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A Study to Evaluate the Efficacy, Safety, and Tolerability of Fixed Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression (TRANSFORM-1)

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ClinicalTrials.gov Identifier: NCT02417064
Recruitment Status : Completed
First Posted : April 15, 2015
Results First Posted : April 18, 2019
Last Update Posted : April 18, 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 Treatment-resistant Depression
Interventions Drug: Esketamine
Drug: Placebo
Drug: Duloxetine (Oral Antidepressant)
Drug: Escitalopram (Oral antidepressant)
Drug: Sertraline (Oral Antidepressant)
Drug: Venlafaxine Extended Release (XR) (Oral Antidepressant)
Enrollment 346
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Period Title: Double-blind Induction Phase (4 Weeks)
Started 117 116 113
Full Analysis Set (FAS) 115 114 113
Safety Analysis Set 115 116 113
Completed 111 97 107
Not Completed 6 19 6
Reason Not Completed
Adverse Event             1             7             2
Lack of Efficacy             1             1             0
Lost to Follow-up             0             1             0
Protocol Violation             2             1             1
Withdrawal by Subject             1             5             1
Other             1             4             2
Period Title: Follow-up Phase (24 Weeks)
Started 47 52 69
Completed 8 10 18
Not Completed 39 42 51
Reason Not Completed
Lost to Follow-up             0             2             1
Protocol Violation             0             0             1
Withdrawal by Subject             3             9             2
PI Decision             34             29             44
Other             2             2             3
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo Total
Hide Arm/Group Description Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Total of all reporting groups
Overall Number of Baseline Participants 115 116 113 344
Hide Baseline Analysis Population Description
The safety analysis set included all randomized participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant medication during the double-blind induction phase.
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
<=18 years
0
   0.0%
1
   0.9%
1
   0.9%
2
   0.6%
Between 18 and 65 years
115
 100.0%
115
  99.1%
112
  99.1%
342
  99.4%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 116 participants 113 participants 344 participants
46.4  (11.18) 45.7  (11.02) 46.8  (11.36) 46.3  (11.16)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
Female
81
  70.4%
80
  69.0%
81
  71.7%
242
  70.3%
Male
34
  29.6%
36
  31.0%
32
  28.3%
102
  29.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
Hispanic or Latino
33
  28.7%
27
  23.3%
31
  27.4%
91
  26.5%
Not Hispanic or Latino
74
  64.3%
80
  69.0%
71
  62.8%
225
  65.4%
Unknown or Not Reported
8
   7.0%
9
   7.8%
11
   9.7%
28
   8.1%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
American Indian or Alaska Native
0
   0.0%
1
   0.9%
0
   0.0%
1
   0.3%
Asian
2
   1.7%
1
   0.9%
2
   1.8%
5
   1.5%
Black or African American
7
   6.1%
8
   6.9%
5
   4.4%
20
   5.8%
White
91
  79.1%
86
  74.1%
86
  76.1%
263
  76.5%
More than one race
8
   7.0%
11
   9.5%
11
   9.7%
30
   8.7%
Unknown or Not Reported
7
   6.1%
9
   7.8%
9
   8.0%
25
   7.3%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 116 participants 113 participants 344 participants
Belgium
8
   7.0%
9
   7.8%
12
  10.6%
29
   8.4%
Brazil
20
  17.4%
19
  16.4%
18
  15.9%
57
  16.6%
Canada
7
   6.1%
7
   6.0%
6
   5.3%
20
   5.8%
Estonia
3
   2.6%
4
   3.4%
3
   2.7%
10
   2.9%
France
11
   9.6%
10
   8.6%
10
   8.8%
31
   9.0%
Hungary
3
   2.6%
2
   1.7%
1
   0.9%
6
   1.7%
Mexico
14
  12.2%
16
  13.8%
15
  13.3%
45
  13.1%
Slovakia
4
   3.5%
3
   2.6%
3
   2.7%
10
   2.9%
United States
45
  39.1%
46
  39.7%
45
  39.8%
136
  39.5%
1.Primary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28 of Double- Blind Induction Phase- Mixed- Effects Model Using Repeated Measures (MMRM) Analysis
Hide Description MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Time Frame Baseline up to Day 28 of Double-blind Induction Phase
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 111 98 108
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-19.0  (13.86) -18.8  (14.12) -14.8  (15.07)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine 84 mg Plus Oral AD, Oral AD Plus Intranasal Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.088
Comments [Not Specified]
Method Mixed Model for Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square (LS) Means
Estimated Value -3.2
Confidence Interval (2-Sided) 95%
-6.88 to 0.45
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine 56 mg Plus Oral Antidepressant, Oral AD Plus Intranasal Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square (LS) Means
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-7.67 to -0.49
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis
Hide Description MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using Last Observation Carried Forward (LOCF) method and last post baseline observation during double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Double-blind Endpoint (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (FAS): all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral antidepressant medication during double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 115 113 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-18.3  (14.21) -17.4  (14.25) -14.3  (15.00)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine 84 mg Plus Oral AD, Oral AD Plus Intranasal Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value = 0.250
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square (LS) Means
Estimated Value -2.0
Confidence Interval (2-Sided) 95%
-5.52 to 1.42
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine 56 mg Plus Oral Antidepressant, Oral AD Plus Intranasal Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square (LS) Means
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-7.53 to -0.6
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Onset of Clinical Response by Day 2 and Day 8
Hide Description A participant was defined as having a clinical response if there was at least 50% improvement (decrease) from baseline in the MADRS total score with onset by Day 2 and Day 8 that was maintained to Day 28. Participants were allowed one excursion (non-response) on Days 8, 15 or 22, however score must show at least 25% improvement. Participants who did not meet these criteria or discontinued during the study before Day 28 were considered as non-responders and were assigned the value of 0 (that is no). MADRS is clinician-rated scale that consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), for total possible score of 0 to 60. Higher scores represent more severe condition.
Time Frame Day 2 up to Day 28 and Day 8 up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 115 114 113
Measure Type: Number
Unit of Measure: Percentage of Participants
Day 2 up to Day 28 10.4 8.8 1.8
Day 8 up to Day 28 13.0 11.4 3.5
4.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis
Hide Description The SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1) work/school, 2) social life, and 3) family life/home responsibilities using 0 (not at all) to 10 (extremely) rating scale. Score for first 3 items are summed to create total score of 0 (unimpaired) to 30 (highly impaired), where higher score indicates greater impairment.
Time Frame Baseline up to Day 28 of Double-blind Induction phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 88 87 90
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-11.0  (9.32) -11.1  (10.04) -8.4  (9.70)
5.Secondary Outcome
Title Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis
Hide Description The SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1) work/school, 2) social life, and 3) family life/home responsibilities using 0 (not at all) to 10 (extremely) rating scale. Score for first 3 items are summed to create total score of 0 (unimpaired) to 30 (highly impaired) where higher score indicates greater impairment. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Double-blind Endpoint (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 91 99 95
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-10.7  (9.39) -10.2  (10.00) -8.1  (9.57)
6.Secondary Outcome
Title Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis
Hide Description PHQ-9 is 9-item, self-reported scale assessing 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria. Each item is rated on 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half days, 3 = Nearly every day). The scores are summed for a total score ranging from 0-27. Higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19), Severe (20-27). The recall period is 2 weeks.
Time Frame Baseline up to Day 28 of Double-blind Induction phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 110 99 108
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-11.0  (8.07) -11.7  (7.74) -9.1  (8.35)
7.Secondary Outcome
Title Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis
Hide Description PHQ-9 is 9-item, self-reported scale assessing 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria. Each item is rated on 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half days, 3 = Nearly every day). The scores are summed for a total score ranging from 0-27. Higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19), Severe (20-27). The recall period is 2 weeks. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Double-blind Endpoint (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 113 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-10.9  (8.26) -10.9  (7.81) -8.9  (8.37)
8.Secondary Outcome
Title Percentage of Participants Who Achieved at Least 50% Reduction From Baseline in MADRS Total Score at Day 28 of Double-blind Induction Phase (Observed Data)
Hide Description A participant was defined as a responder (yes=1 and no=0) at a given time point if the percent reduction from baseline in MADRS total score is at least 50 percent (%). The percentage of participants who achieved at least 50% reduction from baseline were reported. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Time Frame At Day 28 of Double-blind Induction phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 111 98 108
Measure Type: Number
Unit of Measure: Percentage of Participants
54.1 53.1 38.9
9.Secondary Outcome
Title Percentage of Participants Who Achieved at Least 50% Reduction From Baseline in MADRS Total Score at the Endpoint (Double-blind Induction Phase [Day 28]) (LOCF Data)
Hide Description A participant was defined as a responder (yes=1 and no=0) at a given time point if the percent reduction from baseline in MADRS total score is at least 50 percent (%). The percentage of participants who achieved at least 50% reduction from baseline were reported. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame At Day 28 (Double-blind Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 115 113 113
Measure Type: Number
Unit of Measure: Percentage of Participants
53.0 47.8 37.2
10.Secondary Outcome
Title Percentage of Participants in Remission (MADRS<=12) at Day 28 of Double-blind Induction Phase (Observed Data)
Hide Description Participants who had a MADRS total score of less than or equal to (<=) 12 were considered as remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Time Frame At Day 28 of Double-blind Induction Phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 111 98 108
Measure Type: Number
Unit of Measure: Percentage of participants
36 38.8 30.6
11.Secondary Outcome
Title Percentage of Participants in Remission (MADRS<=12) at the Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis (LOCF Data)
Hide Description Participants who had a MADRS total score of less than or equal to (<=) 12 were considered as remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame At Day 28 (Double-blind Endpoint)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 115 113 113
Measure Type: Number
Unit of Measure: Percentage of participants
34.8 35.4 29.2
12.Secondary Outcome
Title Change From Baseline in Clinical Global Impression - Severity (CGI-S) Score up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Description CGI-S provides measure of severity of participant’s illness including participant’s history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients (a decrease in score indicates improvement). Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Double-blind Endpoint (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 115 113 113
Median (Full Range)
Unit of Measure: Units on a scale
-2.0
(-5 to 1)
-2.0
(-5 to 1)
-1.0
(-6 to 3)
13.Secondary Outcome
Title Change From Baseline in Generalized Anxiety Disorder-7 Item (GAD-7) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Description GAD-7 is a brief and validated 7-item self-reported assessment of overall anxiety. Participants responded to each item using a 4 point scale with response categories of 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield a total score with a range of 0 to 21, where higher scores indicate more anxiety. The recall period is 2 weeks. The severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14) and Severe (15-21). Missing data was imputed using LOCF method and the last post baseline observation during the double-blind induction phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Double-blind Endpoint (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 111 109 111
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-7.4  (5.94) -7.7  (5.72) -6.0  (6.01)
14.Secondary Outcome
Title Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): Health Status Index
Hide Description EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). The descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each has 5 levels (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses are used to generate Health Status Index (HSI). HSI range is -0.148 to 0.949, is anchored at 0 (dead) and 1 (full health).
Time Frame Baseline up to End of Double-blind Induction Phase (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 113 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
0.224  (0.2481) 0.243  (0.2395) 0.181  (0.2495)
15.Secondary Outcome
Title Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): EQ-VAS
Hide Description EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-VAS self-rating records the respondent’s own assessment of his/her overall health status at time of completion, on scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine).
Time Frame Baseline up to end of Double-blind induction phase (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 113 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
20.9  (25.04) 19.1  (26.86) 14.9  (27.15)
16.Secondary Outcome
Title Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) up to End of Double-blind Induction Phase (Day 28): Sum Score
Hide Description EQ-5D-5L measures health outcome self-completed by respondents. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). The descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort, anxiety/depression. Each has 5 levels (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). The responses are used to generate Health Status Index (HSI). HSI range is -0.148 to 0.949, is anchored at 0 (dead) and 1 (full health). EQ-VAS self-rating records the respondent’s own assessment of his/her overall health status at time of completion, on scale of 0 (the worst health you can imagine) to 100 (the best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) *5. Higher score indicates worst health state.
Time Frame Baseline up to end of Double-blind Induction phase (Day 28)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS: all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during the double-blind induction phase. Here 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine 56 mg Plus Oral Antidepressant Intranasal Esketamine 84 mg Plus Oral AD Oral AD Plus Intranasal Placebo
Hide Arm/Group Description:
Participants self-administered 56 milligram (mg) of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine extended release (XR) (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered intranasal matching placebo, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Overall Number of Participants Analyzed 113 112 113
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-19.0  (18.84) -19.4  (18.43) -14.6  (19.78)
Time Frame Up to follow up phase (Week 24)
Adverse Event Reporting Description The population analyzed included safety analysis set- all randomized participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant medication during double-blind induction phase and follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.
 
Arm/Group Title DB Phase: Intranasal Esk 56 mg + Oral AD DB Phase: Intranasal Esk 84 mg + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk 56 mg + Oral AD FU Phase: Intranasal Esk 84 mg + Oral AD FU Phase: Oral AD + Intranasal Placebo
Hide Arm/Group Description Participants self-administered 56 mg of intranasal esketamine (Esk) twice per week for 4 weeks in double-blind (DB) induction phase. Also, participants simultaneously initiated new oral antidepressant (AD) with one of following: duloxetine (60 [milligram] mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants self-administered 56 mg of intranasal esketamine on Day 1 and then 84 mg from Day 4 onwards twice per week for 4 Weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants self-administered intranasal matching placebo, intranasally, twice per week for 4 weeks in DB induction phase. Also, participants simultaneously initiated new oral AD with one of following: duloxetine (60 mg/day- Weeks 1, 2, 3 and 4), escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2 to 4 with minimum therapeutic dose [MTD] of 10 mg/day), sertraline (50 mg/day- Week 1, 100 mg/day- Week 2, 150 mg/day- Week 3 and 200 mg/day- Week 4 with MTD of 50 mg/day) or venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, 225 mg/day- Weeks 3 and 4 with MTD of 150 mg/day) on Day 1 taken daily in DB induction phase. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 56 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up (FU) phase for up to 24 weeks to assess safety and tolerability including withdrawal symptoms of study drug and for collection of additional informative data to assess the course of the participant’s major depressive episode over a 24-week period. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal Esk 84 mg+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks to assess safety and tolerability including withdrawal symptoms of study drug and for collection of additional informative data to assess the course of the participant’s major depressive episode over a 24-week period. Participants who were not eligible or chose to not participate in maintenance of effect study (ESKETINTRD3003) and had received at least 1 dose of intranasal placebo+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks to assess safety and tolerability including withdrawal symptoms of study drug and for collection of additional informative data to assess the course of the participant’s major depressive episode over a 24-week period.
All-Cause Mortality
DB Phase: Intranasal Esk 56 mg + Oral AD DB Phase: Intranasal Esk 84 mg + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk 56 mg + Oral AD FU Phase: Intranasal Esk 84 mg + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/115 (0.00%)   0/116 (0.00%)   0/113 (0.00%)   0/47 (0.00%)   0/52 (0.00%)   0/69 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
DB Phase: Intranasal Esk 56 mg + Oral AD DB Phase: Intranasal Esk 84 mg + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk 56 mg + Oral AD FU Phase: Intranasal Esk 84 mg + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/115 (1.74%)   0/116 (0.00%)   0/113 (0.00%)   2/47 (4.26%)   2/52 (3.85%)   1/69 (1.45%) 
Nervous system disorders             
Headache * 1  1/115 (0.87%)  0/116 (0.00%)  0/113 (0.00%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Psychiatric disorders             
Anxiety * 1  0/115 (0.00%)  0/116 (0.00%)  0/113 (0.00%)  0/47 (0.00%)  1/52 (1.92%)  0/69 (0.00%) 
Depression * 1  1/115 (0.87%)  0/116 (0.00%)  0/113 (0.00%)  2/47 (4.26%)  1/52 (1.92%)  0/69 (0.00%) 
Insomnia * 1  0/115 (0.00%)  0/116 (0.00%)  0/113 (0.00%)  0/47 (0.00%)  1/52 (1.92%)  0/69 (0.00%) 
Suicidal Ideation * 1  0/115 (0.00%)  0/116 (0.00%)  0/113 (0.00%)  0/47 (0.00%)  0/52 (0.00%)  1/69 (1.45%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
DB Phase: Intranasal Esk 56 mg + Oral AD DB Phase: Intranasal Esk 84 mg + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk 56 mg + Oral AD FU Phase: Intranasal Esk 84 mg + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   93/115 (80.87%)   92/116 (79.31%)   64/113 (56.64%)   7/47 (14.89%)   4/52 (7.69%)   7/69 (10.14%) 
Ear and labyrinth disorders             
Vertigo * 1  24/115 (20.87%)  24/116 (20.69%)  2/113 (1.77%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Eye disorders             
Vision Blurred * 1  8/115 (6.96%)  9/116 (7.76%)  0/113 (0.00%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Gastrointestinal disorders             
Diarrhoea * 1  8/115 (6.96%)  5/116 (4.31%)  3/113 (2.65%)  0/47 (0.00%)  1/52 (1.92%)  2/69 (2.90%) 
Hypoaesthesia Oral * 1  16/115 (13.91%)  12/116 (10.34%)  2/113 (1.77%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Nausea * 1  31/115 (26.96%)  37/116 (31.90%)  12/113 (10.62%)  2/47 (4.26%)  1/52 (1.92%)  1/69 (1.45%) 
Paraesthesia Oral * 1  9/115 (7.83%)  1/116 (0.86%)  2/113 (1.77%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Vomiting * 1  7/115 (6.09%)  14/116 (12.07%)  2/113 (1.77%)  1/47 (2.13%)  0/52 (0.00%)  0/69 (0.00%) 
General disorders             
Fatigue * 1  12/115 (10.43%)  8/116 (6.90%)  5/113 (4.42%)  0/47 (0.00%)  0/52 (0.00%)  1/69 (1.45%) 
Feeling Drunk * 1  7/115 (6.09%)  3/116 (2.59%)  0/113 (0.00%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Investigations             
Blood Pressure Increased * 1  8/115 (6.96%)  11/116 (9.48%)  5/113 (4.42%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Nervous system disorders             
Dizziness * 1  32/115 (27.83%)  26/116 (22.41%)  10/113 (8.85%)  0/47 (0.00%)  1/52 (1.92%)  1/69 (1.45%) 
Dizziness Postural * 1  7/115 (6.09%)  7/116 (6.03%)  0/113 (0.00%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Dysgeusia * 1  17/115 (14.78%)  20/116 (17.24%)  17/113 (15.04%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Headache * 1  23/115 (20.00%)  24/116 (20.69%)  19/113 (16.81%)  4/47 (8.51%)  2/52 (3.85%)  3/69 (4.35%) 
Hypoaesthesia * 1  14/115 (12.17%)  16/116 (13.79%)  2/113 (1.77%)  0/47 (0.00%)  1/52 (1.92%)  0/69 (0.00%) 
Lethargy * 1  7/115 (6.09%)  5/116 (4.31%)  1/113 (0.88%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Mental Impairment * 1  6/115 (5.22%)  3/116 (2.59%)  1/113 (0.88%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Paraesthesia * 1  19/115 (16.52%)  11/116 (9.48%)  3/113 (2.65%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Sedation * 1  6/115 (5.22%)  8/116 (6.90%)  1/113 (0.88%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Somnolence * 1  24/115 (20.87%)  21/116 (18.10%)  13/113 (11.50%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Tremor * 1  4/115 (3.48%)  6/116 (5.17%)  2/113 (1.77%)  1/47 (2.13%)  0/52 (0.00%)  1/69 (1.45%) 
Psychiatric disorders             
Anxiety * 1  10/115 (8.70%)  9/116 (7.76%)  7/113 (6.19%)  1/47 (2.13%)  0/52 (0.00%)  2/69 (2.90%) 
Dissociation * 1  30/115 (26.09%)  32/116 (27.59%)  4/113 (3.54%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Euphoric Mood * 1  8/115 (6.96%)  2/116 (1.72%)  2/113 (1.77%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Insomnia * 1  10/115 (8.70%)  8/116 (6.90%)  11/113 (9.73%)  0/47 (0.00%)  1/52 (1.92%)  0/69 (0.00%) 
Renal and urinary disorders             
Pollakiuria * 1  6/115 (5.22%)  2/116 (1.72%)  1/113 (0.88%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Nasal Discomfort * 1  4/115 (3.48%)  5/116 (4.31%)  7/113 (6.19%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
Throat Irritation * 1  5/115 (4.35%)  9/116 (7.76%)  4/113 (3.54%)  0/47 (0.00%)  0/52 (0.00%)  0/69 (0.00%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
Transient, dissociative effects of esketamine are difficult to blind, site staff who observed treatment sessions could have been biased. To ensure unbiased efficacy evaluations, independent, remote, blinded MADRS raters assessed treatment response.
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 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: NCT02417064     History of Changes
Other Study ID Numbers: CR107146
ESKETINTRD3001 ( Other Identifier: Janssen Research & Development, LLC )
2014-004584-20 ( EudraCT Number )
First Submitted: April 10, 2015
First Posted: April 15, 2015
Results First Submitted: March 28, 2019
Results First Posted: April 18, 2019
Last Update Posted: April 18, 2019