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Trial record 79 of 125 for:    "Depressive Disorder" [DISEASE] AND Behavioral | ( Map: Spain )

A Study to Evaluate the Efficacy, Safety, and Tolerability of Flexible Doses of Intranasal Esketamine Plus an Oral Antidepressant in Adult Participants With Treatment-resistant Depression (TRANSFORM-2)

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ClinicalTrials.gov Identifier: NCT02418585
Recruitment Status : Completed
First Posted : April 16, 2015
Results First Posted : April 19, 2019
Last Update Posted : April 29, 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 236
Recruitment Details  
Pre-assignment Details Total 236 participants were enrolled, out of which 227 were randomized and 9 participants were excluded due to Good Clinical Practice (GCP) violations.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 (DB) Phase (4 Weeks)
Started 116 111
Safety Analysis Set 115 109
Full Analysis Set 114 109
Completed 98 99
Not Completed 18 12
Reason Not Completed
Lost to Follow-up             1             1
Protocol Violation             2             2
Withdrawal by Subject             4             7
Lack of Efficacy             2             0
Adverse Event             9             1
Other             0             1
Period Title: Follow-up Phase (24 Weeks)
Started 34 52
Completed 16 27
Not Completed 18 25
Reason Not Completed
Lost to Follow-up             3             3
Withdrawal by Subject             6             3
Investigator Decision             6             17
Other             3             2
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD Total
Hide Arm/Group Description Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks. Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 115 109 224
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 109 participants 224 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
115
 100.0%
109
 100.0%
224
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 115 participants 109 participants 224 participants
45  (12.56) 46.4  (11.14) 45.7  (11.89)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 109 participants 224 participants
Female
76
  66.1%
63
  57.8%
139
  62.1%
Male
39
  33.9%
46
  42.2%
85
  37.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 109 participants 224 participants
Hispanic or Latino
5
   4.3%
7
   6.4%
12
   5.4%
Not Hispanic or Latino
109
  94.8%
99
  90.8%
208
  92.9%
Unknown or Not Reported
1
   0.9%
3
   2.8%
4
   1.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 109 participants 224 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
1
   0.9%
1
   0.9%
2
   0.9%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
6
   5.2%
5
   4.6%
11
   4.9%
White
107
  93.0%
102
  93.6%
209
  93.3%
More than one race
1
   0.9%
1
   0.9%
2
   0.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 115 participants 109 participants 224 participants
CZECH REPUBLIC
30
  26.1%
28
  25.7%
58
  25.9%
GERMANY
10
   8.7%
10
   9.2%
20
   8.9%
POLAND
20
  17.4%
18
  16.5%
38
  17.0%
SPAIN
9
   7.8%
9
   8.3%
18
   8.0%
UNITED STATES
46
  40.0%
44
  40.4%
90
  40.2%
1.Primary Outcome
Title Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28 in the 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) defined as all randomized participants who received at least 1 dose of intranasal study medication, 1 dose of oral antidepressant (AD) medication during double-blind induction phase (D-BIP). Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 101 100
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-21.4  (12.32) -17.0  (13.88)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD), Intranasal Placebo Plus Oral AD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.020
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 -4.0
Confidence Interval (2-Sided) 95%
-7.31 to -0.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.69
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])- Analysis of Covariance (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. The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS defined as all randomized participants who received at least 1 dose of intranasal study medication, 1 dose of AD medication during double-blind induction phase (D-BIP). Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 112 109
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-19.6  (13.58) -16.3  (14.24)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD), Intranasal Placebo Plus Oral AD
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value =0.034
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference of Least Square (LS) Means
Estimated Value -3.5
Confidence Interval (2-Sided) 95%
-6.67 to -0.26
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Onset of Clinical Response on Day 2 and Day 8
Hide Description A participant was defined as having a clinical response if there is at least 50 percent (%) improvement from baseline in the MADRS total score with onset by Day 2 and Day 8 that was maintained to Day 28. 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. Participants who did not meet such criterion or discontinue during the study before Day 28 for any reason were considered as non-responders.
Time Frame Day 2 up to Day 28 and Day 8 up to Day 28
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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 (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 114 109
Measure Type: Number
Unit of Measure: Percentage of participants
Onset of Clinical response on Day 2 7.9 4.6
Onset of Clinical response on Day 8 10.5 6.4
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. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive.
Time Frame Baseline up to Day 28 of Double-blind Induction phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during double-blind induction phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 86 85
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-13.6  (8.31) -9.4  (8.43)
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. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive. The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during double-blind induction phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 95 89
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-12.5  (8.85) -9.3  (8.39)
6.Secondary Outcome
Title Change From Baseline in Patient Health Questionnaire – 9-Item Depression Module (PHQ-9) Total Score up to Day 28 of Double-blind Induction Phase- MMRM Analysis
Hide Description PHQ-9 is 9-item, self-report scale assessing depressive symptoms. Each item is rated on 4-point scale (0=Not at all, 1=Several Days, 2=More than half days, 3=Nearly every day. Scale scores each of 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria and it has been used both as screening tool and measure of response to treatment for depression. The participant’s item responses are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. Severity of PHQ-9 categorized as follows: None-minimal (0-4), Mild (5-9), Moderate (10-14), Moderately Severe (15-19), Severe (20-27).
Time Frame Baseline up to Day 28 of Double-blind Induction phase
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during double-blind induction phase. Here 'N' signifies overall number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 104 100
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-13.0  (6.42) -10.2  (7.80)
7.Secondary Outcome
Title Change From Baseline in Patient Health Questionnaire – 9-Item Depression Module (PHQ-9) Total Score up to Endpoint (Double-blind Induction Phase [Day 28])- ANCOVA Analysis
Hide Description PHQ-9 is 9-item, self-report scale assessing depressive symptoms. Each item is rated on 4-point scale (0=Not at all, 1=Several Days, 2=More than half days, 3=Nearly every day). Scale scores each of 9 symptom domains of Diagnostic and Statistical Manual of Mental Disorders, Major Depressive Disorder criteria and it has been used both as screening tool and measure of response to treatment for depression. The participant’s item responses are summed to provide a total score (range of 0 to 27) with higher scores indicating greater severity of depressive symptoms. 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 last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as all randomized participants who received at least 1 dose of intranasal study medication and 1 dose of oral AD medication during double-blind induction phase. Here 'N' signifies overall number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 111 105
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-12.2  (6.87) -10.1  (7.87)
8.Secondary Outcome
Title Percentage of Participants Who Achieved >=50% Reduction From Baseline in MADRS Total Score at the Endpoint (Double-blind Induction Phase [Day 28])
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. The percentage of participants with greater than or equal to (>=) 50 % reduction from baseline in MADRS total score was reported. The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame At Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 112 109
Measure Type: Number
Unit of Measure: Percentage of participants
63.4 49.5
9.Secondary Outcome
Title Percentage of Participants in Remission (MADRS<=12) at the Endpoint (Double-blind Induction Phase [Day 28])
Hide Description Remission was defined as participants who had a MADRS total score of less than or equal to (=<) 12. 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. The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame At Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 112 109
Measure Type: Number
Unit of Measure: Percentage of participants
48.2 30.3
10.Secondary Outcome
Title Percentage of Participants in Response (SDS Total Score <=12 and Individual Item Scores Each <=4) at the End of 4-Week Double-blind Induction Phase (Day 28)
Hide Description Response defined as SDS total score <= 12 and individual item scores each <= 4. SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive.
Time Frame At Day 28 [end of Double-blind Induction Phase]
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 86 86
Measure Type: Number
Unit of Measure: Percentage of participants
57.0 39.5
11.Secondary Outcome
Title Percentage of Participants in Remission (SDS Total Score <=6 and Individual Item Scores Each <=2) at the End of 4-Week Double-blind Induction Phase (Day 28)
Hide Description Remission defined as SDS total score <= 6 and individual item scores each <= 2. SDS is a participant reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items were summed to create a total score of 0-30 where a higher score indicates greater impairment. It also has one item on days lost from school or work and one item on days when under productive.
Time Frame At Day 28 (End of Double-blind Induction Phase)
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 86 86
Measure Type: Number
Unit of Measure: Percentage of participants
39.5 20.9
12.Secondary Outcome
Title Change From Baseline in Clinical Global Impression-Severity (CGI-S) Total 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. CGI-S permits global evaluation of participant’s condition at given time. The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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
Median (Full Range)
Unit of Measure: Units on a scale
-2.0
(-5 to 1)
-2.0
(-5 to 1)
13.Secondary Outcome
Title Change From Baseline in Generalized Anxiety Disorder (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-report assessment of overall anxiety. Participants respond 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). The last post baseline observation during the phase was carried forward as “End Point” for that phase.
Time Frame Baseline up to Endpoint (Double-blind Induction Phase [Day 28])
Hide Outcome Measure Data
Hide Analysis Population Description
FAS is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 110 102
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-7.9  (6.12) -6.8  (5.75)
14.Secondary Outcome
Title Change From Baseline in EQ 5D-5L-Health Status Index to End of Double-blind Induction Phase (Day 28)
Hide Description European Quality of Life Group-5 Dimension-5-Level (EQ-5D-5L) is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health “today”. Responses were used to generate a Health Status Index (HSI). Health Status Index range is -0.148 - 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 is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 111 105
Mean (Standard Deviation)
Unit of Measure: Units on a Scale
0.288  (0.2317) 0.231  (0.2506)
15.Secondary Outcome
Title Change From Baseline in EQ 5D-5L- European Quality of Life – Visual Analogue Scale (EQ-VAS) to End of Double-blind Induction Phase (Day 28)
Hide Description EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent’s own assessment of his or her overall health status at the time of completion, on a 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 is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 111 105
Mean (Standard Deviation)
Unit of Measure: Units on a scale
29.1  (26.32) 20.9  (26.60)
16.Secondary Outcome
Title Change From Baseline in EQ 5D-5L- Sum Score to End of Double-blind Induction Phase (Day 28)
Hide Description EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ VAS). EQ-5D-5L descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each has 5 levels of perceived problems (1-no problem, 2-slight problems, 3-moderate problems, 4-severe problems, 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health “today”. Responses were used to generate a Health Status Index (HSI). Health Status Index range is -0.148 - 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 a scale of 0 (worst health you can imagine) to 100 (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 is defined as 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' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.
Arm/Group Title Intranasal Esketamine (Esk) Plus Oral Antidepressant (AD) Intranasal Placebo Plus Oral AD
Hide Arm/Group Description:
Participants self-administered (under direct supervision by HCP) esketamine 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22,25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day-Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day-Week 1, 150 mg/day-Week 2, and 225 mg/day-Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003[NCT02493868]) and had received at least 1 dose of intranasal Esketamine+ Oral AD in DB induction phase were followed in posttreatment follow-up phase for up to 24 weeks.
Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1,4,8,11,15,18,22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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 111 105
Mean (Standard Deviation)
Unit of Measure: Units on a scale
-23.2  (16.64) -17.1  (19.66)
Time Frame Approximately up to 2.2 Years
Adverse Event Reporting 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. The follow-up analysis set included all participants who entered the follow-up phase.
 
Arm/Group Title DB Phase: Intranasal Esk + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk + Oral AD FU Phase: Oral AD + Intranasal Placebo
Hide Arm/Group Description Participants self-administered (under direct supervision by health care professional [HCP]) esketamine either 56 milligram (mg) or 84 mg intranasally twice weekly for 4 weeks (on Day 1, 4, 8, 11, 15, 18, 22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral antidepressant (AD) with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants self-administered (under direct supervision by HCP) esketamine matched placebo intranasally twice weekly for 4 weeks (on Day 1, 4, 8, 11, 15, 18, 22 and 25). Simultaneously, participants initiated per fixed titration scheme a new open-label oral AD with one of following: [Duloxetine (60 milligram (mg)/day- Weeks 1-4 with minimum dose for tolerability [MDT] of 60 mg/day); Escitalopram (10 mg/day- Week 1 and 20 mg/day- Weeks 2-4 with MDT 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 MDT of 50 mg/day) or Venlafaxine XR (75 mg/day- Week 1, 150 mg/day- Week 2, and 225 mg/day- Weeks 3 and 4 with MDT of 150 mg/day) during DB Induction Phase. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) and had received at least 1 dose of intranasal Esk+ Oral AD in DB induction phase were followed in posttreatment follow-up (FU) phase for up to 24 weeks. Participants who were not eligible or who chose to not participate in maintenance of effect study (ESKETINTRD3003 [NCT02493868]) 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.
All-Cause Mortality
DB Phase: Intranasal Esk + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/115 (0.87%)   0/109 (0.00%)   0/34 (0.00%)   0/52 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
DB Phase: Intranasal Esk + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/115 (0.87%)   1/109 (0.92%)   1/34 (2.94%)   0/52 (0.00%) 
Ear and labyrinth disorders         
Vertigo Positional * 1  0/115 (0.00%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Injury, poisoning and procedural complications         
Multiple Injuries * 1  1/115 (0.87%)  0/109 (0.00%)  0/34 (0.00%)  0/52 (0.00%) 
Road Traffic Accident * 1  1/115 (0.87%)  0/109 (0.00%)  0/34 (0.00%)  0/52 (0.00%) 
Nervous system disorders         
Cerebral Haemorrhage * 1  0/115 (0.00%)  0/109 (0.00%)  1/34 (2.94%)  0/52 (0.00%) 
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 + Oral AD DB Phase: Oral AD + Intranasal Placebo FU Phase: Intranasal Esk + Oral AD FU Phase: Oral AD + Intranasal Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   90/115 (78.26%)   53/109 (48.62%)   7/34 (20.59%)   6/52 (11.54%) 
Ear and labyrinth disorders         
Vertigo * 1  30/115 (26.09%)  3/109 (2.75%)  0/34 (0.00%)  0/52 (0.00%) 
Eye disorders         
Vision Blurred * 1  14/115 (12.17%)  3/109 (2.75%)  0/34 (0.00%)  0/52 (0.00%) 
Gastrointestinal disorders         
Diarrhoea * 1  10/115 (8.70%)  10/109 (9.17%)  1/34 (2.94%)  2/52 (3.85%) 
Dry Mouth * 1  9/115 (7.83%)  3/109 (2.75%)  1/34 (2.94%)  0/52 (0.00%) 
Hypoaesthesia Oral * 1  9/115 (7.83%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Nausea * 1  30/115 (26.09%)  7/109 (6.42%)  1/34 (2.94%)  0/52 (0.00%) 
Paraesthesia Oral * 1  9/115 (7.83%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Vomiting * 1  11/115 (9.57%)  2/109 (1.83%)  0/34 (0.00%)  0/52 (0.00%) 
General disorders         
Fatigue * 1  5/115 (4.35%)  6/109 (5.50%)  0/34 (0.00%)  0/52 (0.00%) 
Feeling Drunk * 1  9/115 (7.83%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Infections and infestations         
Upper Respiratory Tract Infection * 1  0/115 (0.00%)  1/109 (0.92%)  3/34 (8.82%)  0/52 (0.00%) 
Investigations         
Blood Pressure Increased * 1  11/115 (9.57%)  0/109 (0.00%)  0/34 (0.00%)  0/52 (0.00%) 
Metabolism and nutrition disorders         
Decreased Appetite * 1  2/115 (1.74%)  3/109 (2.75%)  2/34 (5.88%)  0/52 (0.00%) 
Nervous system disorders         
Dizziness * 1  24/115 (20.87%)  5/109 (4.59%)  1/34 (2.94%)  2/52 (3.85%) 
Dizziness Postural * 1  8/115 (6.96%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Dysgeusia * 1  28/115 (24.35%)  13/109 (11.93%)  0/34 (0.00%)  0/52 (0.00%) 
Headache * 1  23/115 (20.00%)  19/109 (17.43%)  2/34 (5.88%)  1/52 (1.92%) 
Hypoaesthesia * 1  8/115 (6.96%)  1/109 (0.92%)  0/34 (0.00%)  0/52 (0.00%) 
Paraesthesia * 1  13/115 (11.30%)  1/109 (0.92%)  1/34 (2.94%)  0/52 (0.00%) 
Somnolence * 1  15/115 (13.04%)  7/109 (6.42%)  0/34 (0.00%)  0/52 (0.00%) 
Psychiatric disorders         
Anxiety * 1  12/115 (10.43%)  5/109 (4.59%)  1/34 (2.94%)  1/52 (1.92%) 
Dissociation * 1  30/115 (26.09%)  4/109 (3.67%)  0/34 (0.00%)  0/52 (0.00%) 
Insomnia * 1  11/115 (9.57%)  5/109 (4.59%)  0/34 (0.00%)  1/52 (1.92%) 
Respiratory, thoracic and mediastinal disorders         
Nasal Discomfort * 1  8/115 (6.96%)  2/109 (1.83%)  0/34 (0.00%)  0/52 (0.00%) 
Throat Irritation * 1  9/115 (7.83%)  5/109 (4.59%)  0/34 (0.00%)  0/52 (0.00%) 
1
Term from vocabulary, MedDRA Version 20.0
*
Indicates events were collected by non-systematic assessment
As this was a flexible-dose study, dose-response relationships could not be evaluated because direct comparisons between dose groups could not be made.
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: NCT02418585     History of Changes
Other Study ID Numbers: CR107147
ESKETINTRD3002 ( Other Identifier: Janssen Research & Development, LLC )
2014-004585-22 ( EudraCT Number )
First Submitted: April 13, 2015
First Posted: April 16, 2015
Results First Submitted: March 27, 2019
Results First Posted: April 19, 2019
Last Update Posted: April 29, 2019