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    Summary
    EudraCT Number:2014-004588-19
    Sponsor's Protocol Code Number:ESKETINTRD3005
    National Competent Authority:Bulgarian Drug Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2016-11-03
    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 ConcernedBulgarian Drug Agency
    A.2EudraCT number2014-004588-19
    A.3Full title of the trial
    A Randomized, Double-blind, Multicenter, Active-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Subjects with Treatment-resistant Depression

    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants with Treatment-resistant Depression
    A.3.2Name or abbreviated title of the trial where available
    (TRANSFORM-3)
    A.4.1Sponsor's protocol code numberESKETINTRD3005
    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 International NV
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressJanssen Biologics BV - Clinical Registry Group-Archimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333CM
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+3171524 21 66
    B.5.5Fax number+3171524 21 10
    B.5.6E-mailClinicalTrialsEU@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 hydrochloride (for (S)-2-(o-chlorophenyl)-2-(methylamino)cyclohexanone hydrochloride)
    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.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
    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 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 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.IMP: 6
    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 37.5 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 number37.5
    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: 7
    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 number25
    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
    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.
    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 19.0
    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 evaluate the efficacy of switching elderly subjects with TRD from a prior antidepressant treatment (to which they have not responded) to flexibly dosed intranasal esketamine (28 mg, 56 mg or 84 mg) plus a newly initiated oral antidepressant compared with switching to a newly initiated oral antidepressant (active comparator) plus intranasal placebo, in improving depressive symptoms, as assessed by the change from baseline in the Montgomery-Asberg Depression Rating Scale (MADRS) total score from Day 1 (pre-randomization) to the end of the 4-week double-blind induction phase.
    E.2.2Secondary objectives of the trial
    To assess the effect of intranasal esketamine plus a newly initiated oral antidepressant compared with a newly initiated oral antidepressant (active comparator) plus intranasal placebo on the following parameters in elderly subjects with TRD:
    -Depression response rates,
    -Depression remission rates,
    -Overall severity of depressive illness,
    -Health-related quality of life and health status.

    To investigate the safety and tolerability of intranasal esketamine plus a newly initiated oral antidepressant compared with a newly initiated oral antidepressant (active comparator) plus intranasal placebo in elderly subjects with TRD. For list of parameters see protocol page 68.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    -At the time of signing the informed consent form (ICF), parti cipant must be a man or woman 65 years of age or older
    -At the start of the Screening/prospective observational Phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM5)
    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 MiniInternational Neuropsychiatric Interview (MINI)
    -At the start of the Screening/Prospective observational Phase, participant must have an Inventory of Depressive Symptomatology Clinician rated (IDSC30)
    total score of greater than or equal to (>=) 31
    -At the start of the Screening/Prospective observational Phase, participants must have had nonresponse (less than or equal to 25% improvement) to >=1 but less than or equal to (<=) 8 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital – Antidepressant Treatment Response Questionnaire (MGHATRQ) and documented records by medical and pharmacy/prescription records, or a letter from the treating physician, etc,). In addition, subject is taking a different oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose.
    -Participant must be taking one of the oral antidepressant treatment with nonresponse that is documented on the MGHATRQ at the start of the screening/prospective observational phase
    -The participant’s current major depressive episode, depression symptom severity (Week 1 MADRS total score greater than or equal to 24 required) and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be confirmed for participation in a clinical study based on a Site Independent Qualification Assessment
    -Participant must be medically stable on the basis of clinical laboratory tests
    performed in the screening/prospective observational phase
    E.4Principal exclusion criteria
    -The participant's depressive symptoms have previously demonstrated nonresponse to: Esketamine or ketamine in the current major depressive episode per clinical judgment, or all of the 4 oral antidepressant treatment options available for the doubleblind induction Phase (Duloxetine, Escitalopram, Sertraline, and Venlafaxine extended release [XR]) in the current major depressive episode (based on MGHATRQ), 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
    -Participants who has received vagal nerve stimulation (VNS) or who has received deep brain stimulation (DBS) in the current episode of depression
    -Participant has a current or prior DSM5 diagnosis of a psychotic disorder or MDD with psychosis, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current episode only), intellectual disability ( intellectual disability [DSM5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 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 (CSSRS)
    and also includes history of suicidal behavior within the past year prior to start of the screening/prospective observational phase
    -Participant has a history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4 methylenedioxymethamphetamine (MDMA) hallucinogen related use disorder
    -Participant has a Mini Mental State Examination (MMSE) less than (<) 22
    -Subject has neurodegenerative disorder (eg, Alzheimer’s Disease, Vascular dementia, Parkinson’s disease with clinical evidence of cognitive impairment) or evidence of mild cognitive impairment (MCI).
    -Participant has a history of uncontrolled hypertension; current or past history of significant pulmonary insufficiency/condition;clinically significant ECG abnormalities; current or past history of seizures; clinically significant cardiovascular disorders including cerebral and cardiac vascular disease
    E.5 End points
    E.5.1Primary end point(s)
    Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at end of Double-Blind Induction Phase
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and End of Double-blind Induction Phase (Week 4)
    E.5.2Secondary end point(s)
    1) Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire – 9 (PHQ-9) Total Score at end of Double-Blind Induction Phase
    2) Change From Baseline in Subject-reported Functioning and Associated Disability as Assessed by the Sheehan Disability Scale (SDS) Total Score at end of Double-Blind Induction Phase
    3) Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at end of Double-Blind Induction Phase
    4) 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 Double-Blind Induction Phase
    5) Number of Participants with Adverse Events (AEs) and Serious AEs
    E.5.2.1Timepoint(s) of evaluation of this end point
    1) Baseline and End of Double-blind Induction Phase (Week 4)
    2) Baseline, Day 15 and End of Double-blind Induction Phase (Week 4)
    3) Baseline and End of Double-blind Induction Phase (Week 4)
    4) Baseline and End of Double-blind Induction Phase (Week 4)
    5) Screening up to end of Follow-up Phase (approximately up to 13 Weeks)
    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 Yes
    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 concerned5
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA32
    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
    Bulgaria
    France
    Italy
    Poland
    South Africa
    Spain
    Sweden
    United Kingdom
    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
    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 months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years2
    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) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 148
    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 No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    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 state18
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 94
    F.4.2.2In the whole clinical trial 148
    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)
    At the end of the DB induction phase, regardless of response status, subjects may be eligible to participate in study ESKETINTRD3004 (long-term open-label safety study) if they meet all other study entry criteria. For those subjects who withdraw early or choose not to participate in study ESKETINTRD3004, following a 2-week follow up phase, further clinical/standard of care for the treatment of depression will be arranged by the study investigator and/or the subject’s treating physician.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-12-08
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-11-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2017-08-08
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