Treatment-resistant Depression
Conditions
Interventions
Escetamine group
98 participants
Participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen in the Double-Blind Induction Phase. All participants will start at a dose of 56 mg on D
no dose increase permitted. After Day 15, dose must remain stable (unchanged)
Control Group
participants will simultaneously initiate a new, open-label oral antidepressant (duloxetine, escitalopram, sertraline, or venlafaxine extended release [XR]) on Day 1 that will be continued for the dur
Drug
Sponsors
Centro De Psiquiatria E Pesquisas Sandra Ruschel Ltda
Janssen-Cilag Farmacêutica Ltda.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: At the time of signing the informed consent form (ICF), participant must be a man or woman 18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than [>]18) to 64 years of age, inclusive - At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) 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 Mini- International Neuropsychiatric Interview (MINI) - At the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (>=) 34 - At the start of the screening/prospective observational phase, participants must have had nonresponse to >=2 but less than or equal to (<=) 5 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented by medical history and pharmacy/prescription records, for the current episode of depression: Subject must be taking an oral antidepressant treatment with nonresponse at the start of the screening/prospective observational phase - The participant’s current major depressive episode and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be deemed valid for participation in a clinical study based on a Site-Independent Qualification Assessment
Exclusion criteria
Exclusion criteria: Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (ie, duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the current major depressive episode (based on MGH-ATRQ), 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 - Participant currently has an implant for vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression - Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychosis, bipolar or related disorders (confirmed by the MINI), comorbid obsessive compulsive disorder, intellectual disability (only DSM-5 diagnostic code 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 (C-SSRS) – Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score at End of Double-blind Induction Phase - The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The MADRS evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts. | — |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Subject reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ- 9) Total Score at End of Doubleblind Induction Phase - The PHQ-9 is a 9-item scale used to assess depressive symptoms.; 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 - The SDS is a subject-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. ; Change From Baseline in Clinical Global Impression – Severity (CGI-S) Score at End of Double-blind Induction Phase - The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness. The CGI-S permits a global evaluation of the participant’s condition at a given time; Change From Baseline in Subject reported Generalized Anxiety Disorder (GAD-7) Total Score at End of Doubleblind Induction Phase - The GAD-7 is a brief and validated measure of overall anxiety.; Change From Baseline in Subjectreported Healthrelated Quality of Life and Health Status as Assessed by EuroQol- 5 Dimension-5 Level (EQ-5D-5L) at End ofDouble-blind Induction Phase - The EQ-5D-5L is a standardized instrument for use as a measure of health outcome, primarily designed for self-completion by respondents.; Onset of Clinical Response is defined as greater than or equal to (>=) 50% improvement in MADRS total score by the day after taking the first dose [ie, Day 2] of double blind intranasal medication, that is sustained through the end of the 4-week double-blind induction phase | — |
Countries
Brazil, Czech Republic, Germany, Poland, Spain, United States
Contacts
Public ContactVinicius Righi
Janssen-Cilag Farmacêutica Ltda.
Outcome results
None listed