A Study to Evaluate the Efficacy, Safety and Tolerability... | NCT02918318 | Trialant
NCT02918318
Sponsor
Janssen Pharmaceutical K.K.
Status
Completed
Last Update Posted
Apr 29, 2025Actual
Enrollment
202Actual
Phase
Phase 2
Conditions
Depression
Interventions
Placebo
Intranasal esketamine (28 mg)
Intranasal esketamine (56 mg)
Intranasal esketamine (84 mg)
Countries
Japan
Protocol Section
Identification Module
NCT ID
NCT02918318
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
CR108227
Secondary IDs
ID
Type
Description
Link
54135419TRD2005
Other Identifier
Janssen Pharmaceutical K.K., Japan
Brief Title
A Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Participants With Treatment Resistant Depression
Official Title
A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Subjects With Treatment Resistant Depression
Acronym
Not provided
Organization
Janssen Pharmaceutical K.K.INDUSTRY
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
Dec 12, 2016Actual
Primary Completion Date
Aug 19, 2019Actual
Completion Date
Dec 13, 2019Actual
First Submitted Date
Sep 27, 2016
First Submission Date that Met QC Criteria
Sep 27, 2016
First Posted Date
Sep 28, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 18, 2020
Results First Submitted that Met QC Criteria
Sep 24, 2020
Results First Posted Date
Oct 19, 2020Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
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 Pharmaceutical K.K.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
No
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 evaluate the efficacy of fixed dosed intranasal esketamine compared to intranasal placebo, as an add-on to an oral antidepressant in Japanese participants with treatment-resistant depression (TRD), in improving depressive symptoms.
Detailed Description
Not provided
Conditions Module
Conditions
Depression
Keywords
Not provided
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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
202Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo
Experimental
Participant will receive 1 spray of placebo to each nostril at 0 minute, 5 minutes and 10 minutes.
Drug: Placebo
Esketamine 28 milligram (mg)
Experimental
Participant will receive 1 spray of Esketamine to each nostril at 0 minute and placebo at 5 minutes and 10 minutes.
Drug: Intranasal esketamine (28 mg)
Esketamine 56 mg
Experimental
Participant will receive 1 spray of Esketamine to each nostril at 0 minute, 5 minutes and placebo at 10 minutes.
Drug: Intranasal esketamine (56 mg)
Esketamine 84 mg
Experimental
Participant will receive 1 spray of Esketamine to each nostril at 0 minute, 5 minutes and 10 minutes.
Drug: Intranasal esketamine (84 mg)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Placebo
Drug
Participant will receive 1 spray of placebo to each nostril at 0 minute, 5 minutes and 10 minutes.
Placebo
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Double-Blind (DB) Induction Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.
Baseline (Day 1) up to Day 28 (DB phase) induction
Secondary Outcomes
Measure
Description
Time Frame
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score
A participant is defined as responder (yes=1 and no=0) at a given time point if the percent improvement from baseline in MADRS is greater than or equal to (>=) 50 percent (%). MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
At the start of the screening phase, participant must meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnostic criteria for single-episode major depressive disorder (MDD) or recurrent major depressive disorder (MDD), without psychotic features, based upon clinical assessment and confirmed by the Mini International Neuropsychiatric Interview (MINI). In the case of single-episode MDD, the participant must be diagnosed with persistent depressive disorder, which meets criteria of major depressive episode for a continuous duration of greater than or equal to (>=)2 years, and the same physician from the site must be examining the participant for >=2 years continuously as a primary care physician of the participant
The participant's current major depressive episode, depression symptom severity (MADRS total score greater than or equal to [>=] 28 required), and antidepressant treatment response in the current depressive episode, must be confirmed using the SAFER interview
Participant must be medically stable on the basis of clinical laboratory tests, physical examination, medical history, vital signs (including blood pressure), pulse oximetry, and 12-lead electrocardiogram (ECG) performed in the screening phase
A woman of childbearing potential must have a negative highly sensitive serum Beta (β) human chorionic gonadotropin [β-hCG] test at the start of the screening phase and a negative urine pregnancy test must be obtained before the first dose of study drug on Day 1 of the double-blind induction phase prior to randomization
Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participant participating in clinical studies
Exclusion Criteria:
Participant has received vagal nerve stimulation or has received deep brain stimulation in the current episode of depression
Participant previously received esketamine or ketamine as treatment for their MDD
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 phase
Participant has a history of moderate or severe substance or alcohol use disorder according to DSM-5 criteria, except nicotine or caffeine, within 6 months before the start of the screening phase
Participant has a current or past history of seizure disorder (uncomplicated childhood febrile seizures with no sequelae are not exclusionary)
Ohnishi T, Wakamatsu A, Kobayashi H. Different symptomatic improvement pattern revealed by factor analysis between placebo response and response to Esketamine in treatment resistant depression. Psychiatry Clin Neurosci. 2022 Aug;76(8):377-383. doi: 10.1111/pcn.13379. Epub 2022 Jun 9.
Takahashi N, Yamada A, Shiraishi A, Shimizu H, Goto R, Tominaga Y. Efficacy and safety of fixed doses of intranasal Esketamine as an add-on therapy to Oral antidepressants in Japanese patients with treatment-resistant depression: a phase 2b randomized clinical study. BMC Psychiatry. 2021 Oct 25;21(1):526. doi: 10.1186/s12888-021-03538-y.
See Also Links
Label
URL
A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety and Tolerability of Fixed Doses of Intranasal Esketamine in Japanese Subjects With Treatment Resistant Depression
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Periods
Title
Milestones
Reasons Not Completed
Double-blind Induction Phase: 4 Weeks
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
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
Dec 21, 2018
Aug 18, 2020
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
No data available
No data is available for this block.
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 (28 mg)
Drug
Participant will receive 1 spray of Esketamine to each nostril at 0 minute and placebo at 5 minutes and 10 minutes.
Esketamine 28 milligram (mg)
Intranasal esketamine (56 mg)
Drug
Participant will receive 1 spray of Esketamine to each nostril at 0 minute, 5 minutes and placebo at 10 minutes.
Esketamine 56 mg
Intranasal esketamine (84 mg)
Drug
Participant will receive 1 spray of Esketamine to each nostril at 0 minute, 5 minutes and 10 minutes.
Esketamine 84 mg
Days 2, 8, 15, 22 and 28 (DB induction phase)
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
A participant was considered in remission at a given time point if the MADRS total score <=12. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Days 2, 8, 15, 22 and 28 (DB induction phase)
DB Induction Phase: Percentage of Participants Showing Onset of Clinical Response
A participant was defined as having a clinical response if there was at least 50% improvement from baseline in the MADRS total score with onset by Day 2 that was maintained to Day 28 in DB induction phase. Participants were allowed one excursion (non-response) on Days 8, 15 or 22, provided the score is at least 25% improvement. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Day 2 up to Day 28 (DB induction phase)
DB Induction Phase: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score up to Day 28
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. Values of 0 (not assessed) were excluded from analysis. CGI-S permits global evaluation of participant's condition at given time.
Baseline (Day 1) up to Day 28 (DB induction pahse)
DB Induction Phase: Change From Baseline in Generalized Anxiety Disorder 7-Item Scale (GAD-7) up to Day 28
GAD-7 was 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).
Baseline (Day 1) up to Day 28 (DB induction phase)
DB Induction Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28
SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive.
Baseline (Day 1) to Day 28 (DB induction phase)
Posttreatment Phase: Time to Relapse in Participants With Remission (MADRS Total Score <=12)
Time to relapse in participants with remission at the end of the double-blind phase was defined as the time between induction phase and the first documentation of a relapse event during the posttreatment phase. Relapse was defined as any of the following: 1) MADRS total score >= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse; 2) Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score <=12.
From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
Posttreatment Phase: Time to Relapse in Participants With Response (>=50% Reduction From Baseline in MADRS Total Score) But Who Are Not in Remission
Time to relapse in participants with response (>=50% reduction from baseline in MADRS total score) but who are not in remission was reported. Relapse is defined as any of the following: 1) MADRS total score >= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse. 2)Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score <=12.
From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24
SDS is a participant-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has one item on days lost from school or work and one item on days when under productive. FAS (responders): All randomized participants who received at least 1 dose of intranasal study medication during DB induction phase and who were responders at the end of DB induction phase and entered posttreatment phase
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
A participant was considered in remission at a given time point if the MADRS total score <=12. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Days 8, 15, 22 and 28 (OL induction phase)
OL Induction Phase: Change From Baseline (Prior to the First Dose of OL Induction Phase) in MADRS Total Score up to Endpoint OL Induction Phase (Last Post Baseline Assessment Value During the OL Induction Phase [OL: up to Day 28])
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
Baseline (Prior to first Dose of OL induction phase on Day 1) up to endpoint of OL induction phase (last post baseline assessment value during OL induction phase [OL: up to Day 28])
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. CGI-S permits global evaluation of participant's condition at given time.
Baseline (Prior to first dose of OL induction phase on Day 1), endpoint of OL induction phase (last post baseline assessment value during the OL induction phase [OL: up to Day 28])
Fukui-shi
Japan
Fukuoka
Japan
Gunma
Japan
Hachinohe-shi
Japan
Hachioji-shi
Japan
Hirakata
Japan
Hiratsuka-shi
Japan
Hokkaido
Japan
Ibaraki
Japan
Ichikawa
Japan
Kanzaki-gun
Japan
Karatsu
Japan
Kashihara
Japan
Kawasaki
Japan
Kita-Azumi
Japan
Kita-ku
Japan
Kitakyushu
Japan
Kobe
Japan
Kochi
Japan
Kodaira
Japan
Komoro-shi
Japan
Kumamoto
Japan
Kure
Japan
Kurume-shi
Japan
Kyoto
Japan
Maizuru
Japan
Morioka
Japan
Nagakute
Japan
Nagasaki
Japan
Okayama
Japan
Okinawa
Japan
Osaka
Japan
Sapporo
Japan
Setagaya-ku
Japan
Shibuya-ku
Japan
Shinjuku
Japan
Shinjuku-ku
Japan
Takatsuki-shi
Japan
Toyoake
Japan
Ube
Japan
Yokohama
Japan
Yonago
Japan
FG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
FG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
FG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
FG004
Esketamine: Flexible Dose
OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
FG00041 subjects
FG00140 subjects
FG00241 subjects
FG00380 subjects
FG0040 subjects
Responders
FG00013 subjects
FG00111 subjects
FG00217 subjects
FG00327 subjects
FG0040 subjects
COMPLETED
FG00039 subjects
FG00133 subjects
FG00239 subjects
FG00372 subjects
FG0040 subjects
NOT COMPLETED
FG0002 subjects
FG0017 subjects
FG0022 subjects
FG0038 subjects
FG0040 subjects
Type
Comment
Reasons
Adverse Event
FG0001 subjects
FG0014 subjects
FG0022 subjects
FG0033 subjects
FG0040 subjects
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Withdrawal by Subject
FG0001 subjects
FG0011 subjects
FG0020 subjects
FG0030 subjects
FG004
Non-compliance
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG004
Other
FG0000 subjects
FG0012 subjects
FG0020 subjects
FG0031 subjects
FG004
Double-blind Follow-up Phase: 4 Weeks
Type
Comment
Milestone Data
STARTED
FG00027 subjects
FG00128 subjects
FG00224 subjects
FG00353 subjects
FG0040 subjects
COMPLETED
FG00026 subjects
FG00128 subjects
FG00223 subjects
FG00350 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0010 subjects
FG0021 subjects
FG0033 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Posttreatment Phase: Up to 24 Weeks
Type
Comment
Milestone Data
STARTED
FG00013 subjects
FG00111 subjects
FG00217 subjects
FG00327 subjects
FG0040 subjects
COMPLETED
FG00012 subjects
FG0018 subjects
FG00216 subjects
FG00325 subjects
FG004
NOT COMPLETED
FG0001 subjects
FG0013 subjects
FG0021 subjects
FG0032 subjects
FG004
Type
Comment
Reasons
Withdrawal by Subject
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG003
Open Label Treatment Phase: 4 Weeks
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00448 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Open Label Follow-up Phase: 4 Weeks
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG00448 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Full analysis set (FAS) included all randomized participants who received at least 1 dose of intranasal study agent.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
BG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
BG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
BG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
BG004
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00041
BG00140
BG00241
BG00380
BG004202
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
BG00045.9± 9.97
BG00142.5± 8.36
BG00241.9± 10.26
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00023
BG00116
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Region of Enrollment
Count of Participants
Participants
Title
Denominators
Categories
JAPAN
Title
Measurements
BG00041
BG00140
BG002
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
Double-Blind (DB) Induction Phase: Change From Baseline in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score up to Day 28
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.
Full analysis set (FAS [DB]) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, N (Number of participants analyzed) signifies those participants who were evaluable for this outcome measure (OM).
Posted
Mean
Standard Deviation
Units on a scale
Baseline (Day 1) up to Day 28 (DB phase) induction
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00039
OG00134
OG00239
OG003
Title
Denominators
Categories
Title
Measurements
OG000-15.2± 13.07
OG001-14.5± 10.53
OG002-15.1± 12.21
OG003
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
OG003
Dunnett adjustment
0.475
1-sided
Difference of Least Squares means
-1.0
Standard Error of the Mean
2.25
2-Sided
90
-5.77
3.70
Superiority
OG001
OG003
Dunnett adjustment
Secondary
DB Induction Phase: Percentage of Participants With Response Based on MADRS Total Score
A participant is defined as responder (yes=1 and no=0) at a given time point if the percent improvement from baseline in MADRS is greater than or equal to (>=) 50 percent (%). MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.
Posted
Number
Percentage of participants
Days 2, 8, 15, 22 and 28 (DB induction phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
DB Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
A participant was considered in remission at a given time point if the MADRS total score <=12. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
FAS (DB) included all randomized defined as all participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.
Posted
Number
Percentage of participants
Days 2, 8, 15, 22 and 28 (DB induction phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
DB Induction Phase: Percentage of Participants Showing Onset of Clinical Response
A participant was defined as having a clinical response if there was at least 50% improvement from baseline in the MADRS total score with onset by Day 2 that was maintained to Day 28 in DB induction phase. Participants were allowed one excursion (non-response) on Days 8, 15 or 22, provided the score is at least 25% improvement. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during DB induction phase. Participants with missed assessments or discontinued early were not considered to have onset of clinical response. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.
Posted
Number
Percentage of participants
Day 2 up to Day 28 (DB induction phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
DB Induction Phase: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Total Score up to Day 28
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. Values of 0 (not assessed) were excluded from analysis. CGI-S permits global evaluation of participant's condition at given time.
FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.
Posted
Median
Full Range
Units on a scale
Baseline (Day 1) up to Day 28 (DB induction pahse)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
DB Induction Phase: Change From Baseline in Generalized Anxiety Disorder 7-Item Scale (GAD-7) up to Day 28
GAD-7 was 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).
FAS included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline (Day 1) up to Day 28 (DB induction phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
DB Induction Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score up to Day 28
SDS is a participant-reported outcome measure and 5 item questionnaire used for assessment of functional impairment and associated disability. First three items assess disruption of 1 work/school, 2 social life, 3 family life/home responsibilities using a 0(no impairment)-10 (most severe impairment). Score for first 3 items are summed to create total score of 0-30 where higher score indicates greater impairment and a negative change in score indicates improvement. It also has one item on days lost from school or work and one item on days when under productive.
FAS (DB) included all randomized participants who received at least 1 dose of intranasal study agent during the DB induction phase. Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM.
Posted
Mean
Standard Deviation
Units on a scale
Baseline (Day 1) to Day 28 (DB induction phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
Posttreatment Phase: Time to Relapse in Participants With Remission (MADRS Total Score <=12)
Time to relapse in participants with remission at the end of the double-blind phase was defined as the time between induction phase and the first documentation of a relapse event during the posttreatment phase. Relapse was defined as any of the following: 1) MADRS total score >= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse; 2) Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score <=12.
Population included participants with remit at the end of DB.
Posted
Median
90% Confidence Interval
Days
From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
Posttreatment Phase: Time to Relapse in Participants With Response (>=50% Reduction From Baseline in MADRS Total Score) But Who Are Not in Remission
Time to relapse in participants with response (>=50% reduction from baseline in MADRS total score) but who are not in remission was reported. Relapse is defined as any of the following: 1) MADRS total score >= 22 for 2 consecutive assessments. The date of the second MADRS assessment was used for the date of relapse. 2)Hospitalization for worsening depression or any other clinically relevant event determined per clinical judgment to be suggestive of relapse of depressive illness like suicide attempt, completed suicide, or hospitalization for suicide prevention. If hospitalized for any of these events, start date of hospitalization was used as relapse date. If participant was not hospitalized, event date was used. 3) If both relapse criteria were met, earlier date was defined as date of relapse. Remission was defined as MADRS total score <=12.
Population included participants with response (not remit) at the end of DB.
Posted
Median
90% Confidence Interval
Days
From EndPoint (last post baseline assessment value during the DB induction phase [up to Day 28]) up to 24 weeks (posttreatment phase)
ID
Title
Description
OG000
Esketamine 28 Milligrams (mg)
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
Posttreatment Phase: Change From Baseline in Sheehan Disability Scale (SDS) Total Score at Weeks 2, 4, 6, 8, 12, 16, 20 and 24
SDS is a participant-reported outcome measure and is a 5-item questionnaire which has been widely used and accepted for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, and (3) family life/home responsibilities using a 0-10 rating scale. The score for the first three items are summed to create a total score of 0-30, where a higher score indicates greater impairment. It also has one item on days lost from school or work and one item on days when under productive. FAS (responders): All randomized participants who received at least 1 dose of intranasal study medication during DB induction phase and who were responders at the end of DB induction phase and entered posttreatment phase
Here, 'N' (number of participants analyzed) signifies participants who were evaluable for this OM. Here, 'n' (number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.
Double-blind (DB) induction phase: Participants received intranasal esketamine (Esk) 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
Secondary
OL Induction Phase: Percentage of Participants With Remission Based on MADRS Total Score
A participant was considered in remission at a given time point if the MADRS total score <=12. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
FAS (OL) included all randomized participants who received at least 1 dose of intranasal study agent during the OL induction phase. Here 'n' (Number analyzed) signifies number of participants who were evaluable for this OM at specified timepoints.
Posted
Number
Percentage of participants
Days 8, 15, 22 and 28 (OL induction phase)
ID
Title
Description
OG000
Esketamine: Flexible Dose
OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
Secondary
OL Induction Phase: Change From Baseline (Prior to the First Dose of OL Induction Phase) in MADRS Total Score up to Endpoint OL Induction Phase (Last Post Baseline Assessment Value During the OL Induction Phase [OL: up to Day 28])
MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition.
FAS (OL) included all participants who received at least 1 dose of intranasal study agent during the OL induction phase.
Posted
Mean
Standard Deviation
Units on a scale
Baseline (Prior to first Dose of OL induction phase on Day 1) up to endpoint of OL induction phase (last post baseline assessment value during OL induction phase [OL: up to Day 28])
ID
Title
Description
OG000
Esketamine: Flexible Dose
OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
Secondary
OL Induction Phase: Percentage of Participants With Severity of Psychopathology on the CGI-S Scale
CGI-S provides measure of severity of participant's illness including participant's history, psychosocial circumstances, symptoms, behavior and impact of symptoms on ability to function. CGI-S evaluates severity of psychopathology on scale of 0 to 7. Considering total clinical experience, participant is assessed on severity of mental illness according to: 0=not assessed; 1=normal (not at all ill); 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among most extremely ill patients. CGI-S permits global evaluation of participant's condition at given time.
FAS (OL) included all participants who received at least 1 dose of intranasal study agent during the OL induction phase.
Posted
Number
Percentage of participants
Baseline (Prior to first dose of OL induction phase on Day 1), endpoint of OL induction phase (last post baseline assessment value during the OL induction phase [OL: up to Day 28])
ID
Title
Description
OG000
Esketamine: Flexible Dose
OL induction phase: Responders from the DB induction phase who relapsed in the postreatment phase entered in an open label extension phase and received induction with flexible intransal Esketamine (either 28 mg, 56 mg, or 84 mg) along with oral AD for 4 weeks. OL Follow-up phase: All participants who entered the OL induction phase are followed up in OL follow-up phase for 4 weeks.
Time Frame
Up to 42 weeks
Description
There was 1 participant who was randomized to the Esk 84 mg group but was dosed Esk 56 mg on Days 1 and 4, and Esk 28 mg on Day 8, then withdrew due to an adverse event on Day 11. This participant was summarized under the Esk 56 mg group for safety analyses.
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
Double Blind (DB): Esketamine 28 mg
Participants received intranasal esketamine 28 mg twice a week add-on to an oral antidepressant (AD) for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.
0
41
1
41
33
41
EG001
DB: Esketamine 56 mg
Participants received intranasal esketamine 56 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk DB induction phase.
0
41
0
41
39
41
EG002
DB: Esketamine 84 mg
Participants received intranasal esketamine 84 mg twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received at least 1 dose of Esk during DB induction phase.
0
40
1
40
39
40
EG003
DB: Placebo
Participants received intranasal placebo twice a week add-on to an oral AD for 4 weeks. Analysis was performed on safety analysis set- all randomized participants who received dose of internasal placebo during DB induction phase.
0
80
1
80
34
80
EG004
DB Follow Up (FU): Esketamine 28 mg
Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD for 4 weeks. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.
0
27
0
27
3
27
EG005
DB FU: Esketamine 56 mg
Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.
0
29
0
29
3
29
EG006
DB FU: Esketamine 84 mg
Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.
0
23
1
23
3
23
EG007
DB FU: Placebo
Participants who were non responders at the end of DB induction phase and entered the DB follow-up phase received only oral AD in the DB FU phase. Analysis was performed on follow-up analysis set- all participants who entered the follow-up phase and were evaluated for the safety.
0
53
2
53
7
53
EG008
Post-Treatment (PT) Phase: Esketamine 28 mg
Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.
0
13
0
13
6
13
EG009
PT Phase: Esketamine 56 mg
Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.
0
11
0
11
4
11
EG010
PT Phase: Esketamine 84 mg
Participants who were responders at the end of DB induction phase and entered in the PT phase received only an oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.
0
17
0
17
6
17
EG011
PT Phase: Placebo
Participants who were responders at the end of DB induction phase and entered in the PT phase received only oral AD in the PT phase. Analysis was performed on safety analysis set- All participants who received at least 1 dose of oral AD during PT phase.
0
27
0
27
7
27
EG012
Open-Label (OL): Flexible Esketamine
Participants received flexible esketamine add-on to an oral AD during OL induction phase for 4 weeks. Analysis was performed on safety analysis set- All participants who received at least 1 dose of flexible Esk during OL induction phase.
0
48
1
48
47
48
EG013
OL FU: Flexible Esketamine
Participants who received flexible esketamine add-on to an oral AD during OL induction phase were followed for 4 weeks in OL FU phase. Analysis was performed on follow-up analysis set- all participants who entered the OL follow-up phase and were evaluated for the safety.
0
48
2
48
3
48
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Atrioventricular Block Second Degree
Cardiac disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG0030 affected80 at risk
EG004
Ankle Fracture
Injury, poisoning and procedural complications
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Fracture
Injury, poisoning and procedural complications
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Muscular Weakness
Musculoskeletal and connective tissue disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Uterine Leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Cerebral Disorder
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Suicidal Ideation
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0021 affected40 at risk
EG003
Suicide Attempt
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Palpitations
Cardiac disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0012 affected41 at risk
EG0022 affected40 at risk
EG0031 affected80 at risk
EG0040 affected27 at risk
EG0050 affected29 at risk
EG0060 affected23 at risk
EG0071 affected53 at risk
EG0081 affected13 at risk
EG0090 affected11 at risk
EG0100 affected17 at risk
EG0110 affected27 at risk
EG0120 affected48 at risk
EG0130 affected48 at risk
Hyperacusis
Ear and labyrinth disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0011 affected41 at risk
EG0022 affected40 at risk
EG003
Tinnitus
Ear and labyrinth disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0004 affected41 at risk
EG0017 affected41 at risk
EG0028 affected40 at risk
EG003
Conjunctivitis Allergic
Eye disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Diplopia
Eye disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0013 affected41 at risk
EG0020 affected40 at risk
EG003
Dry Eye
Eye disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0011 affected41 at risk
EG0020 affected40 at risk
EG003
Visual Impairment
Eye disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0012 affected41 at risk
EG0020 affected40 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0014 affected41 at risk
EG0022 affected40 at risk
EG003
Hypoaesthesia Oral
Gastrointestinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0003 affected41 at risk
EG0012 affected41 at risk
EG0022 affected40 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0007 affected41 at risk
EG0017 affected41 at risk
EG0028 affected40 at risk
EG003
Stomatitis
Gastrointestinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0002 affected41 at risk
EG0011 affected41 at risk
EG0020 affected40 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0013 affected41 at risk
EG0024 affected40 at risk
EG003
Asthenia
General disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0002 affected41 at risk
EG0017 affected41 at risk
EG0023 affected40 at risk
EG003
Feeling Drunk
General disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0015 affected41 at risk
EG0022 affected40 at risk
EG003
Malaise
General disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0013 affected41 at risk
EG0023 affected40 at risk
EG003
Thirst
General disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0010 affected41 at risk
EG0021 affected40 at risk
EG003
Muscle Strain
Injury, poisoning and procedural complications
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Blood Pressure Diastolic Increased
Investigations
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Blood Pressure Increased
Investigations
MedDRA Version 22.0
Non-systematic Assessment
EG00012 affected41 at risk
EG00119 affected41 at risk
EG00219 affected40 at risk
EG003
Respiratory Rate Decreased
Investigations
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Weight Increased
Investigations
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Muscular Weakness
Musculoskeletal and connective tissue disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0012 affected41 at risk
EG0022 affected40 at risk
EG003
Dizziness
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG00011 affected41 at risk
EG00118 affected41 at risk
EG00215 affected40 at risk
EG003
Dizziness Postural
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0013 affected41 at risk
EG0022 affected40 at risk
EG003
Dysarthria
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Dyslalia
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0022 affected40 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0006 affected41 at risk
EG0015 affected41 at risk
EG0024 affected40 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0007 affected41 at risk
EG0018 affected41 at risk
EG0025 affected40 at risk
EG003
Hypotonia
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0023 affected40 at risk
EG003
Mental Impairment
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0003 affected41 at risk
EG0012 affected41 at risk
EG0020 affected40 at risk
EG003
Sedation
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0001 affected41 at risk
EG0014 affected41 at risk
EG0025 affected40 at risk
EG003
Somnolence
Nervous system disorders
MedDRA Version 22.0
Non-systematic Assessment
EG00010 affected41 at risk
EG00113 affected41 at risk
EG00211 affected40 at risk
EG003
Agitation
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0012 affected41 at risk
EG0021 affected40 at risk
EG003
Depersonalisation/Derealisation Disorder
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0012 affected41 at risk
EG0020 affected40 at risk
EG003
Dissociation
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG00014 affected41 at risk
EG00110 affected41 at risk
EG00222 affected40 at risk
EG003
Euphoric Mood
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0014 affected41 at risk
EG0023 affected40 at risk
EG003
Hallucination
Psychiatric disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0011 affected41 at risk
EG0022 affected40 at risk
EG003
Albuminuria
Renal and urinary disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Dyspnoea
Respiratory, thoracic and mediastinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Oropharyngeal Pain
Respiratory, thoracic and mediastinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0011 affected41 at risk
EG0022 affected40 at risk
EG003
Rhinitis Allergic
Respiratory, thoracic and mediastinal disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Night Sweats
Skin and subcutaneous tissue disorders
MedDRA Version 22.0
Non-systematic Assessment
EG0000 affected41 at risk
EG0010 affected41 at risk
EG0020 affected40 at risk
EG003
Esk has transient dissociative effects that are difficult to blind, these specific events could have biased clinical staff who observed treatment sessions. To ensure an unbiased efficacy evaluation, remote, blinded MADRS raters were used.
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.
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00041
OG00140
OG00241
OG00380
Title
Denominators
Categories
Day 2
ParticipantsOG00041
ParticipantsOG00138
ParticipantsOG00240
ParticipantsOG00379
Title
Measurements
OG00022.0
OG00113.2
OG00210.0
OG003
Day 8
ParticipantsOG00041
ParticipantsOG00139
ParticipantsOG00241
ParticipantsOG00379
Day 15
ParticipantsOG00040
ParticipantsOG00136
ParticipantsOG00240
ParticipantsOG00377
Day 22
ParticipantsOG00039
ParticipantsOG00136
ParticipantsOG00239
ParticipantsOG00374
Day 28
ParticipantsOG00039
ParticipantsOG00134
ParticipantsOG00239
ParticipantsOG00372
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00041
OG00140
OG00241
OG00380
Title
Denominators
Categories
Day 2
ParticipantsOG00041
ParticipantsOG00138
ParticipantsOG00240
ParticipantsOG00378
Title
Measurements
OG0009.8
OG0010
OG0027.5
OG003
Day 8
ParticipantsOG00041
ParticipantsOG00139
ParticipantsOG00241
ParticipantsOG00379
Day 15
ParticipantsOG00040
ParticipantsOG00136
ParticipantsOG00240
ParticipantsOG00377
Day 22
ParticipantsOG00039
ParticipantsOG00136
ParticipantsOG00239
ParticipantsOG00374
Day 28
ParticipantsOG00039
ParticipantsOG00134
ParticipantsOG00239
ParticipantsOG00372
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00041
OG00139
OG00241
OG00379
Title
Denominators
Categories
Onset of clinical response: Yes
Title
Measurements
OG0002.4
OG0012.6
OG0027.3
OG0036.3
Onset of clinical response: No
Title
Measurements
OG00097.6
OG00197.4
OG00292.7
OG003
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00039
OG00133
OG00239
OG00372
Title
Denominators
Categories
Title
Measurements
OG000-1.0(-5 to 1)
OG001-1.0(-3 to 0)
OG002-1.0(-5 to 0)
OG003-1.0(-4 to 1)
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00039
OG00135
OG00239
OG00373
Title
Denominators
Categories
Title
Measurements
OG000-8.2± 4.94
OG001-7.8± 5.05
OG002-8.1± 5.67
OG003-7.7± 5.05
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00030
OG00129
OG00231
OG00353
Title
Denominators
Categories
Title
Measurements
OG000-8.6± 8.68
OG001-7.9± 7.94
OG002-9.5± 8.93
OG003-7.0± 7.39
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG0009
OG0014
OG0029
OG00315
Title
Denominators
Categories
Title
Measurements
OG00034.0(26.0 to NA)Upper limit of 90 % confidence internal was not estimable due to insufficient number of participants with events.
OG00152.0(20.0 to 80.0)
OG00237.0(19.0 to 71.0)
OG00330.0(22.0 to 50.0)
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.
Units
Counts
Participants
OG00013
OG00111
OG00217
OG00327
Title
Denominators
Categories
Title
Measurements
OG00032.0(13.0 to 44.0)
OG00126.0(9.0 to 121.0)
OG00279.5(16.0 to 108.0)
OG00391.0(22.0 to NA)Upper limit of 90 % confidence internal was not estimable due to insufficient number of participants with events.
OG001
Esketamine 56 mg
DB induction phase: Participants received intranasal Esk 56 mg twice a week add-on to a AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG002
Esketamine 84 mg
DB induction phase: Participants received intranasal Esk 84 mg twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for up to 24 weeks.
OG003
Placebo
DB induction phase: Participants received intranasal Esk placebo twice a week add-on to AD for 4 weeks. Responders (participants who had >=50% reduction from baseline in MADRS total score) at the end of the DB induction phase were eligible to proceed to the posttreatment. DB Follow-up Phase: Participants who did not respond (non-responders) in DB induction phase proceeded to the 4-week DB follow-up and received only oral AD. Posttreatment phase: Participants who were responders at the end of DB induction phase entered in posttreatment phase and received oral AD once daily for 24 weeks.