Phase 3
Completed N=779
A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression
Source: ClinicalTrials.gov NCT02497287 ↗Enrolled (actual)
779
Serious AEs
3.6%
Results posted
Apr 2019
Primary outcomePrimary: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) — 90.1 Percentage of participants
◆ Published Evidence
Emerging
15citations · ~4 / year
Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.
Summary
The purpose of this open-label, multicenter study is to assess the long term safety and efficacy of intranasal esketamine plus an oral antidepressant in participants with treatment-resistant depression (TRD).
Linked Publications (5)
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Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression.
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Adverse Events and Measurement of Dissociation After the First Dose of Esketamine in Patients With TRD.
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Indirect adjusted comparison of 6-month clinical outcomes between esketamine nasal spray and other real-world polypharmacy treatment strategies for treatment resistant depression: results from the ICEBERG study.
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ICEBERG study: an indirect adjusted comparison estimating the long-term benefit of esketamine nasal spray when compared with routine treatment of treatment resistant depression in general psychiatry.
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Estimating the benefit of esketamine nasal spray versus real-world treatment on patient-reported functional remission: results from the ICEBERG study.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) |
90.1 | — |
| PRIMARY Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders |
0.6; 8.1; 10.5; 17.0 | — |
| PRIMARY Change From Baseline in Cognitive Test Battery: Detection Test (DET) Score |
-0.0028 | — |
| PRIMARY Change From Baseline in Cognitive Test Battery: Identification Test (IDN) Score |
-0.0083 | — |
| PRIMARY Change From Baseline in Cognitive Test Battery: One Card Learning Test (OCL) Score |
0.0502 | — |
| PRIMARY Change From Baseline in Cognitive Test Battery: One Back Test (ONB) Score |
0.0177 | — |
| PRIMARY Change From Baseline in Cognitive Test Battery: Groton Maze Learning Test (GMLT) Score |
6.9 | — |
| PRIMARY Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Total Recall |
2.8 | — |
| PRIMARY Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Delayed Recall |
0.8 | — |
| PRIMARY Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Number of Words Recalled |
0.3 | — |
| PRIMARY Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Recognition Discrimination Index |
0.5 | — |
| SECONDARY Change From Baseline to Endpoint in Montgomery Asberg Depression Rating Scale (MADRS) Total Score During Induction (IND) Phase |
-16.4 | — |
| SECONDARY Change From Baseline to Endpoint in MADRS Total Score During Optimization/Maintenance (OP/MA) Phase |
0.3 | — |
| SECONDARY Change From Baseline to Endpoint in Patient Health Questionnaire - 9 (PHQ-9) Total Score During IND Phase |
-8.9 | — |
| SECONDARY Change From Baseline to Endpoint in PHQ-9 Total Score During OP/MA Phase |
-0.2 | — |
| SECONDARY Change From Baseline to Endpoint in Clinical Global Impression of Severity (CGI-S) Scale Score During IND Phase |
-2.0 | — |
| SECONDARY Change From Baseline to Endpoint in CGI-S Scale Score During OP/MA Phase |
0.0 | — |
| SECONDARY Change From Baseline to Endpoint in Generalized Anxiety Disorder (GAD-7) Total Score During IND Phase |
-5.9 | — |
| SECONDARY Change From Baseline to Endpoint in GAD-7 Total Score During OP/MA Phase |
0.2 | — |
| SECONDARY Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During IND Phase: Sum Score |
-15.3 | — |
| SECONDARY Change From Baseline to Endpoint in EQ-5D-5L Score During IND Phase: EQ-VAS |
17.0 | — |
| SECONDARY Change From Baseline to Endpoint in EQ-5D-5L Scale Score During IND Phase: Health Status Index |
0.190 | — |
| SECONDARY Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During OP/MA Phase: Sum Score |
-0.7 | — |
| SECONDARY Change From Baseline to Endpoint in EQ-5D-5L Score During OP/MA Phase: EQ-VAS |
1.6 | — |
| SECONDARY Change From Baseline to Endpoint in EQ-5D-5L Scale Score During OP/MA Phase: Health Status Index |
-0.009 | — |
| SECONDARY Change From Baseline in Sheehan Disability Scale (SDS) Total Score During IND Phase |
-9.3 | — |
| SECONDARY Change From Baseline in Sheehan Disability Scale Total Score During OP/MA Phase |
-1.6 | — |
| SECONDARY Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase |
11.6; 25.0; 42.8; 78.4 | — |
| SECONDARY Percentage of Participants With Response as Assessed by PHQ-9 Total Score During IND Phase |
37.2; 62.0 | — |
| SECONDARY Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase |
7.3; 15.6; 27.2; 47.2 | — |
| SECONDARY Percentage of Participants With Remission as Assessed by PHQ-9 Total Score During IND Phase |
12.7; 26.9 | — |
| SECONDARY Percentage of Participants With an Increase Score From Predose at Any Time in Clinician-Administered Dissociative States Scale (CADSS) Total Score During IND Phase |
92.0 | — |
| SECONDARY Percentage of Participants With an Increase Score From Predose at Any Time in CADSS Total Score During OP/MA Phase |
86.1 | — |
| SECONDARY Percentage of Participants With Treatment-Emergent Acute Hypertension (Systolic and Diastolic) During IND and OP/MA Phases |
2.2; 2.4; 4.1 | — |
Eligibility Criteria
Inclusion Criteria
A). For Direct-Entry Participants
- 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)
- At the start of the screening 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 screening, participant must have a MADRS total score of >=22
- At the start of the screening phase, participants must have had nonresponse to >=2 oral antidepressant treatments in the current episode of depression, as assessed using the the MGHATRQ and confirmed by documented records (example medical/pharmacy/prescription records or a letter from treating a physician, etc,) B). For Transferred-entry Participants
- All participants who completed the double-blind induction phase of ESKETINTRD3005 study, regardless of their response status, will be eligible to participate in this study, if they meet the study specific eligibility criteria
Exclusion Criteria
A). For Direct-Entry Participants
- Participant's depressive symptoms have previously not responded to: Esketamine or ketamine in the current major depressive episode per clinical judgment or All of the 4 oral antidepressant treatment options available in the respective country for the open-label induction phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine XR) in the current major depressive episode (based on Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire [ MGH-ATRQ])
- Participant 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), 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, 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 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
- Participants who has a Mini Mental State Examination (MMSE) <25; Has neurodegenerative disorder (example, Alzheimer's disease, vascular dementia, Parkinson's disease), or evidence of mild cognitive impairment (MCI) B). Transferred-Entry Participants
- Participant has taken any prohibited therapies that would not permit dosing on Day 1
Data sourced from ClinicalTrials.gov (NCT02497287) 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.