Phase 3
Completed N=226
54135419SUI3001: A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide
Depressive Disorder, Major
Source: ClinicalTrials.gov NCT03039192 ↗
Enrolled (actual)
226
Serious AEs
4.4%
Results posted
Oct 2020
Primary outcomePrimary: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase — -12.8; -16.4 units on a scale — p=0.006
◆ Published Evidence
Established
97citations · ~19 / year
Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.
Summary
The purpose of the study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo in addition to comprehensive standard of care in reducing the symptoms of Major Depressive Disorder (MDD), including suicidal ideation, in participants who are assessed to be at imminent risk for suicide, as measured by the change from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24 hours post first dose.
Linked Publications (5)
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Ketamine and other glutamate receptor modulators for depression in adults with unipolar major depressive disorder.
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Esketamine versus placebo on time to remission in major depressive disorder with acute suicidality.
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Effects of esketamine on patient-reported outcomes in major depressive disorder with active suicidal ideation and intent: a pooled analysis of two randomized phase 3 trials (ASPIRE I and ASPIRE II).
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Treatment response to esketamine nasal spray in patients with major depressive disorder and acute suicidal ideation or behavior without evidence of early response: a pooled post hoc analysis of ASPIRE.
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Assessing the meaningful change threshold of Quality of Life in Depression Scale using data from two phase 3 studies of esketamine nasal spray.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase |
-12.8; -16.4 | 0.006 sig |
| SECONDARY Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase |
-1.0; -1.0 | — |
| SECONDARY Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [<=] 12) Through the Double-blind Phase |
9; 12; 10; 21; 13; 28 | — |
| SECONDARY Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase |
-10.9; -13.5; -12.9; -16.4; -14.5; -19.1 | — |
| SECONDARY Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase |
0.0; -1.0; -1.0; -1.0; -1.0; -2.0 | — |
| SECONDARY Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase |
25; 37; 39; 42; 45; 49 | — |
| SECONDARY Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase |
0.0; -1.0; -1.0; -1.0; -1.0; -2.0 | — |
| SECONDARY Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase |
-4.4; -5.3; -6.6; -6.9 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index |
0.096; 0.156; 0.169; 0.206; 0.189; 0.227 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS) |
7.8; 13.5; 16.3; 17.9; 20.0; 21.4 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score |
-6.1; -11.2; -12.3; -15.2; -13.4; -16.8 | — |
| SECONDARY Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase |
-2.5; -3.1; -4.4; -5.6; -5.6; -6.8 | — |
| SECONDARY Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase |
51.7; 63.5; 57.6; 65.8; 70.9; 70.5 | — |
| SECONDARY Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase |
0.0; 0.0; -1.0; -1.0; -1.0; -1.0 | — |
| SECONDARY Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 - Clinician-rated FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase |
-1.0; -1.0; -1.0; -1.0; -1.0; -2.0 | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase |
83; 100 | — |
| SECONDARY Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase |
1; 1; 1; 1; 0; 0 | — |
| SECONDARY Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase |
0; 1; 0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase |
8; 2; 4; 5; 3; 5 | — |
| SECONDARY Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [<] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase |
2; 1 | — |
| SECONDARY Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase |
2; 3; 6; 13; 4; 0 | — |
| SECONDARY Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase |
0; 3; 1; 13; 20; 43 | — |
| SECONDARY Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase |
34; 95; 23; 84; 29; 81 | — |
Eligibility Criteria
Inclusion Criteria
- Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th edition) (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Psychiatric Interview (MINI)
- In the physician's opinion, acute psychiatric hospitalization is clinically warranted due to participant's imminent risk of suicide
- Participants must have current suicidal ideation with intent, confirmed by a "Yes" response to Question B3 [Think (even momentarily) about harming or of hurting or of injuring yourself: with at least some intent or awareness that you might die as a result; or think about suicide (ie, about killing yourself)?] and Question B10 [Intend to act on thoughts of killing yourself?] obtained from the MINI. Note: the response to B3 must refer to the present, whereas the response to B10 may reflect the past 24 hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of MINI must be repeated prior to randomization to confirm eligibility
- Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than (>) 28 predose on Day 1
- As part of standard of care treatment, participant agrees to be hospitalized voluntarily for a recommended period of 5 days after randomization (may be shorter or longer if clinically warranted in the investigator's opinion) and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)
- Participant is comfortable with self-administration of intranasal medication and able to follow instructions provided
Exclusion Criteria
- Participant has a current DSM-5 diagnosis of bipolar (or related disorders), antisocial personality disorder, or obsessive compulsive disorder
- Participant currently meets DSM-5 criteria for borderline personality disorder. Participant not meeting full DSM-5 criteria for borderline personality disorder but exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should also be excluded
- Participant has a current clinical diagnosis of autism, dementia, or intellectual disability
- Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD with psychotic features
- Participant meets the DSM-5 severity criteria for moderate or severe substance or alcohol use disorder, (except for nicotine or caffeine), within the 6 months before screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder is exclusionary
Data sourced from ClinicalTrials.gov (NCT03039192) 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.