Depressive Disorder, MajorPhase 4ESCAPE-LTENCT04829318
A Long-Term Extension Study for Participants With Treatment-resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment
A Phase 4 study testing Esketamine and SSRI/SNRI in people with Depressive Disorder, Major, run by Janssen-Cilag Ltd. at 59 sites in 14 countries.
Trial summary
The primary purpose of this study is to assess the long-term safety and tolerability of esketamine nasal spray in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in participants who have completed 32 weeks of esketamine nasal spray treatment in Study… Read more about this study
- Who is it for?
- Ages 18 to 74 years
- Conditions the study is for
- Depressive Disorder, Major
- What is being tested?
- Esketamine and SSRI/SNRI
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 183 participants
- Where
- 59 sitesin 14 countries
- Study dates
- 26 Apr 2021to 22 Jul 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Completed the maintenance phase (Week 32) of Study 54135419TRD3013 (NCT04338321) and had esketamine nasal spray in combination with continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) administered through Week 30 (every 2 week dosing) or Week 31 (once weekly dosing) of Study 54135419TRD3013, and continues to be willing to be treated with esketamine nasal spray
- Must, in the opinion of the investigator, be benefiting from continuation of esketamine nasal spray in combination with their current SSRI/SNRI based on efficacy and tolerability assessed on Day 1 of this study
- Must be medically stable based on the investigator's judgment
- A woman of childbearing potential must have a negative urine pregnancy test on Day 1
- Male participants who are sexually active with a woman of childbearing potential must agree to the following during the intervention period and for at least 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study intervention (that is, esketamine nasal spray), must fulfill the following criteria: must be practicing a highly effective method of contraception with his female partner, must use a condom if his partner is pregnant, and must agree not to donate sperm
Who cannot join
- Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
- Completed Study 54135419TRD3013 while presenting adverse events deemed clinically relevant by the investigator, and which may interfere with safety and well-being of the participant
- Has developed during participation in Study 54135419TRD3013 any of the following cardiovascular-related conditions where an increase in blood pressure or intracranial pressure poses a serious risk: cerebrovascular disease following stroke or transient ischemic attack, aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels), intracerebral hemorrhage, coronary artery disease following myocardial infarction, unstable angina, or revascularization procedure (example, coronary angioplasty or bypass graft surgery), uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability, hemodynamically significant valvular heart disease such as mitral regurgitation, aortic stenosis, or aortic regurgitation or heart failure (New York Heart Association [NYHA] Class III-IV) of any etiology
- Significant pulmonary insufficiency, including chronic obstructive pulmonary disease
- 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 Day 1, per the investigator's clinical judgment; or based on the Columbia-suicide severity rating scale (C-SSRS) performed at Week 32 visit of Study 54135419TRD3013, 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
- Pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within 90 days after the last dose of study intervention
Trial locations and contacts
59 sites in 14 countries.
59 sites in 14 countries
Germany10 sites
Medizinisches Versorgungszentrum LiO GmbH
Berlin, 12209
Praxis Dr. med. Kirsten Hahn
Berlin, 13187
Klinikum Dortmund gGmbH
Dortmund, 44287
Universitätsklinikum Freiburg - Abteilung für Psychiatrie u. Psychotherapie mit Poliklinik
Freiburg im Breisgau, 79104
Klinische Forschung Hamburg
Hamburg, 20253
Oberhavel Kliniken GmbH
Hennigsdorf, 16761
Pharmakologisches Studienzentrum Chemnitz GmbH
Mittweida, 09111
Danuvius Klinik Pfaffenhofen Fachklinik für Psychiatrie, Psychotherapie und Psychosomatik
Pfaffenhofen, 85276
Somni Bene GmbH
Schwerin, 19053
Klinische Forschung Schwerin GmbH
Schwerin, 19055
Poland9 sites
Mlynowamed Specjalistyczny Psychiatryczny Gabinet Lekarski Joanna Lazarczyk
Bialystok, 15-404
Osrodek Badan Klinicznych CLINSANTE S C
Bydgoszcz, 85 794
Uniwersyteckie Centrum Kliniczne
Gdansk, 80 214
Centrum Badan Klinicznych PI House sp z o o
Gdansk, 80 546
Centrum Medyczne Care Clinic Katowice
Katowice, 40-568
Niepubliczny Zaklad Opieki Psychiatrycznej MENTIS
Leszno, 64-100
Specjalistyczny Psychiatryczny Zespol Opieki Zdrowotnej w Lodzi Szpital im. J. Babinskiego
Lodz, 91-229
SPZOZ CSK UM w Lodzi Klinika Zaburzen Afektywnych i Psychotycznych
Lodz, 92-216
Osrodek Badan Klinicznych CLINSANTE S C
Torun, 87 100
Argentina7 sites
FunDaMos
Buenos Aires, C1405BOA
CEN Consultorios Especializados en Neurociencias
Córdoba, 5000FJF
Fundacion Lennox
Córdoba, 5000
Instituto Medico DAMIC
Córdoba, X5003DCE
Sanatorio Prof Leon S Morra S A
Córdoba, X5009BIN
Instituto de Neurociencias San Agustin
La Plata, 1900
C I A P Centro de investigacion y Asistencia en Psiquiatria
Rosario, 2000
Czechia7 sites
Psychiatricka ambulance Saint Anne s.r.o.
Brno, 60200
Psychiatricka ambulance, MUDr. Marta Holanova
Brno, 61500
NeuropsychiatrieHK, s.r.o.
Hradec Králové, 50002
A Shine S R O
Pilsen, 31200
AD71 s.r.o.
Prague, 109 00
Medical Services Prague S R O
Prague, 16000
Institut Neuropsychiatricke pece
Prague, 18600
Malaysia4 sites
Hospital Raja Permaisuri Bainun
Ipoh, 30990
University Malaya Medical Centre
Kuala Lumpur, 59100
Hospital Pengajar Universiti Putra Malaysia
Serdang, 43400
Hospital Tuanku Jaafar
Seremban, 70300
Taiwan4 sites
Changhua Christian Hospital
Changhua, 500
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Chang Gung Memorial Hospital
Taoyuan, 333
Bulgaria3 sites
Mental Health Center - Rousse
Rousse, 7003
Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum
Sofia, 1113
Centre for Mental Health Prof.N.Shipkovenski EOOD
Sofia, 1377
Greece3 sites
Psychiatric Clinic 'Agios Charalampos'
Heraklion, 71305
University General Hospital of Rio Patras
Pátrai, 26504
G Papanikolaou Hospital of Thessaloniki
Thessaloniki, 57010
Hungary3 sites
Processus Kft
Budapest, 1137
Bugat Pal Korhaz
Gyöngyös, 3200
Petz Aladar Megyei Oktato Korhaz
Győr, H-9024
Turkey (Türkiye)3 sites
Hacettepe University Medical Faculty
Ankara, 6100
Erenkoy Mental Health Hospital
Istanbul, 34736
Liv Hospital
Samsun, 55020
South Africa2 sites
Cape Town Clinical Research Centre
Cape Town, 7530
Gert Bosch Pretoria South Africa
Pretoria, 0 042
South Korea2 sites
Severance Hospital Yonsei University Health System
Seoul, 03722
Samsung Medical Center
Seoul, 06351
About this study
Official title: Open-label Long-Term Extension Study for Participants With Treatment-Resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment From Study 54135419TRD3013
The primary purpose of this study is to assess the long-term safety and tolerability of esketamine nasal spray in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in participants who have completed 32 weeks of esketamine nasal spray treatment in Study 54135419TRD3013 (NCT04338321).
- Conditions
- Depressive Disorder, Major
- Being tested
- Esketamine, SSRI/SNRI
- Keywords
- Treatment resistant depression
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EsketamineDrug
Esketamine will be self-administered as nasal spray.
SSRI/SNRIDrug
Participants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the summary of product characteristics (SmPC) (or local equivalent, if applicable). During this LTE study, investigators will be allowed to switch individual participant's SSRI/SNRI for tolerability issues.
| Study group | Role | What they receive |
|---|---|---|
| Esketamine | Experimental | Participants who were randomly assigned to the esketamine arm in Study 54135419TRD3013 (NCT04338321), had esketamine nasal spray administered through Week 30 (every 2 weeks dosing) or Week 31 (once weekly dosing), completed the maintenance phase at Week 32 will continue to receive esketamine nasal spray once weekly or every 2 weeks along with serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. The duration of the study participation is 2 years or when esketamine is commercially available. Receives: Drug: Esketamine; Drug: SSRI/SNRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Percentage of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence Rate of Treatment-emergent Adverse Events (TEAEs)
Incidence rate of TEAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Percentage of participants with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence Rate of Treatment-emergent Serious Adverse Events (TESAEs)
Incidence rate of with TESAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of of Participants With TEAEs Leading to Death
Percentage of participants with TEAEs leading to death were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence Rate of TEAEs Leading to Death
Incidence rate of TEAEs leading to death were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of Participants With Treatment-emergent AEs of Special Interest (AESIs)
Percentage of participants with TEAEs of special interest were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were separately grouped by categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence Rate of Treatment-emergent AEs of Special Interest (AESIs)
AE Incidence rate: incidence rate per 100 patient-months=(number of participants with AE divided by sum of days at risk for AE)* 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. SAE: AE resulting in any following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial intervention administration up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were grouped as categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.
Measured: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Number of Participants With Suicidal Ideation and Behavior in Study 54135419TRD4010 as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score
Number of participants with suicidal ideation and behavior in study 54135419TRD4010 as assessed by C-SSRS score were reported. C-SSRS score: an assessment tool that evaluated suicidal ideation and behavior. Suicidal ideation (5 items): wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, and active suicidal ideation with specific plan and intent. Suicidal behavior (5 items): preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), and suicide. Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior (0), Suicidal ideation (1 to 5), Suicidal behavior (6 to 10). Total score ranged from 0 to 10. Higher scores indicated more severe suicidal ideation and behavior.
Measured: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)
Secondary outcomes (7)
Percentage of Participants With No Relapse and Without Discontinuation Until the End of the Prospective Observation Period at Week 104
Relapse was defined by any of the following: a) Worsening of depressive symptoms as indicated by Montgomery-Asberg Depression Rating Scale (MADRS) total score >=22 confirmed by 1 additional assessment of MADRS total score >=22 within the next 5 to 31 days. b) Any psychiatric hospitalization for: 1) worsening of depression, 2) suicide prevention or due to a suicide attempt for any of these events. c) Suicide attempt, completed suicide, or any other clinically relevant event determined per investigator's clinical judgment to be indicative of relapse of depressive illness, but for which participant was not hospitalized. MADRS scale consisted of 10 items, scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 0 to 60. Higher scores represented a more severe condition.
Measured: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)
Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Change from baseline of study 54135419TRD3013 in Clinician-rated MADRS total score were reported. MADRS was a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items , scored from 0 (item is not present or normal) to 6 (severe or continuous presence of symptoms), summed up for a total possible score range of 0 to 60. Higher scores represented a more severe condition. The MADRS evaluated reported sadness, apparent sadness, inner tension, reduced sleep, reduced appetite, concentration difficulties, lassitude, inability to feel, pessimistic thoughts, and suicidal thoughts.
Measured: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Score Individual Items
Change from Baseline of Study 54135419TRD3013 in Clinician-rated MADRS Score Individual Items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts) were reported. MADRS was a clinician-rated scale designed to measure depression severity and to detect changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed up for a total possible score range of 0 to 60. Higher scores represent a more severe condition.
Measured: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Clinical Global Impression -Severity (CGI-S) Scale Score
Change from Baseline of Study 54135419TRD3013 in CGI-S scale score were reported. The CGI-S provided an overall clinician-determined summary measure of the severity of the participant's illness that took into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluated the severity of psychopathology on a scale of 1 to 7: where, 1 = normal (not ill); 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; 7 = among the most extremely ill participant's. Negative change in score indicated improvement. Participant's with a score of zero were considered missing.
Measured: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Patient Health Questionnaire (PHQ) 9-item Total Score
Change from Baseline of Study 54135419TRD3013 in PHQ 9-item total score were reported. The PHQ-9 was a validated 9-item, patient-reported outcome (PRO) measure to assess depressive symptoms. Each item was rated on a 4-point scale (0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day). The participant's item responses were summed to a total score with a range of 0 to 27. Higher scores indicated greater severity of depressive symptoms.
Measured: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Health Status Index
Change from baseline of Study 54135419TRD3013 in EQ-5D-5LQuestionnaire Score: health status index were reported. The EQ-5D-5L descriptive system comprised the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of the 5 dimensions were divided into 5 levels of perceived problems (level 1 = no problem, level 2 = slight problems, level 3 = moderate problems, level 4 = severe problems, level 5 = extreme problems). The participant selected an answer for each of the 5 dimensions considering a response that best matched participant's health "today." Responses were used to generate health status index ranged from -0.594 to 1 (where 1 represents full health and negative values represent health states considered worse than dead). Positive change in score indicated improvement.
Measured: Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Visual Analogue Scale (VAS)
Change from baseline of Study 54135419TRD3013 in EQ-5D-5L: visual analogue scale were reported. EQ-VAS self-rating recorded the participant's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Positive change in score indicated improvement.
Measured: Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Apr 2021
- Study start26 Apr 2021
- Primary completion22 Jul 2024
- Study completion22 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Depressive Disorder, MajorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 183 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen-Cilag Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen-Cilag Ltd. Clinical Trial, Study director, Janssen-Cilag Ltd.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04829318
- Sponsor's protocol ID
- CR108992
- Other IDs
- 2020-004291-18, 54135419TRD4010
- Acronym
- ESCAPE-LTE
- Status last verified
- Sep 2025
- First submitted
- 1 Apr 2021
- Last updated
- 18 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Long-Term Extension Study for Participants With Treatment-Resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment From Study 54135419TRD3013
- ClinicalTrials.gov ID
- NCT04829318
- Acronym / sponsor ID
- ESCAPE-LTE / CR108992
- Conditions
- Depressive Disorder, Major
- Keywords
- Treatment resistant depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 183 participants (actual)
- Lead sponsor
- Janssen-Cilag Ltd.Industry (pharma, biotech, devices)
- Study start
- 26 Apr 2021 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 2 Apr 2021 (actual)
- Results
- Posted 18 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary purpose of this study is to assess the long-term safety and tolerability of esketamine nasal spray in combination with a selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) in participants who have completed 32 weeks of esketamine nasal spray treatment in Study 54135419TRD3013 (NCT04338321).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Esketamine | Experimental | Drug: Esketamine, Drug: SSRI/SNRIParticipants who were randomly assigned to the esketamine arm in Study 54135419TRD3013 (NCT04338321), had esketamine nasal spray administered through Week 30 (every 2 weeks dosing) or Week 31 (once weekly dosing), completed the maintenance phase at Week 32 will continue to receive esketamine nasal spray once weekly or every 2 weeks along with serotonin-norepinephrine reuptake inhibitor/selective serotonin reuptake inhibitor (SSRI/SNRI) in this long-term extension (LTE) study. The duration of the study participation is 2 years or when esketamine is commercially available. |
Who may qualify
- Ages
- 18 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Completed the maintenance phase (Week 32) of Study 54135419TRD3013 (NCT04338321) and had esketamine nasal spray in combination with continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor (SSRI/SNRI) administered through Week 30 (every 2 week dosing) or Week 31 (once weekly dosing) of Study 54135419TRD3013, and continues to be willing to be treated with esketamine nasal spray
- Must, in the opinion of the investigator, be benefiting from continuation of esketamine nasal spray in combination with their current SSRI/SNRI based on efficacy and tolerability assessed on Day 1 of this study
- Must be medically stable based on the investigator's judgment
- A woman of childbearing potential must have a negative urine pregnancy test on Day 1
- Male participants who are sexually active with a woman of childbearing potential must agree to the following during the intervention period and for at least 1 spermatogenesis cycle (defined as approximately 90 days) after receiving the last dose of study intervention (that is, esketamine nasal spray), must fulfill the following criteria: must be practicing a highly effective method of contraception with his female partner, must use a condom if his partner is pregnant, and must agree not to donate sperm
Key exclusion criteria (6 listed)
- Has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (example, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
- Completed Study 54135419TRD3013 while presenting adverse events deemed clinically relevant by the investigator, and which may interfere with safety and well-being of the participant
- Has developed during participation in Study 54135419TRD3013 any of the following cardiovascular-related conditions where an increase in blood pressure or intracranial pressure poses a serious risk: cerebrovascular disease following stroke or transient ischemic attack, aneurysmal vascular disease (including intracranial, thoracic, or abdominal aorta, or peripheral arterial vessels), intracerebral hemorrhage, coronary artery disease following myocardial infarction, unstable angina, or revascularization procedure (example, coronary angioplasty or bypass graft surgery), uncontrolled brady- or tachyarrhythmias that lead to hemodynamic instability, hemodynamically significant valvular heart disease such as mitral regurgitation, aortic stenosis, or aortic regurgitation or heart failure (New York Heart Association [NYHA] Class III-IV) of any etiology
- Significant pulmonary insufficiency, including chronic obstructive pulmonary disease
- 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 Day 1, per the investigator's clinical judgment; or based on the Columbia-suicide severity rating scale (C-SSRS) performed at Week 32 visit of Study 54135419TRD3013, 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EsketamineEsketamine will be self-administered as nasal spray. | Drug | Esketamine |
| SSRI/SNRIParticipants will continue to take SSRI/SNRI that is approved for use in depression in their country of participation; off-label use of any SSRI/SNRI is not permitted. The continuing SSRI/SNRI dosage may be optimized throughout the study, at the investigator's discretion and based on the summary of product characteristics (SmPC) (or local equivalent, if applicable). During this LTE study, investigators will be allowed to switch individual participant's SSRI/SNRI for tolerability issues. | Drug | Esketamine |
Primary outcome
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Incidence Rate of Treatment-emergent Adverse Events (TEAEs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of TEAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TESAEs were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.
Incidence Rate of Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of with TESAEs were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent.
Percentage of of Participants With TEAEs Leading to Death
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs leading to death were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Incidence Rate of TEAEs Leading to Death
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Incidence rate of TEAEs leading to death were reported. AE Incidence rate was defined as incidence rate per 100 patient-months = (number of participants with AE divided by sum of days at risk for AE) * 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with the intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious adverse events.
Percentage of Participants With Treatment-emergent AEs of Special Interest (AESIs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
Percentage of participants with TEAEs of special interest were reported. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. A SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial administration of study intervention up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were separately grouped by categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.
Incidence Rate of Treatment-emergent AEs of Special Interest (AESIs)
Time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)
AE Incidence rate: incidence rate per 100 patient-months=(number of participants with AE divided by sum of days at risk for AE)* 100*365.25/12. An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non investigational) product. An AE does not necessarily have a causal relationship with intervention. SAE: AE resulting in any following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Any AE occurring at or after the initial intervention administration up to 30 days after last dose in Study 54135419TRD4010 was considered to be treatment emergent. TEAEs included both serious and non-serious AEs. AEs of special interest were grouped as categories sedation, dissociation, suicidality, suggestive of abuse potential, cystitis and hepatic impairment.
Number of Participants With Suicidal Ideation and Behavior in Study 54135419TRD4010 as Assessed by Columbia-suicide Severity Rating Scale (C-SSRS) Score
Time frame: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)
Number of participants with suicidal ideation and behavior in study 54135419TRD4010 as assessed by C-SSRS score were reported. C-SSRS score: an assessment tool that evaluated suicidal ideation and behavior. Suicidal ideation (5 items): wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with any methods (not plan) without intention to act, active suicidal ideation with some intent to act without specific plan, and active suicidal ideation with specific plan and intent. Suicidal behavior (5 items): preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal), and suicide. Total score from 10 categories was summarized into 3 categories: No suicidal ideation or behavior (0), Suicidal ideation (1 to 5), Suicidal behavior (6 to 10). Total score ranged from 0 to 10. Higher scores indicated more severe suicidal ideation and behavior.
7 secondary outcomes
Percentage of Participants With No Relapse and Without Discontinuation Until the End of the Prospective Observation Period at Week 104
Time frame: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)
Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Time frame: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Clinician-rated Montgomery-Asberg Depression Rating Scale (MADRS) Score Individual Items
Time frame: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Clinical Global Impression -Severity (CGI-S) Scale Score
Time frame: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in Patient Health Questionnaire (PHQ) 9-item Total Score
Time frame: Baseline (Day 1 of study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Health Status Index
Time frame: Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Change From Baseline of Study 54135419TRD3013 in European Quality of Life (EuroQol) 5 Dimension 5-Level (EQ-5D-5L): Visual Analogue Scale (VAS)
Time frame: Baseline (Day 1 of Study 54135419TRD3013) up to weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 of study 54135419TRD4010
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janssen-Cilag Ltd. Clinical Trial study director
Janssen-Cilag Ltd.
59 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Esketamine and SSRI/SNRI in people with Depressive Disorder, Major, run by Janssen-Cilag Ltd. at 59 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 59 sites in Germany, Poland, Argentina, Czechia, Malaysia and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) (time frame: From Day 1 of study 54135419TRD4010 up to 30 days after last dose of study drug at Week 104 (up to Week 108)). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.