A Long-Term Extension Study for Participants With Treatment-resistant Major Depressive Disorder Who Are Continuing Esketamine Nasal Spray Treatment

Janssen-Cilag Ltd.183 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

183

Conditions

Depressive Disorder, Major

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 74 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 Exclusion Criteria: * 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

Locations (59)

Outcomes

Primary Outcomes

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.

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 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.

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 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.

Data from ClinicalTrials.gov

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FunDaMos

Buenos Aires, Argentina

CEN Consultorios Especializados en Neurociencias

Córdoba, Argentina

Fundacion Lennox

Córdoba, Argentina

Instituto Medico DAMIC

Córdoba, Argentina

Sanatorio Prof Leon S Morra S A

Córdoba, Argentina

Instituto de Neurociencias San Agustin

La Plata, Argentina

C I A P Centro de investigacion y Asistencia en Psiquiatria

Rosario, Argentina

Anima

Alken, Belgium

Mental Health Center - Rousse

Rousse, Bulgaria

Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum

Sofia, Bulgaria

...and 49 more locations

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 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.

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 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.

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

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.

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 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.

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 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.

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)

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.

Time frame: Baseline (Day 1 of Study 54135419TRD3013) up to Week 104 of study 54135419TRD4010 (up to Week 136)

Secondary Outcomes

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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)

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.

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