Phase 3
Completed N=252
A Study to Evaluate the Efficacy, Pharmacokinetics, Safety and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression
Depressive Disorder, Treatment-Resistant
Source: ClinicalTrials.gov NCT03434041 ↗
Enrolled (actual)
252
Serious AEs
2.2%
Results posted
May 2022
Primary outcomePrimary: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) — -10.1; -8.1 Units on a Scale — p=0.123
◆ Published Evidence
No publication linked
No peer-reviewed publication reporting this trial's results has been linked yet. This can indicate results are unpublished — a known publication-bias signal. We re-check periodically.
Summary
The purpose of this study is to evaluate the efficacy of switching adult participants with treatment-resistant depression (TRD) from a prior antidepressant treatment (to which they have not responded) to flexibly dosed intranasal esketamine (56 milligram [mg] or 84 mg) plus a newly initiated oral antidepressant compared with switching to a newly initiated oral antidepressant (active comparator) plus intranasal placebo, in improving depressive symptoms. Efficacy will be assessed by the change from baseline in the Montgomery Asberg Depression Rating Scale (MADRS) total score from Day 1 (before randomization) to the end of the 4-week double-blind treatment phase.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to the End of Double-blind Treatment Phase (Day 28) |
-10.1; -8.1 | 0.123 |
| SECONDARY Change From Baseline in Depressive Symptoms as Measured by the MADRS Total Score to 24 Hours Post First Dose (Day 2) |
-8.0; -4.4 | — |
| SECONDARY Change From Baseline in Sheehan Disability Scale (SDS) Total Score to the End of Double-blind Treatment Phase (Day 28) |
-6.3; -5.3 | — |
| SECONDARY Percentage of Participants With Onset of Clinical Response |
6.5; 1.6 | — |
| SECONDARY Percentage of Responders at the End of Double-blind Treatment Phase (Day 28) |
19.3; 16.0 | — |
| SECONDARY Percentage of Participants in Remission at the End of Double-blind Treatment Phase (Day 28) |
12.8; 10.4 | — |
| SECONDARY Percentage of Participants With Sustained Remission |
5.6; 6.3 | — |
| SECONDARY Change From Baseline in Clinical Global Impression Severity (CGI-S) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) |
-1.0; -1.0 | — |
| SECONDARY Change From Baseline in Generalized Anxiety Disorder 7-item (GAD-7) Scale Score up to the Endpoint (Double-blind Treatment Phase [Day 28]) |
-4.3; -2.9 | — |
| SECONDARY Change From Baseline in Participant-Reported Health-Related Quality of Life as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score up to the Endpoint (Double-blind Treatment Phase [Day 28]): Health Status Index |
0.152; 0.103 | — |
| SECONDARY Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) Score up to the Endpoint (Double-blind Treatment Phase [Day 28]): Visual Analogue Scale (VAS) |
16.7; 11.9 | — |
| SECONDARY Change From Baseline in Participant-Reported Health Status as Assessed by EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to the Endpoint (Double-blind Treatment Phase [Day 28]): Sum Score |
-13.4; -9.5 | — |
Eligibility Criteria
Inclusion Criteria
- At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders-fifth edition (DSM-5) diagnostic criteria for recurrent major depressive disorder (MDD) or single-episode MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (mental status questionnaire) (MINI)
- At the start of the screening/prospective observational phase, participant must have had non-response (less than or equal to [ =1 but ) 2 years or not definable, upper limit is applicable to only the last 2 years) oral antidepressant treatments in the current episode of depression, assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and confirmed by documented records (for example, medical/ pharmacy/prescription records or letter from a treating physician). In addition, the participant is taking a different oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimum therapeutic dose
- The participant's current major depressive episode, depression symptom severity (Week 1 Montgomery-Asberg Depression Rating Scale [MADRS] total score >=28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using a Clinical-Validation Inventory for Study Admission (C-VISA)
- Participant must be medically stable on the basis of physical examination, medical history, vital signs (including blood pressure), pulse oximetry, and 12-lead electrocardiogram (ECG) performed in the screening/prospective observational phase. If there are any abnormalities that are not specified in the inclusion and exclusion criteria, they must be consistent with the underlying illness in the study population. This determination must be recorded in the participant's source documents and initialed or signed by the investigator
- Participant must be medically stable on the basis of clinical laboratory tests performed in the screening/prospective observational phase. If the results of the serum chemistry panel, hematology, or urinalysis are outside the normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the participant's source documents and initialed or signed by the investigator
Exclusion Criteria
- The participant's depressive symptoms have previously demonstrated non-response to:
- Esketamine or ketamine in the current major depressive episode per clinical judgment, or
- All of the oral antidepressant treatment options available in the respective country for the double-blind phase (that is, duloxetine, escitalopram, sertraline, and venlafaxine 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/bilateral ECT
- Participant has received 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 psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 315.8, 317, 318.0, 318.1, 318.2 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/prospecti
Data sourced from ClinicalTrials.gov (NCT03434041). 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.