Treatment-resistant Depression
Conditions
Interventions
167 participantes: Open-label induction phase: Direct entry participants start at a dose of 56 mg on Day 1. From Day 4 to 15, dose may be adjusted per protocol at investigator’s discretion based on ef
Optimization Phase: Direct-entry and transferred-entry participants will and self-administer intranasal esketamine (same dose) for first 4 weeks, then individualized to either once weekly or once ever
166 participants: Transferred-entry participant will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or o
Drug
Sponsors
Clinica Dr. Norton Sayeg Ltda. EPP
Janssen-Cilag Farmacêutica Ltda.
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
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 (=50% reduction in the MADRS total score from baseline [Day 1 pre-randomization] at the end of the 4-week double-blind induction phase)
Exclusion criteria
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 (CSSRS) - Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to relapse in Participants with stable remission who were randomized in the maintenance phase - Relapse is defined as any of the following: (1) MADRS total score ? 22 for 2 consecutive assessments separated by 5 to 15 days (inclusive); or (2) Hospitalization for worsening depression, for a suicide attempt or for suicide prevention. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Time to relapse in Participants with Stable Response (but not in stable remission) who were randomized in the maintenance phase - Time between participant randomization into the maintenance phase and the first documentation of a relapse event;Change From Baseline in MADRS total score at end of the Maintenance Phase in participants who were randomized in this 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.Change From Baseline in Subject-reported Depressive Symptoms Using the Patient Health Questionnaire-9 (PHQ-9) Total Score at End of the Maintenance Phase in participants who were randomized in this phase - The PHQ-9 is a 9-item scale used to assess depressive symptoms. Change From Baseline in Clinical Global Impression – Severity (CGI-S) Score at End of Maintenance Phase in participants who were randomized in this 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 at the time of rating. 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) Score at End of Maintenance Phase in participants who were randomized in this phase - The GAD-7 is a brief and validated measure of overall anxiety. Item responses are summed to yield a total score with range of 0 to 21, where higher scores indicate more anxiety. Change From Baseline in Subject-reported Healthrelated Quality of Life and Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ- 5D-5L) at End of Maintenance Phase in participants who were randomized in this phase - The EQ-5D-5L is a standardized instrument for use as a m | — |
Countries
Belgium, Brazil, Canada, Czech Republic, France, Germany, Hungary, Italy, Mexico, Poland, Spain, Turkey, United States
Contacts
Public ContactVinicius Righi
Janssen-Cilag Farmacêutica Ltda.
Outcome results
None listed