimal risk of recurrence).
    10. Subject has any anatomical or medical condition that, per the investigator’s clinical judgment based on assessment, may impede delivery or absorption of intranasal study drug.
    11. Subject has known allergies, hypersensitivity, intolerance or contraindications to esketamine or ketamine or its excipients (refer to Investigator's Brochure for esketamine, Summary of Product Characteristics, US prescribing information).
    12. Subject has taken any disallowed therapy(ies) as noted in Section 8, Prestudy and Concomitant Therapy, and Attachment 1 of the protocol.
    13. Subject has received an investigational drug (including esketamine, ketamine, or investigational vaccines) or used an invasive investigational medical device within 60 days before the planned first dose of study drug or is currently enrolled in an investigational study.
    14. Subject is a woman who is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 3 months after the last dose of study drug.
    15. Subject has any situation or condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments.
    16. Subject is an employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.
    1.El sujeto tiene un diagnóstico actual, según los criterios del DSM-5, de trastorno bipolar, antisocial de la personalidad, u obsesivo compulsivo.
    2.El sujeto cumple actualmente los criterios del DMS-5 para trastorno límite de la personalidad.
    -También se excluirá a los sujetos que no cumplan todos los criterios del DSM-5 para trastorno límite de la personalidad, pero muestren rasgos o amenazas suicidas recurrentes o conductas de automutilación.
    3.El sujeto tiene un diagnóstico actual de autismo, demencia o discapacidad intelectual.
    4.El sujeto tiene un diagnóstico actual o previo, según los criterios del DSM-5, de trastorno psicótico o de TDM con rasgos psicóticos.
    5.El sujeto tiene antecedentes de trastorno moderado o grave de abuso de sustancias psicoactivas o alcohol según los criterios del DSM-5, excepto nicotina o cafeína, en los 6 meses previos a la selección.
    6. Criterio modificado por la Enmienda 1:
    6.1 El sujeto tiene una de las siguientes condiciones:
    - antecedentes o signos y síntomas actuales de insuficiencia hepática o renal. - enfermedad cardíaca (incluida la cardiopatía coronaria inestable, insuficiencia cardiaca congestiva, taquiarritmias, e infarto de miocardio reciente) vascular, pulmonar, gastrointestinal, endocrina (incluido el hipertiroidismo incontrolado), hematológica, reumatológica o metabólica (incluida la deshidratación/hipovolemia severas) clínicamente significativa.
    7. Criterio modificado por la enmienda 1
    7.1 El sujeto tiene hipertensión no controlada (presión arterial sistólica>140 mm Hg o presión arterial diastólica>90 mm Hg) a pesar de la dieta, el ejercicio y dosis estables de medicación antihipertensiva durante al menos dos semanas antes de la selección. -Sujetos cuya elevación de la presión arterial pueda suponer un grave riesgo (incluidas la angina inestable, enfermedad cardiovascular severa, daño cerebral reciente, aumento de la presión intracraneal/ masa intracraneal, sangrado intracraneal o ictus agudo, glaucoma sin tratar o lesión perforante del ojo) están excluidas. – Un valor de presión arterial anormal en la selección puede repetirse una vez, después de5 min de relajación, para determinar su elegibilidad. En el día 1 de la fase de tratamiento antes de la randomización, una presión arterial sistólica en posición supina o semi supina >140 mmHg o diastólica >90mmHg es excluyente.
    8. El sujeto da positivo en el test de orina para fenciclidina, cocaína o anfetaminas en la selección. _Los sujetos que den positivo al test por un uso apropiado de opiáceos, benzodiacepinas o barbitúricos prescritos podrán ser elegido para participación en estudio a juicio clínico. Además, los sujetos que den positivo a estas sustancias sin prescripción, o por ser tomadas en el intento de suicidio (ej. Sobredosis) pueden ser considerados elegibles por juicio clínico tras consulta con el médico especialista del sponsor.
    9. El sujeto tiene un historial de cáncer en los 5 años previos a la selección (excepto cáncer de piel de las células basales y escamosas, y carcinoma de cérvix in situ u otro cáncer que, en opinión del investigador, con coincidencia del médico especialista del sponsor, se considere que tenga un riesgo mínimo de recurrencia.
    10.El sujeto padezca un trastorno anatómico o médico que, en opinión clínica del investigador basada en la evaluación, puede impedir la libración o absorción del fármaco intranasal del estudio.
    11.El sujeto tiene alergia, hipersensibilidad, intolerancia o contraindicación conocida a las esketamina o ketamina o sus excipientes (ref, IB para esketamina, resumen de las características del producto, prospecto).
    12.El sujeto ha recibido algún tratamiento/s prohibido como se señala en la secc.8, tratamiento previo al estudio y concomitante, y Anexo 1.
    13.El sujeto ha recibido un medicamento en investigación (incluidas esketamna, ketamina o vacunas en investigación) o a
    usado un dispositivo médico invasivo en investigación en los 60días anteriores a la primera dosis planeada del medicamento en investigación, o está actualmente incluido en un ensayo clínico.
    14. El sujeto es una mujer que está embarazada o amamantando, o que planea quedarse embarazada mientras participe en el ensayo o en los siguientes 3 meses a la última dosis del fármaco de estudio.
    15. El sujeto tiene una situación o condición por la cual, en opinión del investigador, la participación en el estudio no sería la mejor para él (p.ej. afectaría a su bienestar) o podría impedir, limitar o constituir un factor de confusión en las evaluaciones especificadas en el protocolo.
    16.El sujeto es un empleado del investigador o del centro del estudio con participación directa en el estudio propuesto o en otros ensayos bajo la dirección de ese investigador o centro de estudio, lo que incluye también a los familiares de los empleados o del investigador.
    E.5 End points
    E.5.1Primary end point(s)
    Change from baseline in depressive symptoms, as measured by the Montgomery-Asberg Depression Rating Scale (MADRS) total score
    Variación de los síntomas depresivos dessde el momento basal, determinada por la
    puntuación total en la escala MADRS
    E.5.1.1Timepoint(s) of evaluation of this end point
    Day 1, predose to 24 hours post first dose
    Día 1, predosis hasta 24 horas después de la primera dosis
    E.5.2Secondary end point(s)
    1) Change from baseline in severity of suicidality, as measured by the clinical global impression of severity of suicidality revised version (CGI-SS-R)
    2) Remission rate (MADRS ≤12)
    3) Change from baseline of MADRS total score
    4) Change from baseline of CGI-SS-R
    5) Proportion of subjects achieving resolution of suicidality (CGI-SS-R score of 0 or 1)
    6) Change from baseline of clinical global impression of imminent suicide risk (CGI SR-I)
    7) Change from baseline of Beck Hopelessness Scale (BHS)
    8) Change from baseline of European Quality of Life (EuroQol) Group, 5-Dimension, 5-Level (EQ-5D-5L)
    9) Change from baseline of Quality of Life in Depression Scale (QLDS)
    10) Treatment Satisfaction Questionnaire for Medication (TSQM-9) scores
    11) Suicidal Ideation and Behaviors Assessment Tool (SIBAT): Change from baseline in Module 3 My Current Thinking and Module 5 My Risk, Question 3 (patient-reported frequency of suicidal thinking)
    12) Pharmacokinetics: Plasma esketamine and noresketamine concentrations will be summarized; plasma concentrations of esketamine (and noresketamine concentrations, if warranted) will be included in a population analysis
    13) Safety endpoints will be evaluated throughout the study - Monitoring of treatment emergent adverse events (TEAEs), Clinical laboratory tests, physical examination, nasal examination, 12-lead electrocardiogram (ECG), and vital signs, SIBAT, On dosing days only: MOAA/S, CADSS, and pulse oximetry
    1) Variación de la intensidad del riesgo de suicidio, determinado por CGI-SS-R
    2) Tasa de remisión (MADRS # 12)
    3) Variación de la puntuación total en la MADRS desde el momento basal.
    4) Variación desde el momento basal de la CGI-SS-R
    5) Proporción de sujetos que logran una resolución del riesgo de suicidio (puntuación de 0 a 1 en la CGI-SS-R)
    6) Variación desde el momento basal de la CGI SR-I
    7) Variación desde el momento basal de la Beck Hopelessness Scale (BHS)
    8) Variación desde el momento basal del European Quality of Life (EuroQol) Group, 5-Dimension, 5-Level (EQ-5D-5L)
    9) Variación desde el memento basal del Quality of Life in Depression Scale (QLDS)
    10) Puntuaciones del Treatment Satisfaction Questionnaire for Medication (TSQM-9)
    11) Suicidal Ideation and Behaviors Assessment Tool (SIBAT): Variación en el Módulo 3 Mi Pensamiento Actual y
    Módulo 5 Mi Riesgo, Pregunta 3 (frecuencia de pensamientos suicidas comunicada por el paciente)
    12) Farmacocinética: Se resumirán las concentraciones plasmáticas de esketamina y noresketamina; las concentraciones plasmáticas de esketamina (y noresketamina, si está justificado) se incluirán en un análisis poblacional
    13) Los criterios de valoración de la seguridad se evaluarán durante todo el estudio - Vigilancia de acontecimientos adversos aparecidos con el tratamiento (AAAT), Análisis clínicos, exploración física, exploración nasal, electrocardiograma (ECG) de 12 derivaciones y constantes vitales, SIBAT, los días de administración: MOAA/S, CADSS y pulsioximetría
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) From day 1, predose to 24 hours post first dose
    2, 5, 6) 4 hours and 24 hours post first dose, and through the end of the double-blind treatment phase (Day 25)
    3,4) 4 hours post first dose and through the end of the double-blind treatment phase (Day 25)
    7, 8, 9, 10, 11) Through the end of the double-blind treatment phase (Day 25)
    12, 13) Throughout the study
    1) Desde el día 1, predosis hasta 24 horas después de la primera dosis
    2, 5, 6) 4 horas y 24 horas después de la primera dosis y hasta el final de la fase del
    tratamiento doble ciego (Día 25) 3,4) 4 horas después de la primera dosis y hasta el
    final de la fase del tratamiento doble ciego (Día 25)
    7,8,9,10,11) Hasta el final de la fase del tratamiento doble ciego (Día 25)
    12,13) Durante el 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 Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    E.6.12Pharmacoeconomic Yes
    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) No
    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 concerned11
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA21
    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
    Bulgaria
    Estonia
    Germany
    Hungary
    Korea, Republic of
    Malaysia
    Slovakia
    South Africa
    Spain
    Taiwan
    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 months4
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months4
    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: 224
    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 state32
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 87
    F.4.2.2In the whole clinical trial 224
    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)
    Not applicable
    No aplica
    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 Decision2017-05-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2017-03-31
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2018-12-18
    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA