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A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide

Primary Purpose

Major Depressive Disorder

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Esketamine

Placebo

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Major Depressive Disorder, Esketamine, Intranasal esketamine, Placebo

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder
Participants must have current suicidal ideation with intent
In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide
Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (>=) 22 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 (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25)

Exclusion Criteria:

Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder)
Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview
Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder
Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances
Participant has uncontrolled hypertension (systolic blood pressure greater than [>] 160 millimeter of mercury [mmHg] or diastolic blood pressure > 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Esketamine

Placebo

Arm Description

Esketamine hydrochloride solution (containing 14 milligram (mg) of esketamine base per 100 microliter [mcl] of intranasal spray) will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks. Dose may be reduced to 56 mg per day based on Investigator's discretion.

Matching Placebo solution will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks.

Outcomes

Primary Outcome Measures

Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)

The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The last observation carried forward (LOCF) approach was used for missing visit data in the ITT LOCF efficacy analyses.

Secondary Outcome Measures

Percentage of Participants With Sustained Response Based on MADRS Total Score (Double-blind Phase)

Sustained response is defined as a reduction from baseline in MADRS total score of greater than or equal to 50 percent, with onset on Day 1 that is maintained through the end of the double-blind phase (Day 25). The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses.

Change From Baseline to Day 2 in MADRS Total Score (Double-blind Phase)

The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses.

Change From Baseline to Double-blind Phase-End Point (Day 25) in MADRS Total Score (Double-blind Phase)

The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses. The last post baseline observation was carried forward as the "End Point" for the double-blind phase.

Percentage of Participants With Response Based on MADRS Total Score During the Double-Blind Phase

Percentage of participants with response (greater than or equal to (>=) 50% improvement from baseline in MADRS total score) during the double- blind phase was assessed. The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition.

Percentage of Participants With Response Based on MADRS Total Score at Follow up Phase Endpoint

Percentage of participants with response (greater than or equal to (>=) 50% improvement from baseline in MADRS total score) during the follow up was assessed. The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition.

Change From Baseline to Day 1: 4-hours Post-dose in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (CGJ-SR) Module 8 Score (Double-blind Phase)

SIBAT CGJ-SR: Module 8 operates numerous clinical global impression (CGI) severity scales used in other psychiatric studies. Changes in CGJ-SR designed to categorize clinically meaningful changes in clinician rated suicide risk from 'not at all suicidal' to 'participant is at imminent risk of suicide and immediate need for strong intervention (hospitalization with 24 hour 1:1 observation).' Patient scores for clinician-rated suicide risk: 0 (not suicidal); 1(occasional suicidal ideas, no intervention required);2(some clear suicidal ideas present),3(suicidal risk requires scheduled outpatient follow-up,no immediate intervention),4(suicidal risk requires immediate intervention, no hospitalization). 5( suicidal risk requires immediate hospitalization, no suicide precautions),6 (suicide risk requires hospitalization with suicide precautions). LOCF approach used for missing visit data in ITT LOCF efficacy analyses.

Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (SIBAT CGJ-SR) Module 8 Score (Double-blind Phase)

SIBAT CGJ-SR: Module 8 operates like numerous other CGI severity scales used in other psychiatric studies. Changes in CGJ-SR designed to categorize clinically meaningful changes in clinician rated suicide risk from 'not at all suicidal' to 'participant is at imminent risk of suicide and immediate need for strong intervention (hospitalization with 24 hour 1:1 observation).' Patient scores for clinician-rated suicide risk: 0 (not suicidal); 1(occasional suicidal ideas, no intervention required);2(some clear suicidal ideas present),3(suicidal risk requires scheduled outpatient follow-up,no immediate intervention),4(suicidal risk requires immediate intervention, no hospitalization). 5( suicidal risk requires immediate hospitalization, no suicide precautions),6 (suicide risk requires hospitalization with suicide precautions). LOCF approach used for missing visit data in ITT LOCF efficacy analyses.

Change From Baseline to Double-blind Phase-Endpoint (Day 25) Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (SIBAT CGJ-SR) Module 8 (Double-blind Phase)

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk Score (Follow-up Phase)

Change From Baseline to Day 1: 4- Hours Postdose in SIBAT-Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

SIBAT was specifically developed to measure rapid change in suicidality, based on concerns that existing scales such as Beck Scale for Suicidal Ideation (BSS) are not designed to discriminate differences associated with rapid change. Patient-rated section includes following modules: Module 1 (M-1)(demographic information,suicide history), M-2(current suicidal thinking),M-3 (protective factors), M-4 (suicide behavior),M-5(suicide risk),M-6(suicide-implicit association test).Patient-reported global assessment of suicide risk summarizes patient's judgment of suicide risk (Module 6). Scores: 0(None), 1(Very weak), 2(Weak), 3(Moderately weak), 4(Mild), 5(Moderate), 6 (Moderately strong), 7(Strong), 8(Extremely strong), 9(Extremely strong,constant). Negative change in score indicates improvement. LOCF approach used for missing visit data in the ITT LOCF efficacy analyses.

Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

SIBAT was specifically developed to measure rapid change in suicidality, based on concerns that existing scales such as BSS are not designed to discriminate differences associated with rapid change. Patient-rated section includes following modules: Module 1 (M-1)(demographic information,suicide history), M-2(current suicidal thinking),M-3 (protective factors), M-4 (suicide behavior),M-5(suicide risk),M-6(suicide-implicit association test).Patient-reported global assessment of suicide risk summarizes patient's judgment of suicide risk (Module 6). Scores: 0(None), 1(Very weak), 2(Weak), 3(Moderately weak), 4(Mild), 5(Moderate), 6 (Moderately strong), 7(Strong), 8(Extremely strong), 9(Extremely strong,constant). Negative change in score indicates improvement. LOCF approach used for missing visit data in the ITT LOCF efficacy analyses.

Change From Baseline to Double Blind Phase-Endpoint (Day 25) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Follow-up Phase)

Change From Baseline to Day 1: 4-Hours Postdose in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation. BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide, level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes,attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses.

Change From Baseline to Day 2 in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation. BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide,level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses.

Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Scale for Suicidal Ideation Total Score (Double-blind Phase)

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation.BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide, level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses. Last post baseline observation was carried forward as "End Point" for double-blind phase.

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Beck Scale for Suicidal Ideation Total Score (Follow-up Phase)

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation. BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide, level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses, last post baseline observation was carried forward as the "End Point" follow up phase.

Change From Baseline to Day 1: 4-Hours Postdose in Beck Hopelessness Scale (BHS) Total Score (Double-blind Phase)

BHS is paper-based self-reported measure to assess one's level of negative expectations or pessimism regarding future. Consists of 20 true-false items that examine the respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. Items fall within 3 domains: feelings about future; loss of motivation; future expectations. each response is assigned a score of 0 or 1. Total BHS score is sum of item responses, with range from 0 to 20, with a higher score representing higher level of hopelessness. Total scores that range from 0 to 3 are (normal range), scores 4 to 8 (mild hopelessness, scores 9 to 14 (moderate hopelessness), scores <14 (severe hopelessness). Negative change in score indicates improvement. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses.

Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Hopelessness Scale Total Score (Double-blind Phase)

Full Information

NCT ID

NCT02133001

First Posted

May 6, 2014

Last Updated

May 7, 2020

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT02133001

Brief Title

A Double-blind Study to Assess the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Participants Who Are Assessed to be at Imminent Risk for Suicide

Official Title

A Double-blind, Randomized, Placebo Controlled Study to Evaluate the Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Subjects Who Are Assessed to be at Imminent Risk for Suicide

Study Type

Interventional

2. Study Status

Record Verification Date

May 2020

Overall Recruitment Status

Completed

Study Start Date

May 23, 2014 (Actual)

Primary Completion Date

February 1, 2016 (Actual)

Study Completion Date

February 1, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram (mg) compared with intranasal placebo along with standard care treatment, in reducing the symptoms of major depressive disorder (MDD) (an affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities, the mood disturbance is prominent and relatively persistent), including the risk for suicide as assessed by the Investigator, in participants who will be assessed to be at imminent risk for suicide.

Detailed Description

This is a randomized (study medication assigned to participants by chance), double-blind (neither physician nor participant knows assigned study treatment), placebo-controlled (participants are randomly assigned to a test treatment or to an identical-appearing treatment that does not contain the test drug), and multicenter (when more than one hospital or medical school team works on a medical research study), study of esketamine in participants with major depressive disorder (MDD) in participants who will be 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 4 hours postdose on Day 1. The duration of study will be approximately 81 days per participant. The study consists of 3 parts: Screening (that is, with in 1 day before study commences on Day 1) and double-blind Treatment (from Day 1-25) and Follow-up (from Day 26 up to Day 81). All the eligible participants will be provided standard care treatment and will be randomly assigned to either esketmaine or placebo treatment. Esketamine/placebo will be administered by intranasal route (delivery of medications through the nasal mucosa) two times per week for 4 weeks. Efficacy of the participants will be primarily evaluated through MADRS. Participants' safety will be monitored throughout the study.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Major Depressive Disorder

Keywords

Major Depressive Disorder, Esketamine, Intranasal esketamine, Placebo

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

68 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Esketamine

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Matching Placebo solution will be administered by intranasal route using nasal spray pump as two times a week, for 4 weeks.

Intervention Type

Drug

Intervention Name(s)

Esketamine

Other Intervention Name(s)

Esketamine hydrochloride

Intervention Description

Esketamine 84 mg will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25). Dose may be reduced to 56 mg per day based on Investigator's discretion.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo will be self-administered by participants as intranasal spray as two times a week, for 4 weeks (that is, Day 1,4,8,11,15,18,22,25).

Primary Outcome Measure Information:

Title

Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-Predose) to Day 1: 4-hours post-dose

Secondary Outcome Measure Information:

Title

Percentage of Participants With Sustained Response Based on MADRS Total Score (Double-blind Phase)

Description

Time Frame

Day 1 to Day 25

Title

Change From Baseline to Day 2 in MADRS Total Score (Double-blind Phase)

Description

The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses.

Time Frame

Baseline (Day 1-predose) to Day 2

Title

Change From Baseline to Double-blind Phase-End Point (Day 25) in MADRS Total Score (Double-blind Phase)

Description

The MADRS consists of 10 items that cover all of the core depressive symptoms (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts). Each item is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptom). A total score (0 to 60) is calculated by adding the scores of all 10 items. For each item as well as the total score, a higher score represents a more severe condition. The LOCF approach was used for missing visit data in the ITT LOCF efficacy analyses. The last post baseline observation was carried forward as the "End Point" for the double-blind phase.

Time Frame

Baseline (Day 1-predose) to Double-blind Phase-End Point (Day 25)

Title

Percentage of Participants With Response Based on MADRS Total Score During the Double-Blind Phase

Description

Time Frame

Day 1 (4 hours postdose), Day 2 (double blind phase), Double blind phase -Endpoint (Day 25)

Title

Percentage of Participants With Response Based on MADRS Total Score at Follow up Phase Endpoint

Description

Time Frame

Follow up phase-endpoint (Day 81)

Title

Change From Baseline to Day 1: 4-hours Post-dose in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (CGJ-SR) Module 8 Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 1: 4-hours Postdose

Title

Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk (SIBAT CGJ-SR) Module 8 Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 2

Title

Description

Time Frame

Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25)

Title

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool (SIBAT)-Clinical Global Judgment of Suicide Risk Score (Follow-up Phase)

Description

Time Frame

Baseline (Day 1-predose) to Follow-up Phase-Endpoint (Day 81)

Title

Change From Baseline to Day 1: 4- Hours Postdose in SIBAT-Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 1: 4-hours postdose

Title

Change From Baseline to Day 2 in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 2

Title

Change From Baseline to Double Blind Phase-Endpoint (Day 25) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25)

Title

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Suicide Ideation and Behavior Assessment Tool Patient-Reported Global Assessment of Suicide Risk (Module 6) Score (Follow-up Phase)

Description

Time Frame

Baseline (Day 1-predose) to Follow-up Phase Endpoint (Day 81)

Title

Change From Baseline to Day 1: 4-Hours Postdose in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 1: 4-hours postdose

Title

Change From Baseline to Day 2 in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)

Description

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation. BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide,level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses.

Time Frame

Baseline (Day 1-predose) to Day 2

Title

Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Scale for Suicidal Ideation Total Score (Double-blind Phase)

Description

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation.BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide, level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses. Last post baseline observation was carried forward as "End Point" for double-blind phase.

Time Frame

Baseline (Day 1-predose) to Double-blind Phase-endpoint (Day 25)

Title

Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Beck Scale for Suicidal Ideation Total Score (Follow-up Phase)

Description

BSS is 21-item self-reported instrument to detect and measure severity of suicidal ideation. BSS measures broad spectrum of attitudes and behaviors associated with risk of suicide. Items in scale assess respondent's suicidal plans, deterrents to suicide, level of openness to revealing suicidal thoughts. First 19 items of scale measure gradations of severity of suicidal wishes, attitude, plans.Statements reflect increasing gradations of this severity,are scored from 0 to 2. Final two items ask about number of suicide attempts, seriousness of intention to die associated with last attempt,they are not used in calculating BSS total score. Total BSS score represents severity of suicide ideation, calculated by summing ratings of first 19 items;total score ranges from 0 to 38, with higher score representing greater suicide ideation. LOCF approach used for missing visit data in ITT LOCF efficacy analyses, last post baseline observation was carried forward as the "End Point" follow up phase.

Time Frame

Baseline (Day 1-predose) to Follow-up Phase-Endpoint (Day 81)

Title

Change From Baseline to Day 1: 4-Hours Postdose in Beck Hopelessness Scale (BHS) Total Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Day 1: 4-hours Postdose

Title

Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Hopelessness Scale Total Score (Double-blind Phase)

Description

Time Frame

Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Participants must meet Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for major depressive disorder Participants must have current suicidal ideation with intent In the Investigator's opinion, participant must be in need of acute psychiatric hospitalization due to imminent risk of suicide Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of greater than or equal to (>=) 22 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 (that is, through Day 5), and take prescribed non-investigational antidepressant therapy(ies) for at least the duration of the double-blind treatment phase (Day 25) Exclusion Criteria: Participant has a current clinical diagnosis of bipolar or related disorders, intellectual disability, or cluster b personality disorder (example, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, and narcissistic personality disorder) Participant meets DSM-IV criteria for borderline personality disorder, based on clinical interview Participant has a current or prior diagnosis of a psychotic disorder, major depressive disorder (MDD) with psychosis, or obsessive compulsive disorder Participant with a history or current signs and symptoms of liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, rheumatologic, or metabolic disturbances Participant has uncontrolled hypertension (systolic blood pressure greater than [>] 160 millimeter of mercury [mmHg] or diastolic blood pressure > 90 mmHg) despite diet, exercise or a stable dose of an allowed anti-hypertensive treatment at Screening; or any past history of hypertensive crisis

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Janssen Research & Development, LLC Clinical Trial

Organizational Affiliation

Janssen Research & Development, LLC

Official's Role

Study Director

Facility Information:

City

Birmingham

State/Province

Alabama

Country

United States

City

San Diego

State/Province

California

Country

United States

City

Hartford

State/Province

Connecticut

Country

United States

City

New Haven

State/Province

Connecticut

Country

United States

City

Atlanta

State/Province

Georgia

Country

United States

City

Iowa City

State/Province

Iowa

Country

United States

City

Baltimore

State/Province

Maryland

Country

United States

City

Towson

State/Province

Maryland

Country

United States

City

Ann Arbor

State/Province

Michigan

Country

United States

City

Rochester

State/Province

Minnesota

Country

United States

City

Cincinnati

State/Province

Ohio

Country

United States

City

Philadelphia

State/Province

Pennsylvania

Country

United States

City

Pittsburgh

State/Province

Pennsylvania

Country

United States

City

Houston

State/Province

Texas

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

33128208

Citation

Perez-Ruixo C, Rossenu S, Zannikos P, Nandy P, Singh J, Drevets WC, Perez-Ruixo JJ. Population Pharmacokinetics of Esketamine Nasal Spray and its Metabolite Noresketamine in Healthy Subjects and Patients with Treatment-Resistant Depression. Clin Pharmacokinet. 2021 Apr;60(4):501-516. doi: 10.1007/s40262-020-00953-4. Epub 2020 Oct 31.

Results Reference

derived

PubMed Identifier

29656663

Citation

Canuso CM, Singh JB, Fedgchin M, Alphs L, Lane R, Lim P, Pinter C, Hough D, Sanacora G, Manji H, Drevets WC. Efficacy and Safety of Intranasal Esketamine for the Rapid Reduction of Symptoms of Depression and Suicidality in Patients at Imminent Risk for Suicide: Results of a Double-Blind, Randomized, Placebo-Controlled Study. Am J Psychiatry. 2018 Jul 1;175(7):620-630. doi: 10.1176/appi.ajp.2018.17060720. Epub 2018 Apr 16.

Results Reference

derived

Links:

URL

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR103162&attachmentIdentifier=197ac6b4-787c-46b2-93a3-5bbc385b3a47&fileName=ESKETINSUI2001_(CR103162)_Additional_Results_Data_CH.pdf&versionIdentifier=

Description

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