A Long-term Comparison of Esketamine Nasal Spray Versus Quetiapine Extended Release, Both in Combination With a Selective Serotonin Reuptake Inhibitor/Serotonin-Norepinephrine Reuptake Inhibitor, in Participants With Treatment Resistant Major Depressive Disorder (ESCAPE-TRD)
Depressive Disorder, Major
About this trial
This is an interventional treatment trial for Depressive Disorder, Major
Eligibility Criteria
Inclusion Criteria:
- At screening, each participant must meet Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent MDD, without psychotic features, based on clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI)
- At screening and baseline, each participant must have an Inventory of Depressive Symptomatology - Clinician-rated, 30 item (IDS-C30) total score of greater than or equal to (>=) 34
- Must be on a current antidepressive treatment that includes an selective serotonin reuptake inhibitor (SSRI)/ serotonin-norepinephrine reuptake inhibitor (SNRI) at screening that resulted in nonresponse (less than 25% improvement of symptoms) after having been given at an adequate dosage (based on antidepressive dosages from SmPC [or local equivalent, if applicable]) for an adequate duration of at least 6 weeks and having been uptitrated to the maximum tolerated dose; however, at screening the participant must show signs of minimal clinical improvement to be eligible for the study. Clinical improvement of a participant on their current AD treatment will be retrospectively evaluated in a qualified psychiatric interview performed by an experienced clinician. At baseline (Day 1) prior to randomization, the investigator will evaluate any changes in the participant's signs/symptoms of depression since the screening assessment and confirm that the inclusion criteria for the current AD treatment are still met (that is nonresponse and minimal clinical improvement)
- The current antidepressive treatment, was immediately preceded by nonresponse to at least 1 but not more than 5 different, consecutive treatments (all within the current moderate to severe antidepressive episode) with anti-depressants (ADs) taken at an adequate dosage for an adequate duration of at least 6 weeks and must be documented
- Must have been treated with at least 2 different antidepressive substance classes among the treatments taken at an adequate dosage for an adequate duration of at least 6 weeks resulting in nonresponse in the current moderate to severe depressive episode (including the current treatment with an selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor [SSRI/SNRI])
- Must be on a single oral SSRI/SNRI on Day 1 prior to randomization
Exclusion Criteria:
- Received treatment with esketamine or ketamine in the current moderate to severe depressive episode
- Received treatment with quetiapine extended- or immediate-release in the current moderate to severe depressive episode of a dose higher than 50 milligram per day (mg/day)
- Had depressive symptoms in the current moderate to severe depressive episode that previously did not respond to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT
- Has no signs of clinical improvement at all or with a significant improvement on their current AD treatment that includes an SSRI/SNRI as determined at screening by an experienced clinician during the qualified psychiatric interview
- Received vagal nerve stimulation or has received deep brain stimulation in the current episode of depression
- has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the Mini International Neuropsychiatric Interview [MINI]), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, or antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
- age at onset of first episode of MDD was more than or equal to (>=) 55 years
- has homicidal ideation or intent, per the investigator's clinical judgment; or has suicidal ideation with some intent to act within 1 month prior to screening, per the investigator's clinical judgment; or based on the Columbia-Suicide Severity Rating Scale (C-SSRS), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation, or a history of suicidal behavior within the past year prior to screening. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the acute phase should also be excluded
Sites / Locations
- FunDaMos
- Fundacion para el Estudio y Tratamiento de las Enfermedades Mentales
- CEN-Consultorios Especializados en Neurociencias
- Fundacion Lennox
- Instituto Médico DAMIC
- Sanatorio Prof. Leon S. Morra S.A
- Instituto de Neurociencias San Agustín
- C.I.A.P. (Centro de investigación y Asistencia en Psiquiatría)
- Medical University Graz
- Schmitz and Schmitz
- Medical University Vienna, MUV
- Anima
- Pz Duffel
- Clinique Psychiatrique des Frères Alexiens
- Sint-Franciskusziekenhuis
- ARIADNE
- CHU de Liège
- CPN - Centro de Pesquisa em Neurociências Ltda
- Trial Tech Tecnologia em Pesquisas com Medicamentos
- Ruschel Medicina e Pesquisa Clínica Ltda
- C.J.S. Carvalho & Carvalho LTDA (Viver - Centro De Desospitalizacao Humana)
- BR Trials
- State Psychiatric Hospital Kardzhali
- UMHAT 'Dr. Georgi Stranski', EAD
- Mental Health Center - Plovdiv
- Mental Health Center - Rousse
- Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
- MHC - Sofia, EOOD
- Centre for Mental Health Prof.N.Shipkovenski EOOD
- University Multiprofile Hospital for Active Treatment - UMHAT Alexandrovska EAD
- Psychiatricka ambulance Saint Anne s.r.o.
- Psychiatricka ambulance, MUDr. Marta Holanova
- NeuropsychiatrieHK, s.r.o.
- A-Shine s.r.o.
- Institut Neuropsychiatricke pece
- Clintrial s.r.o.
- AD71 s.r.o.
- Medical Services Prague s.r.o.
- Aalborg University Hospital
- Psykiatrien i Region Syddanmark
- Mederon LTD at ARTES
- Psykiatrinen Palvelukeskus Solvum Oy
- Savon Psykiatripalvelu
- Universitaetsklinikum der RWTH Aachen
- Rheinhessen Fachklinik Alzey
- Emovis GmbH
- Charite Campus Benjamin Franklin
- Medizinisches Versorgungszentrum LiO GmbH
- Alexander Schulze - Germany
- Praxis Dr. med. Kirsten Hahn
- Vivantes Klinikum Spandau
- Universitatsklinikum Bonn
- Klinikum Chemnitz gGmbH
- Carl-Thiem-Klinikum Cottbus gGmbH
- Klinikum Dortmund gGmbH
- Universitatsklinikum Carl Gustav Carcus Dresden
- Universitatsklinikum Frankfurt
- Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik
- SRH Waldklinikum Gera GmbH
- Georg-August Universität, Universitätsmedizin Göttingen
- Evangelisches Krankenhaus Bethanien gGmbH
- Universitaetsklinik Hamburg-Eppendorf
- Klinische Forschung Hamburg
- Klinische Forschung Hannover-Mitte GmbH
- Medizinische Hochschule Hannover
- Universität Heidelberg
- Oberhavel Kliniken GmbH
- Universitätsklinikum des Saarlandes
- Universitätsklinikum Jena
- Panakeia - Arzneimittelforschung GmbH
- Universitaetsklinikum Magdeburg A.oe.R
- Universitätsmedizin der Johannes Gutenberg-Universität Mainz
- Pharmakologisches Studienzentrum Chemnitz GmbH
- Universitätsklinikum Münster
- Ruppiner Kliniken
- Praxis Prof. Steinwachs
- Johanniter Krankenhaus Oberhausen
- Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik
- Somni Bene GmbH
- Klinische Forschung Schwerin GmbH
- Klinikum der Hansestadt Stralsund GmbH-Ambulanz-Klinik für Psychiatrie und Psychotherapie - Germany
- Aiginition Hospital of Athens
- 'Dafni' Psychiatric Hospital of Attica
- Venizeleio General Hospital
- Psychiatric Clinic 'Agios Charalampos'
- University General Hospital of Ioannina
- University General Hospital of Rio Patras
- 424 Military Hospital of Thessaloniki
- Psychiatric Hospital of Thessaloniki
- 'G. Papanikolaou' Hospital of Thessaloniki
- Semmelweis Egyetem
- Észak-Közép-budai Centrum, Új Szent János Kórház és Szakrendelő Budai Családközpontú
- Processus Kft.
- Debreceni Egyetem, Kenézy Gyula Egyetemi Oktatókórház
- Bugat Pal Korhaz
- Petz Aladar Megyei Oktato Korhaz
- Bács-Kiskun Megyei Kórház a Szegedi Tudományegyetem Általános Orvostudományi Kar Oktató Kórháza
- Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz
- Pecsi Tudomanyegyetem Klinikai Kozpont
- Rambam Medical Center
- Shalvata Mental Health Center
- Beer Yaakov Mental Health Center
- Geha Mental Health Center
- Sheba Medical Center
- Tel Aviv Sourasky Medical Center
- Republican Scientific and Practical Center of Mental Health
- Medical Center for Psychological Healt SME
- East-Kazakhstan Regional Centre of Mental Health
- Chonnam National University Hospital
- Wonkwang University Hospital
- KyungHee University Hospital
- Korea University Anam Hospital
- Severance Hospital, Yonsei University Health System
- Samsung Medical Center
- Hospital Raja Permaisuri Bainun
- Hospital Kuala Lumpur
- University Malaya Medical Centre
- Hospital Pengajar Universiti Putra Malaysia
- Hospital Tuanku Jaafar
- Brain Research Center
- AMC
- LUMC
- Haukeland University Hospital
- Sykehuset Ostfold
- St Olav University Hospital
- Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
- Osrodek Badan Klinicznych CLINSANTE S.C.
- Uniwersyteckie Centrum Kliniczne
- Centrum Badań Klinicznych PI-House sp. z o.o.
- Centrum Medyczne Care Clinic Katowice
- Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
- Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego
- SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
- Centrum Medyczne Luxmed Sp z o o
- Osrodek Badan Klinicznych CLINSANTE S.C.
- Hospital de Braga
- Centro Hospitalar do Tâmega e Sousa, EPE - Hospital Padre Americo, Vale do Sousa
- Fundação Champalimaud
- Centro Hospitalar de Lisboa Norte - Hospital Santa Maria
- Hospital CUF Tejo
- Hospital Beatriz Angelo
- Cape Town Clinical Research Centre
- Flexivest 14 Research
- Gert Bosch - Pretoria South Africa
- Psykiatriska kliniken
- Affecta Pskyiatrimottagning
- Psykiatriska kliniken
- ProbarE i Lund AB
- ONE LIFETIME Läkarmottagning
- ProbarE i Stockholm AB
- Changhua Christian Hospital
- Hualien Tzu Chi Hospital
- Kai-Syuan Psychiatric Hospital
- Chang Gung Memorial Hospital
- National Cheng Kung University Hospital
- Taipei Medical University
- National Taiwan University Hospital
- Mackay Memorial Hospital
- Taipei Veterans General Hospital
- Chang Gung Memorial Hospital
- Hacettepe University Medical Faculty
- Bursa Yuksek Ihtisas Training and Research Hospital
- Uludag University Medical Faculty
- Bakirkoy Mental Health Training and Research Hospital
- Erenkoy Mental Health Hospital
- Uskudar University Neuropsychiatry Hospital
- Ege Universitesi Tip Fakultesi
- Selcuk University Medical Faculty
- Liv Hospital
- Namik Kemal University
- American Center for Psychiatry and Neurology
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Esketamine Arm
Comparator Arm
Participants will receive treatment with esketamine nasal spray (28 milligram [mg] [initial dose for elderly participants 65 to 74 years of age and adults of Japanese ancestry; may be used throughout the study in these populations; may be uptitrated in 28 mg increments], 56 mg [initial dose for adult participants aged 18 to 64 years and may be used for all age groups throughout the study], or 84 mg [maximum dose esketamine nasal spray may be uptitrated to]) twice-weekly with a flexible dose regimen from Day 1 until Week 4, once weekly from Week 5 to Week 8 and once-weekly or once every 2 weeks from Week 9 to Week 32 in combination with continuing serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI).
Participants will continue to take their current SSRI/SNRI augmented with quetiapine extended release (XR) as per the Summary of Product Characteristics (SmPC) (or local equivalent, if applicable). In adult participants aged 18 to 64 years, the initial dose is 50 mg/day on Days 1-2, 150 mg/day on Days 3-4 [lowest effective dose]; a further dose increase to 300 mg/day on Day 5 and onward will be based on individual participant evaluation. In elderly participants aged 65 to 74 years, the initial dose is 50 mg/day on Days 1-3, 100 mg/day on Days 4-7, and 150 mg/day on Day 8; a further dose increase to 300 mg/day will be based on individual participant evaluation no earlier than Day 22.