A Study of Esketamine Nasal Spray Versus Placebo Spray in Adult Participants With Treatment-resistant Depression
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorJanssen Research & Development, LLC
About this trial
The purpose of this study is to evaluate how well each individual dose of esketamine (56 milligrams \[mg\] and 84 mg) works when compared with placebo in improving depressive symptoms in participants with treatment resistant depression (individuals with major depressive disorder \[MDD\] who have not responded to at least 2 different antidepressant treatments given at an adequate dose for an adequate duration in the current episode of depression).
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Participant must meet the diagnostic and statistical manual of mental disorders (5th edition) (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single episode MDD, the duration of the episode must be greater than or equal to [>=] 12 months) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the mini international neuropsychiatric interview (MINI) as the primary diagnosis. Participant must have had the first onset of depression prior to 55 years of age
Participant must have had nonresponse (less than or equal to [<=] 25 percent [%] improvement) to >=2 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 a letter from a treating physician)
The participant's current major depressive episode, depression symptom severity, and antidepressant treatment response in the current depressive episode, must be confirmed by the state versus trait, assessability, face validity, ecological validity, rule of three P's (SAFER) Interview
Participant must be comfortable with self-administration of nasal spray medication and be able to follow the nasal spray administration instructions provided
Disqualifiers
The participant has used ketamine/esketamine (lifetime)
The participant's depressive symptoms have demonstrated nonresponse in the current major depressive episode to an adequate course of treatment with electroconvulsive therapy (ECT), defined as at least 7 treatments with unilateral/bilateral ECT, or to adequate course of treatment with transcranial magnetic stimulation (TMS), defined as at least 4 weeks of treatment with 5 sessions per week
Participant has received vagal nerve stimulation (VNS) or deep brain stimulation (DBS) in the current episode of depression
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), corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent) for suicidal ideation on the C-SSRS, or a history of suicidal behavior within the past year prior to the start of the screening phase. Participants reporting suicidal ideation with intent to act or suicidal behavior prior to the start of the double-blind treatment phase should be excluded
Trial design
Design model
Parallel
Treatments tested in this trial
Esketamine 56 mg
DrugParticipants will self-administer 56 mg of esketamine as intranasal spray into each nostril.
Esketamine 84 mg
DrugParticipants will self-administer 84 mg of esketamine as intranasal spray into each nostril.
Placebo
DrugParticipants will self-administer placebo as intranasal spray into each nostril.
Treatment groups
348 Participants
are divided into 3 treatment groupsGroup A: Esketamine 56 milligram (mg)Experimental treatment 2 interventions
Group B: Esketamine 84 mgExperimental treatment 2 interventions
Group C: PlaceboPlacebo comparator 3 interventions
Trial outcomes
Primary outcomes
1
Double-Blind (DB) Treatment Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 to the End of the 4-Week Double-Blind Treatment Phase
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Time frame
Baseline (Day 1 [prerandomization]) up to end of the 4-Week DB treatment phase (Day 28)Secondary outcomes
1
DB Treatment Phase: Change From Baseline in MADRS Total Score From Day 1 to Day 2
The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Time frame
Baseline (Day 1 [prerandomization]) up to Day 2 (approximately 24 hours after the first dose)2
DB Treatment Phase: Percentage of Responders in MADRS Over Time to the End of the 4-Week DB Treatment Phase
Percentage of responders (greater than or equal to \[\>=\] 50 percent \[%\] reduction from baseline in MADRS total score) over time to the end of the 4-week DB treatment phase will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)3
DB Treatment Phase: Percentage of Participants in Remission in MADRS Over Time to the End of the 4-Week DB Treatment Phase
Percentage of participants in remission (MADRS less than or equal to \[\<=\] 10 and MADRS \<= 12) over time to the end of the 4-week DB treatment phase will be reported. The MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment. The scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)4
DB Treatment Phase: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Over Time to the End of the 4-Week DB Treatment Phase
Change from baseline in CGI-S over time to the end of the 4-week DB treatment phase will be reported. The CGI-S is a clinician-rated scale that measures illness severity. The CGI has proved to be a robust measure of efficacy in many clinical drug trials and is easy and quick to administer. The CGI-S is rated on a 7-point scale, with the severity of illness scale using a range of responses from 1 (normal) through to 7 (among the most severely ill participants).
Time frame
Baseline up to end of the 4-Week DB treatment phase (Day 28)Other outcomes
1
DB Treatment Phase: Number of Participants with Abnormalities in Blood Oxygen Saturation (SpO2)
Number of participants who experience abnormally low blood oxygen saturation will be reported.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)2
DB Treatment Phase: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non-investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. TEAEs are defined as any adverse event occurring at or after the administration of study intervention.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)3
DB Treatment Phase: Suicidal Ideation and Behavior as Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
The C-SSRS is a clinical interview providing a summary of both ideation and behavior that can be administered during any evaluation or risk assessment to identify the level and type of suicidality present. The C-SSRS can also be used during treatment to monitor for clinical worsening.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)4
DB Treatment Phase: Number of Participants with Effects on Dissociative Symptoms As Measured Using the Clinician Administered Dissociative States Scale (CADSS)
The CADSS will be administered to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items, divided into 3 components: depersonalization (items 3-7, 20, 23), derealization (items 1-2, 8-13, 16-19, 21) and amnesia (items 14-15, 22). Participant's responses are coded on a 5-point scale (0 = "Not at all" through to 4 = "Extremely"). A higher score indicates a more severe condition.
Time frame
Up to end of the 4-Week DB treatment phase (Day 28)Sponsors and contacts
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Source ClinicalTrials.gov