Phase 3
Completed N=676
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
Depressive Disorder, Major
Source: ClinicalTrials.gov NCT04338321 ↗
Enrolled (actual)
676
Serious AEs
5.4%
Results posted
Feb 2023
Primary outcomePrimary: Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 — 27.1; 17.6 Percentage of participants — p==0.003
◆ Published Evidence
Highly cited
186citations · ~62 / year
Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.
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.
Linked Publications (3)
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Esketamine Nasal Spray versus Quetiapine for Treatment-Resistant Depression.
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Esketamine Nasal Spray versus Quetiapine for Resistant Depression.
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Esketamine Nasal Spray versus Quetiapine for Resistant Depression.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Remission as Assessed by the Montgomery-Asberg Depression Rating Scale (MADRS) Score at Week 8 |
27.1; 17.6 | =0.003 sig |
| SECONDARY Percentage of Participants With Both Remission at Week 8 and Relapse-free Until Week 32 |
21.7; 14.1 | — |
| SECONDARY Change From Baseline in Clinician-rated Overall MADRS Score |
-5.3; -3.7; -9.0; -6.1; -12.8; -9.8 | — |
| SECONDARY Change From Baseline in Clinician-rated Overall MADRS Score at Last Observation Carried Forward (LOCF) |
-9.0; -5.8; -12.6; -8.9; -14.5; -10.7 | — |
| SECONDARY Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Severity (CGI-S) Scale Score |
-0.3; -0.2; -0.7; -0.5; -1.0; -0.7 | — |
| SECONDARY Change From Baseline in Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-S Scale Score at LOCF |
-0.7; -0.5; -1.0; -0.7; -1.3; -0.9 | — |
| SECONDARY Clinician-rated Overall Severity of Depressive Illness as Assessed by Clinical Global Impression - Change (CGI-C) Scale Score |
3.3; 3.6; 2.9; 3.3; 2.7; 3.1 | — |
| SECONDARY Number of Participants With Clinician-rated Overall Severity of Depressive Illness as Assessed by CGI-C Scale Score at LOCF |
6; 4; 97; 39; 141; 149 | — |
| SECONDARY Change From Baseline in Participant-reported Depressive Symptoms as Assessed by Patient Health Questionnaire (PHQ) 9-item Total Score |
-4.9; -3.1; -6.7; -5.0; -8.1; -6.1 | — |
| SECONDARY Change From Baseline in Participant-reported Depressive Symptoms as Assessed by PHQ 9-item Total Score at LOCF |
-4.9; -3.1; -6.6; -4.7; -7.8; -5.6 | — |
| SECONDARY Change From Baseline in Participant-reported Functional Impairment and Associated Disability as Assessed by Sheehan Disability Scale (SDS) Total Score |
-5.9; -4.1; -8.6; -6.8; -9.7; -8.6 | — |
| SECONDARY Change From Baseline in Participant-reported Functional Impairment and Associated Disability as Assessed by SDS Total Score at LOCF |
-5.9; -4.1; -8.2; -5.8; -9.0; -6.8 | — |
| SECONDARY Change From Baseline in Participant-reported Health-related Quality of Life (HRQoL) and Health Status as Assessed by 36-item Short-Form Health Survey (SF-36) Scale Score |
3.5; 2.2; 5.4; 3.8; 5.8; 4.7 | — |
| SECONDARY Change From Baseline in Participant-reported HRQoL and Health Status as Assessed by SF-36 Scale Score at LOCF |
5.1; 3.2; 5.3; 3.9; 5.6; 4.2 | — |
| SECONDARY Change From Baseline in Participant-reported Quality of Life as Assessed by Quality of Life in Depression Scale (QLDS) Total Score |
-8.9; -5.6; -12.0; -9.1; -13.5; -10.9 | — |
| SECONDARY Change From Baseline in Participant-reported Quality of Life as Assessed by QLDS Total Score at LOCF |
-8.9; -5.6; -11.3; -8.1; -12.3; -9.0 | — |
| SECONDARY Change From Baseline in Participant-reported Health-related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score: Health Status Index |
0.177; 0.124; 0.234; 0.206; 0.276; 0.227 | — |
| SECONDARY Change From Baseline in Participant-reported Health-related Quality of Life Group, as Assessed by EQ-5D-5L Score: Health Status Index at LOCF |
0.177; 0.124; 0.221; 0.175; 0.247; 0.187 | — |
| SECONDARY Change From Baseline in Participant-reported Health Status as Assessed by EQ-5D-5L Score: VAS |
13.3; 9.7; 18.9; 16.1; 20.9; 17.2 | — |
| SECONDARY Change From Baseline in Participant-reported Health Status as Assessed by EQ-5D-5L Score: VAS at LOCF |
13.3; 9.7; 18.2; 14.0; 19.4; 14.4 | — |
| SECONDARY Change From Baseline in Participant-reported Work Productivity as Assessed by Work Productivity and Activity Impairment (WPAI): Depression Questionnaire |
-11.95; -8.37; -19.02; -13.62; -21.87; -17.25 | — |
| SECONDARY Change From Baseline in Participant-reported Work Productivity as Assessed by WPAI: Depression Questionnaire at LOCF |
-11.95; -8.37; -18.28; -12.38; -20.23; -15.17 | — |
| SECONDARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
307; 262 | — |
| SECONDARY Number of Participants With TEAEs of Special Interest |
223; 140 | — |
| SECONDARY Number of Participants With Suicidal Ideation or Behavior as Assessed by Columbia-Suicide Severity Rating Scale (C-SSRS) Score |
22; 25; 0; 0; 21; 32 | — |
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 so
Data sourced from ClinicalTrials.gov (NCT04338321) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.