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
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Esketamine 28 mg; Esketamine 56 mg; Esketamine 84 mg; Quetiapine XR 50 mg; Quetiapine XR 100 mg; Quetiapine XR 150 mg; SSRI/SNRI
Intervention description: Esketamine will be self-administered at a dose of 28 mg as nasal spray.; Esketamine will be self-administered at a dose of 56 mg as nasal spray.; Esketamine will be self-administered at a dose of 84 mg (maximum uptitrated dose) as nasal spray.; Quetiapine XR will be administered at an initial dose of 50 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.; Quetiapine XR will be administered at a dose of 100 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.; Quetiapine XR will be administered at a dose of 150 mg/day and may be further increased to 300 mg/day based on individual participant evaluation.; 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 SmPC (or local equivalent, if applicable).
Intervention MeSH terms: Quetiapine Fumarate; Esketamine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 676.0
Sex: All
Minimum age: 18 Years
Maximum age: 74 Years
Healthy volunteers: No

Summary:

      The primary purpose of this study is to evaluate the efficacy of flexibly dosed esketamine
      nasal spray compared with quetiapine extended-release (XR), both in combination with a
      continuing selective serotonin reuptake inhibitor/serotonin-norepinephrine reuptake inhibitor
      (SSRI/SNRI), in achieving remission in participants who have treatment-resistant major
      depressive disorder (MDD) with a current moderate to severe depressive episode.
    

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