A Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Adult Participants With Treatment-resistant Depression
Official Title
A Randomized, Double-blind, Multicenter, Active-Controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression
Acronym
SUSTAIN-1
Organization
Janssen Research & Development, LLCINDUSTRY
Status Module
Record Verification Date
Apr 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Oct 1, 2015Actual
Primary Completion Date
Feb 15, 2018Actual
Completion Date
Feb 16, 2018Actual
First Submitted Date
May 13, 2015
First Submission Date that Met QC Criteria
Jul 7, 2015
First Posted Date
Jul 10, 2015Estimated
Results Waived
Not provided
Results First Submitted Date
Mar 29, 2019
Results First Submitted that Met QC Criteria
May 20, 2019
Results First Posted Date
May 21, 2019Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Feb 12, 2019
Certification/Extension First Submitted that Passed QC Review
Feb 12, 2019
Certification/Extension First Posted Date
Feb 15, 2019Actual
Last Update Submitted Date
Apr 25, 2025
Last Update Posted Date
Apr 29, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Janssen Research & Development, LLCINDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The purpose of this study is to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms in participants with treatment-resistant depression (TRD) who are in stable remission after an induction and optimization course of intranasal esketamine plus an oral antidepressant.
Detailed Description
This is a randomized, double-blind (neither the researchers nor the participant know what treatment the participants is receiving), active-controlled, multicenter (more than 1 study site) study in participants with TRD to assess the efficacy of intranasal esketamine plus an oral antidepressant compared with an oral antidepressant (active comparator) plus intranasal placebo in delaying relapse of depressive symptoms. The study will consist of 5 phases: Screening/Prospective Observational Phase (4-7weeks) for direct-entry participants only, Open-label Induction Phase (4-weeks) for direct-entry participants only, Optimization Phase (12-weeks; open-label for direct-entry participants and double-blind for transferred-entry participants), Maintenance Phase (variable duration; double-blind for all participants) and Follow-up Phase (2-weeks). Participants' safety will be monitored throughout the study.
Conditions Module
Conditions
Depressive Disorder, Treatment-Resistant
Keywords
Treatment-resistant Depression
Esketamine
Placebo
Oral Antidepressant
Relapse prevention
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
719Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Intranasal Esketamine plus oral antidepressant
Experimental
Open-Label Induction Phase: Direct-entry participants will self-administer esketamine intranasally twice per week for 4 weeks as a flexible dose regimen in the Open-label Induction Phase. Participants will initiate a new oral antidepressant on Day 1 of this phase. Optimization Phase: Direct-entry and transferred-entry participants will self-administer intranasal esketamine (same dose) at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase. Maintenance Phase: Direct-entry and transferred-entry participants assigned to esketamine will self-administer intranasal esketamine (same dose) once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase.
Optimization Phase: Transferred-entry participants will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase. Maintenance Phase: Direct-entry and transferred-entry participants assigned to intranasal placebo will self-administer intranasal placebo once weekly or once every other week based on depressive symptoms. Participants continue same oral antidepressant treatment from induction phase.
Open-label induction phase: Direct entry participants start at a dose of 56 mg on Day 1. On Day 4, the dose may be increased to 84 mg or remain at 56 mg. From Day 8 to 22, dose may be increased to 84 mg, remain the same or be reduced to 56 mg from 84 mg per protocol, at investigator's discretion based on efficacy and/or tolerability. On Day 25, a dose reduction from 84 mg to 56 mg is permitted but no dose increase is permitted. Optimization Phase: Direct-entry and transferred-entry participants will self-administer intranasal esketamine (same dose) for first 4 weeks, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: All participants assigned to esketamine will self-administer intranasal esketamine once weekly or once every other week based on depressive symptoms.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Time to Relapse in Participants With Stable Remission (Maintenance Phase)
Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (>) 12 or one missing assessment at OP week 13 or 14.
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
Secondary Outcomes
Measure
Description
Time Frame
Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
Relapse is defined as any of following: MADRS total score >= 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable response is defined as >= 50 percent (%) reduction in MADRS total score from baseline (Day 1 of induction phase, prior to first intranasal dose) in each of the last 2 weeks of the OP phase, but without meeting criteria for stable remission.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
For Direct-Entry Participants
At the time of signing the informed consent form (ICF), participant must be a man or woman 18 (or older if the minimum legal age of consent in the country in which the study is taking place is greater than [>]18) to 64 years of age, inclusive - At the start of the screening/prospective observational phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) (if single-episode MDD, the duration must be greater than or equal to [>=] 2 years) or recurrent MDD, without psychotic features, based upon clinical assessment and confirmed by the Mini-International Neuropsychiatric Interview (MINI)
At the start of the screening/prospective observational phase, participant must have an Inventory of Depressive Symptomatology-Clinician rated ( IDS-C30) total score of greater than or equal to (>=) 34
At the start of the screening/prospective observational phase, participants must have had nonresponse (less than or equal to 25 percent [%] improvement) to greater than or equal to (>=1) but less than or equal to (<=) 5 oral antidepressant treatments taken at adequate dosage and for adequate duration, as assessed using the Massachusetts General Hospital (MGH-ATRQ )
MGH-ATRQ and documented by medical history and pharmacy/prescription records, for the current episode of depression. In addition, the participant is taking different ongoing oral antidepressant treatment (on the MGH-ATRQ) for at least the previous 2 weeks at or above the minimal therapeutic dose
The participant's current major depressive episode, depression symptom severity (Week 1 MADRS total score >=28 required), and treatment response to antidepressant treatments used in the current depressive episode (retrospectively assessed) must be deemed valid for participation in a clinical study based on a Site-Independent Qualification Assessment For Transferred-Entry Participants
The participant must have completed the double-blind induction phase in ESKETINTRD3001 or ESKETINTRD3002 and must have demonstrated response at the end of that phase (>=50% reduction in the MADRS total score from baseline [Day 1 pre-randomization] at the end of the 4-week double-blind induction phase)
Exclusion Criteria:
Participants who have previously demonstrated nonresponse of depressive symptoms to esketamine or ketamine in the current major depressive episode, to all 4 of the oral antidepressant treatment options available for the double-blind induction phase (ie, duloxetine, escitalopram, sertraline, and venlafaxine extended release [XR]) in the current major depressive episode (based on MGH-ATRQ), or an adequate course of treatment with electroconvulsive therapy (ECT) in the current major depressive episode, defined as at least 7 treatments with unilateral/bilateral ECT
Participant has received vagal nerve stimulation (VNS) or has received deep brain stimulation (DBS) in the current episode of depression
Participant has a current or prior DSM-5 diagnosis of a psychotic disorder or MDD with psychotic features, bipolar or related disorders (confirmed by the MINI), obsessive compulsive disorder (current only), intellectual disability (DSM-5 diagnostic codes 317, 318.0, 318.1, 318.2, 315.8, and 319), autism spectrum disorder, borderline personality disorder, antisocial personality disorder, histrionic personality disorder, or narcissistic personality disorder
Participant has homicidal ideation/intent, per the investigator's clinical judgment, or has suicidal ideation with some intent to act within 6 months prior to the start of the screening/prospective observational phase, per the investigator's clinical judgment or based on the Columbia Suicide Severity Rating Scale (C-SSRS)
Participants with history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
64 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Janssen Research & Development, LLC Clinical Trial
Swieczkowski D, Kwasny A, Pruc M, Szarpak L, Cubala WJ. Addressing diversity gaps in esketamine clinical trials: a registry-based cross-sectional analysis of sex, race and ethnicity. Int J Psychiatry Clin Pract. 2026 Jun;30(2):225-230. doi: 10.1080/13651501.2026.2622532. Epub 2026 Feb 12.
A Randomized, Double-blind, Multicenter, Active-controlled Study of Intranasal Esketamine Plus an Oral Antidepressant for Relapse Prevention in Treatment-resistant Depression
Out of 705 participants, 437 (direct entry [DE] participants) entered in induction (IND) phase and 268 participants (150 transferred-entry [TE] participants from study ESKETINTRD3001 [NCT02417064] and 118 participants from study ESKETINTRD3002 [NCT02418585]) entered in this study in optimization (OP) phase.
Recruitment Details
Total of 719 participants were enrolled out of which 705 were included in the analysis. 14 participants were excluded due to premature closure of a site due to quality and data integrity issues.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Periods
Title
Milestones
Reasons Not Completed
Induction Phase: DE Participants
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Apr 4, 2017
Mar 29, 2019
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Italy
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
Intranasal Esketamine plus oral antidepressant
Placebo
Drug
Optimization Phase: Transferred-entry participant will self-administer intranasal placebo at weekly treatment sessions for the first 4 weeks of this phase, then individualized to either once weekly or once every other week based on depressive symptoms. Maintenance Phase: Direct-entry and transferred-entry participants assigned to placebo will self-administer matching intranasal placebo once weekly or once based on depressive symptoms.
Placebo Plus Oral Antidepressant
Duloxetine (Oral Antidepressant)
Drug
Duloxetine could be selected as the oral antidepressant medication by the investigator based on review of Massachusetts General Hospital - Antidepressant Treatment Response Questionnaire (MGH-ATRQ) and relevant prior antidepressant medication information. The minimum therapeutic dose is 60 milligram per day (mg/day).
Intranasal Esketamine plus oral antidepressant
Placebo Plus Oral Antidepressant
Escitalopram (Oral antidepressant)
Drug
Escitalopram could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Escitalopram will be titrated upto a maximum dose of 20 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 10 mg/day.
Intranasal Esketamine plus oral antidepressant
Placebo Plus Oral Antidepressant
Sertraline (Oral Antidepressant)
Drug
Sertraline could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Sertraline will be titrated upto a maximum dose of 200 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 50 mg/day.
Venlafaxine Extended Release could be selected as the oral antidepressant medication by the investigator based on review of MGH-ATRQ and relevant prior antidepressant medication information. Venlafaxine Extended Release will be titrated upto a maximum dose of 225 mg/day, but if not tolerated the dose can be reduced to the minimum therapeutic dose of 150 mg/day.
Intranasal Esketamine plus oral antidepressant
Placebo Plus Oral Antidepressant
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (last observation carried forward [LOCF] data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). 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. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). 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. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Clinical Global Impression-Severity Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Generalized Anxiety Disorder-7 Items (GAD-7) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Generalized Anxiety Disorder-7 Items Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Sum Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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). HSI ranges from 0 (dead) to 1.00 (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.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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).
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Remission (Maintenance Phase)
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 HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EuroQol-5 Dimension-5 Level Sum Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
EQ-5D-5L 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 HSI. HSI ranges from 0 (dead) to 1.00 (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.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EQ-5D-5L EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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).
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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 HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores <= 4 for each item and <= 12 for the total score are considered response. Scores <= 2 for each item and <= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Baseline and Endpoint (Up to 92 Weeks)
Change From Baseline in Sheehan Disability Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores <= 4 for each item and <= 12 for the total score are considered response. Scores <= 2 for each item and <= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Kern Sliwa J, Naranjo RR Jr, Turkoz I, Petrillo MP, Cabrera P, Trivedi M. Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Asberg Depression Rating Scale and the 9-item Patient Health Questionnaire. CNS Spectr. 2024 Jun;29(3):176-186. doi: 10.1017/S1092852924000105. Epub 2024 Apr 1.
Castro M, Wilkinson ST, Al Jurdi RK, Petrillo MP, Zaki N, Borentain S, Fu DJ, Turkoz I, Sun L, Brown B, Cabrera P. Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study. CNS Drugs. 2023 Aug;37(8):715-723. doi: 10.1007/s40263-023-01026-3. Epub 2023 Aug 9.
Williamson DJ, Gogate JP, Kern Sliwa JK, Manera LS, Preskorn SH, Winokur A, Starr HL, Daly EJ. Longitudinal Course of Adverse Events With Esketamine Nasal Spray: A Post Hoc Analysis of Pooled Data From Phase 3 Trials in Patients With Treatment-Resistant Depression. J Clin Psychiatry. 2022 Sep 19;83(6):21m14318. doi: 10.4088/JCP.21m14318.
Chen G, Chen L, Zhang Y, Li X, Lane R, Lim P, Daly EJ, Furey ML, Fedgchin M, Popova V, Singh JB, Drevets WC. Relationship Between Dissociation and Antidepressant Effects of Esketamine Nasal Spray in Patients With Treatment-Resistant Depression. Int J Neuropsychopharmacol. 2022 Apr 19;25(4):269-279. doi: 10.1093/ijnp/pyab084.
Doty RL, Popova V, Wylie C, Fedgchin M, Daly E, Janik A, Ochs-Ross R, Lane R, Lim P, Cooper K, Melkote R, Jamieson C, Singh J, Drevets WC. Effect of Esketamine Nasal Spray on Olfactory Function and Nasal Tolerability in Patients with Treatment-Resistant Depression: Results from Four Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase III Studies. CNS Drugs. 2021 Jul;35(7):781-794. doi: 10.1007/s40263-021-00826-9. Epub 2021 Jul 7.
Daly EJ, Trivedi MH, Janik A, Li H, Zhang Y, Li X, Lane R, Lim P, Duca AR, Hough D, Thase ME, Zajecka J, Winokur A, Divacka I, Fagiolini A, Cubala WJ, Bitter I, Blier P, Shelton RC, Molero P, Manji H, Drevets WC, Singh JB. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019 Sep 1;76(9):893-903. doi: 10.1001/jamapsychiatry.2019.1189.
FG001
Oral AD + Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance (MA) phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
FG000437 subjects
FG0010 subjects
COMPLETED
FG000273 subjectsParticipants who completed and met predefined response criteria continued to OP phase.
FG000297 subjectsParticipants who completed and met predefined remission/response criteria randomized to MA phase
FG00154 subjectsParticipants who completed and met predefined remission/response criteria continued to MA phase.
NOT COMPLETED
FG000158 subjects
FG00132 subjects
Type
Comment
Reasons
Adverse Event
FG0005 subjects
FG0010 subjects
Lost to Follow-up
FG0002 subjects
FG001
Maintenance Phase: DE+TE Participants
Type
Comment
Milestone Data
STARTED
FG000152 subjects152 participants randomized from intranasal esketamine arm after OP phase: DE (90) + TE (62)
FG001199 subjects145 participants randomized from intranasal esketamine arm after OP phase+54 continued from OP phase
Stable Remitters
FG00090 subjects
FG00186 subjects
Stable Responders
FG00062 subjects
FG00159 subjects
COMPLETED
FG000139 subjects
FG001177 subjects
NOT COMPLETED
FG00013 subjects
FG00122 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0014 subjects
Lost to Follow-up
FG0001 subjects
FG001
Follow-up Phase
Type
Comment
Milestone Data
STARTED
FG000481 subjects
FG00164 subjects
COMPLETED
FG000470 subjects
FG00162 subjects
NOT COMPLETED
FG00011 subjects
FG0012 subjects
Type
Comment
Reasons
Lost to Follow-up
FG0001 subjects
FG0010 subjects
Withdrawal by Subject
FG0003 subjects
FG001
The baseline characteristics are reported for the all enrolled population. Not all participants enrolled were actually randomized to one of 2 treatments in the Maintenance phase as they had to meet specific criteria to be randomized.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
All Participants
All Participants (direct entry and transferred entry) who were enrolled in this study and received intranasal esketamine, matching placebo and oral antidepressant as per the assigned treatment.
Denominators
Units
Counts
Participants
BG000705
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00046.1± 11.1
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000457
Male
BG000248
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG00094
Not Hispanic or Latino
BG000600
Race/Ethnicity, Customized
Count of Participants
Participants
Title
Denominators
Categories
Asian
Title
Measurements
BG0003
Black or African American
Title
Measurements
BG000
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
BELGIUM
Title
Measurements
BG00014
BRAZIL
Title
Measurements
BG000
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
Time to Relapse in Participants With Stable Remission (Maintenance Phase)
Relapse is defined as any of following: Montgomery-asberg depression rating scale (MADRS) total score greater than or equal to (>=) 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable remission: MADRS total score less than or equal to (<=) 12 for at least 3 of last 4 weeks of OP phase, with 1 excursion total score greater than (>) 12 or one missing assessment at OP week 13 or 14.
Full (stable remitters) analysis set included all the randomized participants who were in stable remission at the end of the optimization phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during the maintenance phase.
Posted
Median
95% Confidence Interval
Days
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00090
OG00186
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)Here NA signifies that median and 95%CI was not estimable due to not having sufficient events to meet the threshold for 50% on the Kaplan-Meier curve.
OG001273.0(97.0 to NA)Here NA signifies that upper limit of CI could not be estimated due to insufficient data.
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Weighted Log-rank
= 0.003
Hazard Ratio (HR)
0.49
2-Sided
95
0.29
0.84
Superiority
Secondary
Time to Relapse in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
Relapse is defined as any of following: MADRS total score >= 22 for 2 consecutive assessments separated by 5-15 days and/or hospitalization for worsening depression or any other clinically relevant event to be suggestive of a relapse of depressive illness such as suicide attempt/completed suicide/hospitalization for suicide prevention; If hospitalized, start date of hospitalization will be date of relapse, if not hospitalized date of event will be used. MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal-severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. Stable response is defined as >= 50 percent (%) reduction in MADRS total score from baseline (Day 1 of induction phase, prior to first intranasal dose) in each of the last 2 weeks of the OP phase, but without meeting criteria for stable remission.
Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase.
Posted
Median
95% Confidence Interval
Days
Time from randomization to the first relapse during the maintenance phase (up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (last observation carried forward [LOCF] data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this outcome measure (OM).
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in MADRS Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
MADRS: clinician-rated scale to measure depression severity and to detect changes due to antidepressant treatment. It has 10 items, scored from 0-6 (not present/normal - severe/continuous symptoms), with total score of 60. Higher scores mean more severe condition. The change from baseline in MADRS total score (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable responders) analysis set included all randomized participants who were stable responders (who were not stable remitters) at the end of the optimization phase and who received at least 1 dose of intranasal study drug and 1 dose of oral antidepressant during the maintenance phase.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Patient Health Questionnaire-9 (PHQ-9) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). 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. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in PHQ-9 Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
PHQ-9 is a 9-item, self-report scale assessing depressive symptoms. Each item is rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day). 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. The severity of the PHQ-9 is categorized as follows: None-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19) and severe (20-27). The change from baseline in PHQ-9 total score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Clinical Global Impression-Severity (CGI-S) Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Median
Full Range
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Clinical Global Impression-Severity Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
CGI-S provides an overall clinician-determined summary measure of the severity of the participant's illness that takes into account all available information, including knowledge of the participant's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the participant's ability to function. The CGI-S evaluates the severity of psychopathology on a scale of 0 to 7. Considering total clinical experience, a participant is assessed on severity of mental illness at the time of rating 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 the most extremely ill patients. The change from baseline in CGI-S score, (LOCF data) at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Median
Full Range
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Generalized Anxiety Disorder-7 Items (GAD-7) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Generalized Anxiety Disorder-7 Items Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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). Item responses are summed to yield a total score (range of 0 to 21), with higher scores indicating more anxiety. The change from baseline in GAD-7 total score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) Sum Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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). HSI ranges from 0 (dead) to 1.00 (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.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of optimization phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
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).
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Remission (Maintenance Phase)
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 HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EuroQol-5 Dimension-5 Level Sum Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
EQ-5D-5L 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 HSI. HSI ranges from 0 (dead) to 1.00 (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.
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EQ-5D-5L EQ Visual Analogue Scale Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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).
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in EQ-5D-5L Health Status Index at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
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 HSI. HSI ranges from 0 (dead) to 1.00 (full health).
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Endpoint in Participants With Stable Remission (Maintenance Phase)
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores <= 4 for each item and <= 12 for the total score are considered response. Scores <= 2 for each item and <= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable remitters) analysis set included all randomized participants who were in stable remission at the end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Secondary
Change From Baseline in Sheehan Disability Total Score at Endpoint in Participants With Stable Response (But Not in Stable Remission) (Maintenance Phase)
The SDS is a participant-reported outcome measure and is a 5-item questionnaire used and accepted for assessment of functional impairment and associated disability. The first 3 items assess disruption of 1: work/school 2: social life 3: family life/home responsibilities using a 0-10 rating scale. It also has one item on days lost from school or work and one item on days when underproductive. The score for the first 3 items are summed to create a total score of 0-30 where a higher score indicates greater impairment. The recall period is 7 days. Scores <= 4 for each item and <= 12 for the total score are considered response. Scores <= 2 for each item and <= 6 for the total score are considered remission. The change from baseline in SDS total Score, (LOCF data), at endpoint was reported. The last post baseline observation was carried forward as the endpoint.
Full (stable responders) analysis set: all randomized participants who were stable responders (not stable remitters) at end of OP phase and received at least 1 dose of intranasal study drug and 1 dose of oral AD during MA phase. Here 'N' (overall number of participants analyzed) signifies number of participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline and Endpoint (Up to 92 Weeks)
ID
Title
Description
OG000
Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (DE): received 56 or 84 milligram intranasal esketamine solution twice weekly with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks. OP phase (DE+TE): received intranasal esketamine (same dose) solution once per week for first 4 weeks, then once per week/once every other week based on severity of depressive symptoms, and continued same oral AD from IND phase for 12 weeks. MA phase (DE+TE): Participants were randomized (at end of OP phase) to receive intranasal esketamine (same dose) once weekly/once every other week based on depressive symptoms and continued same oral AD from IND phase. Follow-up (FU) phase: participants received no intranasal esketamine but continued oral AD for 2 weeks unless determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Time Frame
Up to 2 years
Description
Safety analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in respective phase (Induction, Optimization, Maintenance). Follow-up analysis set included all participants who entered the follow-up phase.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
IND: Intranasal Esketamine + Oral AD
Open-label induction (IND) phase (direct-entry participants only): received 56 milligram (mg) or 84 mg intranasal esketamine solution twice weekly with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine extended release [XR]), once daily for 4 weeks.
0
437
13
437
306
437
EG001
OP: Intranasal Esketamine + Oral AD
Optimization (OP) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
0
455
11
455
279
455
EG002
MA: Intranasal Esketamine + Oral AD
Maintenance (MA) phase (both direct-entry and transferred-entry participants): received 56 mg or 84 mg intranasal esketamine solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily until relapse or study termination.
0
152
4
152
114
152
EG003
MA: Oral AD + Intranasal Placebo
Maintenance phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), until relapse or study termination.
0
145
1
145
45
145
EG004
FU: Intranasal Esketamine + Oral AD
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received at least 1 dose of 56 mg or 84 mg intranasal esketamine participated in the follow-up (FU) phase. No intranasal esketamine was administered during FU phase. Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
0
481
3
481
14
481
EG005
FU: Oral AD + Intranasal Placebo
Participants (who were non-responders in IND phase and who were in OP and MA phase at study termination) who received intranasal esketamine matching placebo with oral AD participated in the FU phase. Participants received oral AD for at least the 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate.
0
64
0
64
1
64
EG006
OP_TEP: Oral AD + Intranasal Placebo
OP phase (transferred-entry participants [TEP]): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks.
0
86
0
86
40
86
EG007
MA_TEP: Oral AD + Intranasal Placebo
Maintenance phase (transferred-entry participants): Participants were randomized (at the end of optimization phase) to intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral AD (one of: duloxetine/escitalopram/sertraline/venlafaxine XR).
0
54
1
54
37
54
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Sinus Tachycardia
Cardiac disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG0030 affected145 at risk
EG0040 affected481 at risk
EG0050 affected64 at risk
EG0060 affected86 at risk
EG0070 affected54 at risk
Anal Fissure
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Chest Pain
General disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Hypothermia
General disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Cholecystitis Acute
Hepatobiliary disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Pneumonia
Infections and infestations
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Sepsis
Infections and infestations
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Procedural Pain
Injury, poisoning and procedural complications
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Intervertebral Disc Protrusion
Musculoskeletal and connective tissue disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Pain in Extremity
Musculoskeletal and connective tissue disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Autonomic Nervous System Imbalance
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Lacunar Stroke
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Migraine
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Sedation
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Simple Partial Seizures
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Ectopic Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0021 affected152 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0002 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Depression
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0003 affected437 at risk
EG0011 affected455 at risk
EG0022 affected152 at risk
EG003
Disorientation
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Major Depression
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0021 affected152 at risk
EG003
Mania
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Panic Attack
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Suicidal Ideation
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Hypertensive Crisis
Vascular disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0011 affected455 at risk
EG0020 affected152 at risk
EG003
Orthostatic Hypotension
Vascular disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0001 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Clavicle Fracture
Injury, poisoning and procedural complications
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Vertigo
Ear and labyrinth disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00099 affected437 at risk
EG00191 affected455 at risk
EG00238 affected152 at risk
EG0038 affected145 at risk
EG0042 affected481 at risk
EG0050 affected64 at risk
EG0060 affected86 at risk
EG0070 affected54 at risk
Diplopia
Eye disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00016 affected437 at risk
EG00110 affected455 at risk
EG0029 affected152 at risk
EG003
Vision Blurred
Eye disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00045 affected437 at risk
EG00130 affected455 at risk
EG00224 affected152 at risk
EG003
Hypoaesthesia Oral
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00032 affected437 at risk
EG00134 affected455 at risk
EG00220 affected152 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00094 affected437 at risk
EG00148 affected455 at risk
EG00225 affected152 at risk
EG003
Paraesthesia Oral
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00016 affected437 at risk
EG00113 affected455 at risk
EG0028 affected152 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00029 affected437 at risk
EG00117 affected455 at risk
EG00210 affected152 at risk
EG003
Viral Upper Respiratory Tract Infection
Infections and infestations
MedDRA Version 20.0
Non-systematic Assessment
EG0005 affected437 at risk
EG00122 affected455 at risk
EG00211 affected152 at risk
EG003
Blood Pressure Increased
Investigations
MedDRA Version 20.0
Non-systematic Assessment
EG00034 affected437 at risk
EG00126 affected455 at risk
EG00210 affected152 at risk
EG003
Dizziness
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00097 affected437 at risk
EG00161 affected455 at risk
EG00231 affected152 at risk
EG003
Dizziness Postural
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00033 affected437 at risk
EG00126 affected455 at risk
EG00210 affected152 at risk
EG003
Dysgeusia
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00090 affected437 at risk
EG00179 affected455 at risk
EG00241 affected152 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00060 affected437 at risk
EG00157 affected455 at risk
EG00227 affected152 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00030 affected437 at risk
EG00124 affected455 at risk
EG0029 affected152 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00048 affected437 at risk
EG00123 affected455 at risk
EG00211 affected152 at risk
EG003
Sedation
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00043 affected437 at risk
EG00119 affected455 at risk
EG00210 affected152 at risk
EG003
Somnolence
Nervous system disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00065 affected437 at risk
EG00163 affected455 at risk
EG00232 affected152 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00031 affected437 at risk
EG00111 affected455 at risk
EG00212 affected152 at risk
EG003
Confusional State
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00013 affected437 at risk
EG0019 affected455 at risk
EG0029 affected152 at risk
EG003
Dissociation
Psychiatric disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00082 affected437 at risk
EG00173 affected455 at risk
EG00235 affected152 at risk
EG003
Nasal Discomfort
Respiratory, thoracic and mediastinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00029 affected437 at risk
EG00126 affected455 at risk
EG00211 affected152 at risk
EG003
Throat Irritation
Respiratory, thoracic and mediastinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG00026 affected437 at risk
EG00116 affected455 at risk
EG0028 affected152 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Urinary Tract Infection
Infections and infestations
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Musculoskeletal Pain
Musculoskeletal and connective tissue disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Spinal Pain
Musculoskeletal and connective tissue disorders
MedDRA Version 20.0
Non-systematic Assessment
EG0000 affected437 at risk
EG0010 affected455 at risk
EG0020 affected152 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
If an investigator wishes to publish information from the study, 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 by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00062
OG00159
Title
Denominators
Categories
Title
Measurements
OG000635.0(264.0 to 635.0)
OG00188.0(46.0 to 196.0)
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00089
OG00186
Title
Denominators
Categories
Title
Measurements
OG0007.5± 11.59
OG00112.5± 13.63
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00062
OG00159
Title
Denominators
Categories
Title
Measurements
OG0004.4± 11.38
OG00111.4± 12.00
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00089
OG00186
Title
Denominators
Categories
Title
Measurements
OG0003.3± 5.58
OG0015.9± 7.09
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00061
OG00158
Title
Denominators
Categories
Title
Measurements
OG0001.7± 5.02
OG0014.7± 5.48
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00089
OG00186
Title
Denominators
Categories
Title
Measurements
OG0000.0(-3 to 4)
OG0011.0(-2 to 5)
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00062
OG00158
Title
Denominators
Categories
Title
Measurements
OG0000.0(-2 to 4)
OG0011.0(-3 to 5)
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00089
OG00186
Title
Denominators
Categories
Title
Measurements
OG0002.2± 4.45
OG0014.0± 5.93
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00061
OG00158
Title
Denominators
Categories
Title
Measurements
OG0001.4± 3.76
OG0012.6± 4.26
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00088
OG00186
Title
Denominators
Categories
Title
Measurements
OG0007.5± 11.87
OG00110.9± 14.74
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00088
OG00186
Title
Denominators
Categories
Title
Measurements
OG000-10.4± 20.29
OG001-16.1± 21.80
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00088
OG00186
Title
Denominators
Categories
Title
Measurements
OG000-0.067± 0.1180
OG001-0.096± 0.1484
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00061
OG00158
Title
Denominators
Categories
Title
Measurements
OG0003.0± 8.13
OG0018.4± 13.55
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00061
OG00159
Title
Denominators
Categories
Title
Measurements
OG000-1.3± 15.55
OG001-13.8± 19.81
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00061
OG00158
Title
Denominators
Categories
Title
Measurements
OG000-0.023± 0.0753
OG001-0.073± 0.1383
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.
Units
Counts
Participants
OG00082
OG00177
Title
Denominators
Categories
Title
Measurements
OG0004.7± 7.34
OG0017.2± 10.44
OG001
Oral AD+ Intranasal Placebo
Open-label induction phase: No intervention was administered. Optimization phase (transferred-entry participants): received intranasal esketamine matching placebo solution once per week for the first 4 weeks, then once per week or once every other week depending on severity of depressive symptoms with open-label oral antidepressant (AD) (one of: duloxetine/escitalopram/sertraline/venlafaxine XR), once daily for 12 weeks. Maintenance phase (DE+TE participants): Participants were randomized (at the end of optimization phase) to receive intranasal esketamine placebo with oral AD from optimization phase. Follow-up Phase: Participants received oral AD for 2 weeks of the follow-up phase unless it was determined to not be clinically appropriate. Participants who were non-responders at end of IND phase or who were early terminated at any phase proceeded directly to FU phase.