Phase 3
Completed N=138
A Study to Evaluate the Efficacy, Safety, and Tolerability of Intranasal Esketamine Plus an Oral Antidepressant in Elderly Participants With Treatment-resistant Depression
Depressive Disorder, Treatment-Resistant
Source: ClinicalTrials.gov NCT02422186 ↗
Enrolled (actual)
138
Serious AEs
3.3%
Results posted
Apr 2019
Primary outcomePrimary: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- Mixed-Effects Model Using Repeated Measures (MMRM) Analysis — -10.0; -6.3 Units on a scale — p==0.059
Summary
The purpose of this study is to evaluate the efficacy and safety of switching elderly participants with treatment-resistant depression (TRD) from a prior antidepressant treatment (to which they have not responded) to either intranasal esketamine plus a new oral antidepressant or switching to a new oral antidepressant plus intranasal placebo.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- Mixed-Effects Model Using Repeated Measures (MMRM) Analysis |
-10.0; -6.3 | =0.059 |
| PRIMARY Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score to Endpoint (Double-blind Induction Phase [Day 28])- Analysis of Covariance (ANCOVA) Analysis |
-9.3; -5.6 | =0.052 |
| SECONDARY Percentage of Participants Who Achieved >=50% Reduction From Baseline in MADRS Total Score at Endpoint (Double-blind Induction Phase [Day 28]) (LOCF Data) |
23.9; 12.5 | — |
| SECONDARY Percentage of Participants in Remission (MADRS<=12) at Endpoint (Double-blind Induction Phase [Day 28]) (LOCF Data) |
15.5; 6.3 | — |
| SECONDARY Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis on Ranks |
-1.0; 0.0 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) to Endpoint (Double-blind Induction Phase [Day 28]): Health Status Index |
0.081; 0.026 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) to Endpoint (Double-blind Induction Phase [Day 28]): EQ-VAS |
6.2; 4.4 | — |
| SECONDARY Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) to Endpoint (Double-blind Induction Phase [Day 28]): Sum Score |
-6.6; -1.6 | — |
Eligibility Criteria
Inclusion Criteria
- At the time of signing the informed consent form (ICF), participant must be a man or woman 65 years of age or older
- At the start of the Screening/prospective observational 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 the start of the Screening/Prospective observational Phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated (IDS-C30) total score of greater than or equal to (>=) 31
- At the start of the Screening/Prospective observational Phase, participants must have had nonresponse (less than or equal to 25% improvement) to >=1 but less than or equal to (<=) 8 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and documented records by medical and pharmacy/prescription records, or a letter from the treating physician, for the current episode of depression
- Participant must be taking one of the oral antidepressant treatment with nonresponse that is documented on the MGH-ATRQ at the start of the screening/prospective observational phase
- The participant's current major depressive episode, depression symptom severity (Week 1 MADRS total score greater than or equal to 24 required) and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be confirmed for participation in a clinical study based on a Site-Independent Qualification Assessment
- Participant must be medically stable on the basis of clinical laboratory tests performed in the screening/prospective observational phase
Exclusion Criteria
- The participant's depressive symptoms have previously demonstrated nonresponse to: Esketamine or ketamine in the current major depressive episode per clinical judgment, or all of the 4 oral antidepressant treatment options available for the double-blind induction Phase (Duloxetine, Escitalopram, Sertraline, and Venlafaxine extended release [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 ECT
- Participants who has received vagal nerve stimulation (VNS) or who 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 psychosis, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current episode only), intellectual disability ( intellectual disability [DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319]), 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/prospective observational Phase, per the Investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS) and also includes history of suicidal behavior within the past year prior to start of the screening/prospective observational phase
- Participant has a history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related use disorder\
- Participant has a Mini Mental State Examination (MMSE) < 25 or <22 for those participants with less than an equivale
Data sourced from ClinicalTrials.gov (NCT02422186). 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.