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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

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ClinicalTrials.gov Identifier: NCT02133001
Recruitment Status : Completed
First Posted : May 7, 2014
Results First Posted : April 24, 2019
Last Update Posted : April 24, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: Esketamine
Drug: Placebo
Enrollment 68
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Period Title: Double Blind (Day 1-25)
Started 32 36
Safety 31 35
Completed 22 [1] 27 [1]
Not Completed 10 9
Reason Not Completed
Adverse Event             1             5
Lack of Efficacy             4             1
Lost to Follow-up             2             0
Other             2             2
Withdrawal by Subject             1             1
[1]
Participants who completed continued to follow-up phase.
Period Title: Follow-Up Phase (Day 26-81)
Started 22 27
Completed 20 24
Not Completed 2 3
Reason Not Completed
Lost to Follow-up             1             1
Withdrawal by Subject             1             1
Other             0             1
Arm/Group Title Placebo Esketamine 84 mg Total
Hide Arm/Group Description Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase. Total of all reporting groups
Overall Number of Baseline Participants 31 35 66
Hide Baseline Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 31 participants 35 participants 66 participants
36  (12.82) 35.7  (13.4) 35.8  (13.03)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 31 participants 35 participants 66 participants
Female
21
  67.7%
22
  62.9%
43
  65.2%
Male
10
  32.3%
13
  37.1%
23
  34.8%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 31 participants 35 participants 66 participants
31
 100.0%
35
 100.0%
66
 100.0%
1.Primary Outcome
Title Change From Baseline to Day 1: 4-Hour Post-dose in Montgomery Asberg Depression Rating Scale (MADRS) Total Score (Double-blind Phase)
Hide 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 last observation carried forward (LOCF) approach was used for missing visit data in the ITT LOCF efficacy analyses.
Time Frame Baseline (Day 1-Predose) to Day 1: 4-hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-9.1  (8.38) -13.4  (9.03)
2.Secondary Outcome
Title Percentage of Participants With Sustained Response Based on MADRS Total Score (Double-blind Phase)
Hide Description 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.
Time Frame Day 1 to Day 25
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Measure Type: Number
Unit of Measure: Percentage of participants
6.7 11.8
3.Secondary Outcome
Title Change From Baseline to Day 2 in MADRS Total Score (Double-blind Phase)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-12.8  (9.77) -19.3  (12.02)
4.Secondary Outcome
Title Change From Baseline to Double-blind Phase-End Point (Day 25) in MADRS Total Score (Double-blind Phase)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Mean (Standard Deviation)
Unit of Measure: units on a scale
-23.0  (10.83) -26.4  (14.52)
5.Secondary Outcome
Title Percentage of Participants With Response Based on MADRS Total Score During the Double-Blind Phase
Hide Description 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.
Time Frame Day 1 (4 hours postdose), Day 2 (double blind phase), Double blind phase -Endpoint (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4-hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Measure Type: Number
Unit of Measure: Percentage of participants
Day 1 (4 hours postdose) 12.9 25.7
Day 2 (double blind phase) 29.0 54.3
Double blind phase -Endpoint (Day 25) 54.8 74.3
6.Secondary Outcome
Title Percentage of Participants With Response Based on MADRS Total Score at Follow up Phase Endpoint
Hide Description 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.
Time Frame Follow up phase-endpoint (Day 81)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Follow Up phase) analysis set was defined as all participants who had at least one measurement of MADRS total score during the follow up phase.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 22 27
Measure Type: Number
Unit of Measure: Percentage of participants
63.6 66.7
7.Secondary Outcome
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)
Hide Description 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.
Time Frame Baseline (Day 1-predose) to Day 1: 4-hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score. Here N (overall number of participants analyzed)signifies number of participants who were evaluable for this endpoint.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 33
Median (Full Range)
Unit of Measure: Units on a scale
0
(-5 to 1)
0
(-6 to 1)
8.Secondary Outcome
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)
Hide Description 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.
Time Frame Baseline (Day 1-predose) to Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Median (Full Range)
Unit of Measure: Units on a scale
0
(-6 to 0)
-1.0
(-6 to 1)
9.Secondary Outcome
Title 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)
Hide Description 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. Last post baseline observation was carried forward as “End Point” for the double-blind phase.
Time Frame Baseline (Day 1-predose) to Double-blind Phase-Endpoint (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Median (Full Range)
Unit of Measure: Units on a scale
-5.0
(-6 to 0)
-5.0
(-6 to 0)
10.Secondary Outcome
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)
Hide Description 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. Last post baseline observation was carried forward as “End Point” for follow up phase.
Time Frame Baseline (Day 1-predose) to Follow-up Phase-Endpoint (Day 81)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Follow Up phase) analysis set was defined as all participants who had at least one measurement of MADRS total score during the follow up phase.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 22 27
Median (Full Range)
Unit of Measure: Units on a scale
-5.0
(-6 to -3)
-5.0
(-6 to -2)
11.Secondary Outcome
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)
Hide Description 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.
Time Frame Baseline (Day 1-predose) to Day 1: 4-hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Median (Full Range)
Unit of Measure: Units on scale
-1.0
(-6 to 3)
-1.0
(-7 to 2)
12.Secondary Outcome
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)
Hide Description 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.
Time Frame Baseline (Day 1-predose) to Day 2
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Median (Full Range)
Unit of Measure: Units on a scale
-1.5
(-7 to 1)
-2
(-8 to 0)
13.Secondary Outcome
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)
Hide Description 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. 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)
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-To-Treat Analysis (ITT) analysis set defined as all randomized participants who received at least 1 dose of study medication during the double-blind phase and had both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 35
Mean (Full Range)
Unit of Measure: Units on a scale
-3.0
(-9 to 1)
-4.0
(-8 to 0)
14.Secondary Outcome
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)
Hide Description 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 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Follow Up phase) analysis set was defined as all participants who had at least one measurement of MADRS total score during the follow up phase.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 22 27
Median (Full Range)
Unit of Measure: Units on a scale
-4.0
(-9 to 0)
-3.0
(-9 to 0)
15.Secondary Outcome
Title Change From Baseline to Day 1: 4-Hours Postdose in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)
Hide 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 1: 4-hours postdose
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-8.3  (7.12) -10.2  (9.74)
16.Secondary Outcome
Title Change From Baseline to Day 2 in Beck Scale for Suicidal Ideation (BSS) Total Score (Double-blind Phase)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1, 4-hour post dose evaluation for the MADRS total score. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-10.7  (7.73) -12.9  (9.63)
17.Secondary Outcome
Title Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Scale for Suicidal Ideation Total Score (Double-blind Phase)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1, 4-hour post dose evaluation for the MADRS total score. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 31 34
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-16.0  (10.54) -19.3  (9.61)
18.Secondary Outcome
Title Change From Baseline to Follow-up Phase-Endpoint (Day 81) in Beck Scale for Suicidal Ideation Total Score (Follow-up Phase)
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
The ITT (Follow Up phase) analysis set was defined as all participants who had at least one measurement of MADRS total score during the follow up phase. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 22 26
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-18.0  (9.92) -20.3  (8.02)
19.Secondary Outcome
Title Change From Baseline to Day 1: 4-Hours Postdose in Beck Hopelessness Scale (BHS) Total Score (Double-blind Phase)
Hide Description 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.
Time Frame Baseline (Day 1-predose) to Day 1: 4-hours Postdose
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1, 4-hour post dose evaluation for the MADRS total score. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 30 35
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-3.1  (5.71) -4.1  (5.63)
20.Secondary Outcome
Title Change From Baseline to Double-blind Phase-Endpoint (Day 25) in Beck Hopelessness Scale Total Score (Double-blind Phase)
Hide Description 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. 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-Endpoint (Day 25)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT analysis set: all randomized participants who received at least 1 dose of study medication during the double-blind phase and have both the baseline and the Day 1-4 hour post dose evaluation for the MADRS total score. Here 'N' signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Esketamine 84 mg
Hide Arm/Group Description:
Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 weeks on days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase.
Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment (determined by the treating physician based on clinical judgment) on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase.
Overall Number of Participants Analyzed 30 35
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-7.7  (7.81) -10.3  (5.51)
Time Frame Up to Day 81
Adverse Event Reporting Description Safety analysis set included all randomized participants who receive at least 1 dose of study drug in the double-blind phase. Safety (FU) analysis set included all participants who had at least 1 visit during the follow-up phase.
 
Arm/Group Title Double Blind (Day 1-25): Placebo Double Blind (Day 1-25): Esketamine 84 mg Follow Up Phase (Day 26-81): Placebo Follow Up Phase (Day 26-81): Esketamine 84 mg
Hide Arm/Group Description Participants received intranasal placebo (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) administered twice weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25 along with standard of care antidepressant treatment determined by the treating physician based on clinical judgment on Day 1 and continued for the duration of the double-blind treatment phase. Participants self-administered 1 spray into each nostril (1 spray in each nostril at 0, 5 and 10 minutes using 3 devices on a single day) of Esketamine 84 milligram (mg) twice Weekly for 4 Weeks on Days 1, 4, 8, 11, 15, 18, 22, and Day 25 along with standard of care antidepressant treatment determined by the treating physician based on clinical judgment on Day 1 and continued for the duration of the double-blind treatment phase. After Day 1, a single dose reduction from esketamine 84 mg to esketamine 56 mg was permitted if a participant was unable to tolerate the intranasal esketamine 84 mg. Participants continued to receive the reduced dose for the duration of the double-blind treatment phase. Participants who completed the double blind treatment phase were continued to follow-up phase for 81 days. Participants who completed the double blind treatment phase were continued to follow-up phase for 81 days.
All-Cause Mortality
Double Blind (Day 1-25): Placebo Double Blind (Day 1-25): Esketamine 84 mg Follow Up Phase (Day 26-81): Placebo Follow Up Phase (Day 26-81): Esketamine 84 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Double Blind (Day 1-25): Placebo Double Blind (Day 1-25): Esketamine 84 mg Follow Up Phase (Day 26-81): Placebo Follow Up Phase (Day 26-81): Esketamine 84 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/31 (0.00%)   4/35 (11.43%)   5/22 (22.73%)   1/27 (3.70%) 
Infections and infestations         
Cellulitis * 1  0/31 (0.00%)  0/35 (0.00%)  1/22 (4.55%)  0/27 (0.00%) 
Psychiatric disorders         
Agitation * 1  0/31 (0.00%)  1/35 (2.86%)  0/22 (0.00%)  0/27 (0.00%) 
Depressive Symptom * 1  0/31 (0.00%)  1/35 (2.86%)  0/22 (0.00%)  0/27 (0.00%) 
Suicidal Ideation * 1  0/31 (0.00%)  2/35 (5.71%)  1/22 (4.55%)  1/27 (3.70%) 
Suicide Attempt * 1  0/31 (0.00%)  0/35 (0.00%)  3/22 (13.64%)  0/27 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 18.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Double Blind (Day 1-25): Placebo Double Blind (Day 1-25): Esketamine 84 mg Follow Up Phase (Day 26-81): Placebo Follow Up Phase (Day 26-81): Esketamine 84 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/31 (80.65%)   30/35 (85.71%)   6/22 (27.27%)   11/27 (40.74%) 
Ear and labyrinth disorders         
Hyperacusis * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Tinnitus * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Vertigo * 1  0/31 (0.00%)  4/35 (11.43%)  0/22 (0.00%)  0/27 (0.00%) 
Eye disorders         
Blepharospasm * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Diplopia * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Vision Blurred * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Gastrointestinal disorders         
Abdominal Pain * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  1/27 (3.70%) 
Constipation * 1  3/31 (9.68%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Diarrhoea * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  1/27 (3.70%) 
Dry Mouth * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  2/27 (7.41%) 
Flatulence * 1  2/31 (6.45%)  1/35 (2.86%)  0/22 (0.00%)  0/27 (0.00%) 
Hypoaesthesia Oral * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Nausea * 1  1/31 (3.23%)  13/35 (37.14%)  1/22 (4.55%)  0/27 (0.00%) 
Paraesthesia Oral * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Toothache * 1  2/31 (6.45%)  0/35 (0.00%)  1/22 (4.55%)  0/27 (0.00%) 
Vomiting * 1  0/31 (0.00%)  7/35 (20.00%)  0/22 (0.00%)  1/27 (3.70%) 
General disorders         
Fatigue * 1  1/31 (3.23%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Feeling Abnormal * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Feeling Cold * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Infections and infestations         
Cellulitis * 1  0/31 (0.00%)  0/35 (0.00%)  2/22 (9.09%)  0/27 (0.00%) 
Pharyngitis * 1  0/31 (0.00%)  0/35 (0.00%)  0/22 (0.00%)  2/27 (7.41%) 
Upper Respiratory Tract Infection * 1  2/31 (6.45%)  0/35 (0.00%)  1/22 (4.55%)  1/27 (3.70%) 
Investigations         
Blood Pressure Increased * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Weight Increased * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Nervous system disorders         
Dizziness * 1  4/31 (12.90%)  12/35 (34.29%)  0/22 (0.00%)  1/27 (3.70%) 
Dizziness Postural * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Dysgeusia * 1  5/31 (16.13%)  11/35 (31.43%)  0/22 (0.00%)  1/27 (3.70%) 
Headache * 1  8/31 (25.81%)  11/35 (31.43%)  2/22 (9.09%)  2/27 (7.41%) 
Hypoaesthesia * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Paraesthesia * 1  1/31 (3.23%)  6/35 (17.14%)  0/22 (0.00%)  0/27 (0.00%) 
Sedation * 1  2/31 (6.45%)  6/35 (17.14%)  0/22 (0.00%)  1/27 (3.70%) 
Somnolence * 1  2/31 (6.45%)  4/35 (11.43%)  1/22 (4.55%)  0/27 (0.00%) 
Tremor * 1  1/31 (3.23%)  1/35 (2.86%)  0/22 (0.00%)  2/27 (7.41%) 
Psychiatric disorders         
Agitation * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Anxiety * 1  1/31 (3.23%)  6/35 (17.14%)  0/22 (0.00%)  0/27 (0.00%) 
Dissociation * 1  4/31 (12.90%)  11/35 (31.43%)  0/22 (0.00%)  0/27 (0.00%) 
Euphoric Mood * 1  2/31 (6.45%)  4/35 (11.43%)  0/22 (0.00%)  0/27 (0.00%) 
Insomnia * 1  2/31 (6.45%)  3/35 (8.57%)  0/22 (0.00%)  3/27 (11.11%) 
Panic Attack * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Renal and urinary disorders         
Pollakiuria * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Epistaxis * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  1/27 (3.70%) 
Intranasal Paraesthesia * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Nasal Congestion * 1  2/31 (6.45%)  1/35 (2.86%)  0/22 (0.00%)  1/27 (3.70%) 
Nasal Discomfort * 1  1/31 (3.23%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Oropharyngeal Pain * 1  1/31 (3.23%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Pharyngeal Hypoaesthesia * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Rhinalgia * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Rhinorrhoea * 1  2/31 (6.45%)  0/35 (0.00%)  0/22 (0.00%)  0/27 (0.00%) 
Throat Irritation * 1  0/31 (0.00%)  3/35 (8.57%)  0/22 (0.00%)  0/27 (0.00%) 
Skin and subcutaneous tissue disorders         
Acne * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Hyperhidrosis * 1  0/31 (0.00%)  2/35 (5.71%)  0/22 (0.00%)  0/27 (0.00%) 
Rash * 1  3/31 (9.68%)  1/35 (2.86%)  1/22 (4.55%)  0/27 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA Version 18.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Senior Medical Director
Organization: Janssen Research & Development, LLC
Phone: 844-434-4210
EMail: ClinicalTrialDisclosure@its.jnj.com
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT02133001     History of Changes
Other Study ID Numbers: CR103162
ESKETINSUI2001 ( Other Identifier: Janssen Research & Development, LLC )
First Submitted: May 6, 2014
First Posted: May 7, 2014
Results First Submitted: April 2, 2019
Results First Posted: April 24, 2019
Last Update Posted: April 24, 2019