Trial Outcomes & Findings for A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression (NCT NCT02497287)

Last Updated: 2025-04-29

Results Overview

The ONB is a measure of working memory and scored for speed of correct response (mean of the log10-transformed reaction times for correct responses). Total score ranges from 2 to 3.54 log10 msec. Lower score indicates better performance. Higher change from baseline indicates better performance.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

802 participants

Primary outcome timeframe

Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

Results posted on

2025-04-29

Participant Flow

In this study participants from study ESKETINTRD3005 (NCT02422186) were enrolled (transferred entry \[TE\]). ESKETINTRD3005 is referred as TRD3005 in the draft.

Total 802 participants were enrolled (direct-entry \[DE\]=691 + TE from study ESKETINTRD3005 =111). Among 111 TE participants, 88 participants (non-responders from ESKETINTRD3005) joined induction (IND) phase and 23 participants (responders from ESKETINTRD3005) did not join IND phase and directly entered in optimization/maintenance (OP/MA) phase.

Participant milestones

Participant milestones
Measure	Intranasal Esketamine + Oral Antidepressant Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Induction Phase (4 Weeks) STARTED	779
Induction Phase (4 Weeks) COMPLETED	580
Induction Phase (4 Weeks) NOT COMPLETED	199
Optimization/Maintenance (48 Weeks) STARTED	603
Optimization/Maintenance (48 Weeks) COMPLETED	150
Optimization/Maintenance (48 Weeks) NOT COMPLETED	453
Follow-up Phase (4 Week) STARTED	357
Follow-up Phase (4 Week) COMPLETED	326
Follow-up Phase (4 Week) NOT COMPLETED	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Intranasal Esketamine + Oral Antidepressant Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Induction Phase (4 Weeks) Did Not Met Criteria for OP/MA Phase	84
Induction Phase (4 Weeks) Adverse Event	52
Induction Phase (4 Weeks) Withdrawal by Subject	22
Induction Phase (4 Weeks) Lack of Efficacy	21
Induction Phase (4 Weeks) Other	13
Induction Phase (4 Weeks) Lost to Follow-up	5
Induction Phase (4 Weeks) Protocol Violation	1
Induction Phase (4 Weeks) Non-Compliance with Study Drug	1
Optimization/Maintenance (48 Weeks) Study Terminated by Sponsor	331
Optimization/Maintenance (48 Weeks) Withdrawal by Subject	30
Optimization/Maintenance (48 Weeks) Adverse Event	25
Optimization/Maintenance (48 Weeks) Lack of Efficacy	25
Optimization/Maintenance (48 Weeks) Other	21
Optimization/Maintenance (48 Weeks) Lost to Follow-up	10
Optimization/Maintenance (48 Weeks) Protocol Violation	3
Optimization/Maintenance (48 Weeks) Missed Assessment or Treatment Sessions	3
Optimization/Maintenance (48 Weeks) Pregnancy	2
Optimization/Maintenance (48 Weeks) Death	2
Optimization/Maintenance (48 Weeks) Non-Compliance with Study Drug	1
Follow-up Phase (4 Week) PI Decision	12
Follow-up Phase (4 Week) Withdrawal by Subject	10
Follow-up Phase (4 Week) Lost to Follow-up	5
Follow-up Phase (4 Week) Adverse Event	3
Follow-up Phase (4 Week) Other	1

Baseline Characteristics

A Long-term, Safety and Efficacy Study of Intranasal Esketamine in Treatment-resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Intranasal Esketamine + Oral Antidepressant n=802 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Age, Continuous	52.2 years STANDARD_DEVIATION 13.69 • n=5 Participants
Sex: Female, Male Female	502 Participants n=5 Participants
Sex: Female, Male Male	300 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	149 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	640 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	13 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	81 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	15 Participants n=5 Participants
Race (NIH/OMB) White	686 Participants n=5 Participants
Race (NIH/OMB) More than one race	8 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	12 Participants n=5 Participants
Region of Enrollment ARGENTINA	106 Participants n=5 Participants
Region of Enrollment AUSTRALIA	23 Participants n=5 Participants
Region of Enrollment AUSTRIA	16 Participants n=5 Participants
Region of Enrollment BELGIUM	5 Participants n=5 Participants
Region of Enrollment BRAZIL	52 Participants n=5 Participants
Region of Enrollment BULGARIA	94 Participants n=5 Participants
Region of Enrollment FINLAND	2 Participants n=5 Participants
Region of Enrollment FRANCE	4 Participants n=5 Participants
Region of Enrollment GERMANY	13 Participants n=5 Participants
Region of Enrollment ITALY	7 Participants n=5 Participants
Region of Enrollment MALAYSIA	19 Participants n=5 Participants
Region of Enrollment MEXICO	10 Participants n=5 Participants
Region of Enrollment POLAND	6 Participants n=5 Participants
Region of Enrollment SOUTH AFRICA	64 Participants n=5 Participants
Region of Enrollment SOUTH KOREA	26 Participants n=5 Participants
Region of Enrollment SPAIN	42 Participants n=5 Participants
Region of Enrollment SWEDEN	90 Participants n=5 Participants
Region of Enrollment TAIWAN	33 Participants n=5 Participants
Region of Enrollment TURKEY	31 Participants n=5 Participants
Region of Enrollment UNITED KINGDOM	12 Participants n=5 Participants
Region of Enrollment UNITED STATES	147 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to End of Follow up Phase (Week 56)

An adverse event is any untoward medical occurrence in a clinical study participants who administered a medicinal (investigational or non-investigational) product and does not necessarily have a causal relationship with the treatment. A TEAE defined as an event that was new in onset or increased in severity following treatment initiation.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=802 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)	90.1 Percentage of participants

PRIMARY outcome

Timeframe: Up to End of Follow up Phase (Week 56)

Percentage of participants with cystitis, urinary tract infections, renal and urinary tract symptoms, renal and urinary disorders were evaluated. Cystitis and urinary tract infections are selected MedDRA preferred terms, "renal and urinary tract symptoms" refers to any preferred term (PT) in the group of selected PTs; and "renal and urinary disorders" refers to a MedDRA System Organ Class (SOC).

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=802 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders Cystitis	0.6 Percentage of participants
Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders Urinary tract infections	8.1 Percentage of participants
Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders Renal and urinary disorders	10.5 Percentage of participants
Percentage of Participants With Cystitis, Urinary Tract Infections, Renal and Urinary Tract Symptoms, Renal and Urinary Disorders Renal and urinary tract symptoms	17.0 Percentage of participants

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of Optimization/Maintenance [OP/MA] Phase)

Population: All enrolled analysis set included all transferred-entry and direct-entry participants who were not screen failures and received at least one dose of intranasal study medication or 1 dose of oral antidepressant. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. The DET is a measure of psychomotor function and uses a well-validated simple reaction time. In this outcome measure, speed of performance of participants (calculated as mean of the logarithmic base 10 transformed reaction times) for correct responses was reported. Total score ranges from 2 to 3.3 log 10 milliseconds (msec). Lower score indicates better performance. Higher change from baseline indicates better performance.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=561 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Cognitive Test Battery: Detection Test (DET) Score	-0.0028 log10 msec Standard Deviation 0.12744

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. IDN test is a measure of visual attention (choice reaction time) and scored for speed of response (mean of the log10 transformed reaction times for correct responses). Total score ranges from 2 to 3.3 log 10 msec. Lower score indicates better performance. Higher change from baseline indicates better performance.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=561 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Cognitive Test Battery: Identification Test (IDN) Score	-0.0083 log10 msec Standard Deviation 0.09656

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. OCL test is a measure of visual episodic memory and visual recall test scored using arcsine transformation of the percentage of correct responses (CR). The range for OCL is 0 to 100 percent (%) accuracy; presented as an arcsin transformation, the range is 0 to 1.57. Higher score indicates better performance. Higher change from baseline indicates better performance.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=561 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Cognitive Test Battery: One Card Learning Test (OCL) Score	0.0502 Arcsine ([sqrt] of proportion of [CR]) Standard Deviation 0.13149

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=563 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Cognitive Test Battery: One Back Test (ONB) Score	0.0177 log10 msec Standard Deviation 0.10026

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

This battery is a series of computerized cognition tests (detection, identification, one card learning, one back and groton maze learning) designed to measure reaction time, visual learning and memory, and executive function/sequencing. GMLT measures executive function; maze/sequencing test, scored for total number of errors. Total score ranges from 0 to 999 number of errors. Lower score indicates better performance. Higher change from baseline indicates better performance.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=506 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Cognitive Test Battery: Groton Maze Learning Test (GMLT) Score	6.9 Number of Errors Standard Deviation 25.36

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

Hopkins Verbal Learning Test (HVLT) measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=569 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Total Recall	2.8 Number correct Standard Deviation 4.74

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

HVLT measures performance in verbal memory, learning, and long-term recall in which a list of words is read up to three times. Approximately 20-25 minutes later, a delayed recall trial and a recognition trial are completed. The delayed recall requires free recall of any words remembered. The recognition trial is composed of 24 words, including the 12 target words and 12 false-positives. When scoring the HVLT, the three learning trials are combined to calculate a total recall score (0-36); the delayed recall trial creates the delayed recall score (0 -12); the retention (%) score (0-100%) is calculated by dividing the delayed recall trial by the higher of learning trial 2 or 3; and the recognition discrimination index is comprised by subtracting the total number of false positives from the total number of true positives. A higher score = higher cognition.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=569 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Delayed Recall	0.8 Number correct Standard Deviation 2.31

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=568 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Number of Words Recalled	0.3 Number of words recalled Standard Deviation 2.83

PRIMARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=568 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Hopkins Verbal Learning Test-Revised (HVLT-R) Score: Recognition Discrimination Index	0.5 Number of words Standard Deviation 3.16

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Population: The full (IND) analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral AD in open-label IND phase (for direct-entry and transferred-entry non-responder participants). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using last observation carried forward (LOCF) method, last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=756 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in Montgomery Asberg Depression Rating Scale (MADRS) Total Score During Induction (IND) Phase	-16.4 Units on a Scale Standard Deviation 8.76

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA Phase)

Population: Full (OP/MA) analysis set: All participants who received at least 1 dose of intranasal study medication or 1 dose of oral AD in the OP/MA phase.

MADRS measure depression severity, detects changes due to AD treatment. It evaluates 10 items: apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts, each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores represent a more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in MADRS Total Score During Optimization/Maintenance (OP/MA) Phase	0.3 Units on a Scale Standard Deviation 8.12

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Population: Full (IND) analysis set: All participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the open-label IND phase (for direct-entry and transferred-entry non-responder participants). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. A higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=746 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in Patient Health Questionnaire - 9 (PHQ-9) Total Score During IND Phase	-8.9 Unit on a Scale Standard Deviation 6.67

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: Full (OP/MA) analysis set: All participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the OP/MA phase.

PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. A higher score indicates greater severity of depression. severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in PHQ-9 Total Score During OP/MA Phase	-0.2 Units on a Scale Standard Deviation 5.65

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Population: Full (IND) analysis set: All participants who received at least 1 dose of intranasal study medication or 1 dose of oral AD in the open-label IND phase (for direct-entry and transferred-entry non-responder participants). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

CGI-S measures severity of participant's illness that include knowledge of participant's history, psychosocial circumstances, symptoms, behavior, impact of symptoms on participant's ability to function. CGI-S evaluates severity of psychopathology on a scale range from 0 - 7, where 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. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=763 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in Clinical Global Impression of Severity (CGI-S) Scale Score During IND Phase	-2.0 Units on a Scale Interval -6.0 to 2.0

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the OP/MA phase.

The CGI-S measures the severity of the participant's illness that include 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, where 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. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in CGI-S Scale Score During OP/MA Phase	0.0 Units on a Scale Interval -3.0 to 4.0

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Population: The full (IND) analysis set included all participants who received at least 1 dose of intranasal study drug or 1 dose of oral AD in the open-label IND phase (for direct-entry and transferred-entry non-responder participants). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

GAD-7 is brief, validated 7-item self-reported assessment of overall anxiety. Participant's responded to each item using a 4 point scale with response categories: 0=not at all, 1=several days, 2=more than half the days, and 3=nearly every day. Item responses are summed to yield total score ranges from 0 to 21, higher scores indicate more anxiety. Negative change in score indicates improvement. Severity of GAD-7 is categorized as: None (0-4), Mild (5-9), Moderate (10-14), Severe (15 -21). Missing data was imputed using LOCF method, last post baseline observation during the phase was carried forward as "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=724 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in Generalized Anxiety Disorder (GAD-7) Total Score During IND Phase	-5.9 Units on a Scale Standard Deviation 5.85

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: Full (OP/MA) analysis set: All participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the OP/MA phase. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

GAD-7 is brief and validated 7-item self-reported assessment of overall anxiety. Participants respond to each item using a 4 point scale with response categories: 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 ranges from 0 to 21, higher scores indicate more anxiety. Negative change in score indicates improvement. Severity of the GAD-7 is categorized as follows: None (0-4), Mild (5-9), Moderate (10-14), Severe (15 -21). Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=574 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in GAD-7 Total Score During OP/MA Phase	0.2 Units on a Scale Standard Deviation 4.23

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Population: The full (IND) analysis set included all participants who received at least 1 dose of intranasal study drug or 1 dose of oral AD in the open-label IND phase (direct-entry, transferred-entry non-responder participants). Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

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 -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=745 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During IND Phase: Sum Score	-15.3 Units on a Scale Standard Deviation 16.26

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

EQ-5D-5L consists of EQ-5D-5L descriptive system and EQ VAS. 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).

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=746 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in EQ-5D-5L Score During IND Phase: EQ-VAS	17.0 Units on a Scale Standard Deviation 21.69

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=745 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in EQ-5D-5L Scale Score During IND Phase: Health Status Index	0.190 Units on a Scale Standard Deviation 0.2138

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study drug or 1 dose of oral AD in OP/MA 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 Health Status Index (HSI). HSI ranges from -0.148 to 0.949 and is anchored at 0 (health state value equal to dead) and 1 (full health). EQ VAS self-rating records the respondent's own assessment of his/her overall health status at time of completion, on a scale of 0 (worst health you can imagine) to 100 (best health you can imagine). Sum score ranges from 0 to 100 where, sum score = (sum of the scores from the 5 dimensions minus 5) \*5. Higher score indicates worst health state.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in European Quality of Life (EuroQol) 5-Dimension, 5-Level (EQ 5D-5L) During OP/MA Phase: Sum Score	-0.7 Units on a Scale Standard Deviation 13.19

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study drug or 1 dose of oral AD in OP/MA phase.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in EQ-5D-5L Score During OP/MA Phase: EQ-VAS	1.6 Units on a Scale Standard Deviation 18.51

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study drug or 1 dose of oral AD in OP/MA phase.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline to Endpoint in EQ-5D-5L Scale Score During OP/MA Phase: Health Status Index	-0.009 Units on a Scale Standard Deviation 0.1411

SECONDARY outcome

Timeframe: Baseline (IND) up to the Endpoint (last post-baseline assessment value during 4 weeks of IND Phase)

SDS was a 5 item questionnaire used for assessment of functional impairment and associated disability. The first three items assess disruption of (1) work/school, (2) social life, (3) family life/home responsibilities using a 0 to 10 rating scale. Score for the first three items are summed to create a total score of 0 to 30, higher score indicates greater impairment and a negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=626 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Sheehan Disability Scale (SDS) Total Score During IND Phase	-9.3 Units on a Scale Standard Deviation 7.86

SECONDARY outcome

Timeframe: Baseline (OP/MA) up to the Endpoint (last post-baseline assessment value during 52 weeks of OP/MA phase)

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the OP/MA phase. Here, 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.

SDS was a participant-reported outcome measure and was a 5 item questionnaire used 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 to 10 rating scale. The score for the first three items are summed to create a total score of 0 to 30 where a higher score indicates greater impairment and a negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=541 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Change From Baseline in Sheehan Disability Scale Total Score During OP/MA Phase	-1.6 Units on a Scale Standard Deviation 8.25

SECONDARY outcome

Timeframe: Days 8, 15, 22 and Endpoint (last post-baseline assessment during 4 weeks of IND phase)

Population: The full (IND) analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the open-label IND phase (for direct-entry and transferred-entry non-responder participants). Here, 'n' signifies those participants who were evaluable at specific time point for this endpoint.

Response is defined as greater than or equal to (\>=) 50 % reduction from baseline in the MADRS total score. MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=779 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase Day 8	11.6 Percentage of participants
Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase Day 15	25.0 Percentage of participants
Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase Day 22	42.8 Percentage of participants
Percentage of Participants With Response as Assessed by MADRS Total Score During IND Phase End point	78.4 Percentage of participants

SECONDARY outcome

Timeframe: Day 15 and Endpoint (last post-baseline assessment value during 4 Week IND phase)

Response is defined as \>= 50 % reduction from baseline (IND phase) in PHQ-9 total score. PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. The scores are summed for a total score ranging from 0-27. A higher score indicates greater severity of depression. Severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=779 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Response as Assessed by PHQ-9 Total Score During IND Phase Day 15	37.2 Percentage of participants
Percentage of Participants With Response as Assessed by PHQ-9 Total Score During IND Phase End point	62.0 Percentage of participants

SECONDARY outcome

Timeframe: Days 8, 15, 22 and Endpoint (last post-baseline assessment value during 4 weeks of IND Phase)

Remission is defined as MADRS total score less than or equal to (\<=) 12. MADRS measures depression severity, detects changes due to AD treatment. It consists 10 items (evaluate apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, suicidal thoughts), scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), summed for a total possible score of 0 to 60. Higher scores indicate more severe condition. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=779 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase Day 8	7.3 Percentage of participants
Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase Day 15	15.6 Percentage of participants
Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase Day 22	27.2 Percentage of participants
Percentage of Participants With Remission as Assessed by MADRS Total Score During IND Phase End point	47.2 Percentage of participants

SECONDARY outcome

Timeframe: Day 15 and Endpoint (last post-baseline assessment value during 4 weeks of IND phase)

Remission is defined as PHQ-9 total score \<= 4. PHQ-9 is a 9-item, self-reporting scale assessing depressive symptoms. Each item was rated on a 4-point scale (0 = Not at all, 1 = Several Days, 2 = More than half the days, and 3 = Nearly every day), with a total score range of 0-27. The scores are summed for a total score ranging from 0-27. A higher score indicates greater severity of depression. severity of PHQ-9 categorized as follows: none-minimal (0-4), mild (5-9), moderate (10-14), moderately severe (15-19), severe (20-27). The recall period is 2 weeks. Negative change in score indicates improvement. Missing data was imputed using LOCF method and the last post baseline observation during the phase was carried forward as the "Endpoint".

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=779 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Remission as Assessed by PHQ-9 Total Score During IND Phase Day 15	12.7 Percentage of participants
Percentage of Participants With Remission as Assessed by PHQ-9 Total Score During IND Phase Endpoint	26.9 Percentage of participants

SECONDARY outcome

Timeframe: Predose, up to 1.5 hours postdose (up to end of IND phase [Week 4])

The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = "Not at all", 1 = "Mild", 2 = "Moderate", 3 = 'Severe" and 4 = "Extreme"). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=775 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With an Increase Score From Predose at Any Time in Clinician-Administered Dissociative States Scale (CADSS) Total Score During IND Phase	92.0 Percentage of participants

SECONDARY outcome

Timeframe: Predose, up to 1.5 hours postdose (up to end of OP/MA phase [Week 52])

Population: The full (OP/MA) analysis set included all participants who received at least 1 dose of intranasal study medication or 1 dose of oral antidepressant in the OP/MA phase.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=603 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With an Increase Score From Predose at Any Time in CADSS Total Score During OP/MA Phase	86.1 Percentage of participants

SECONDARY outcome

Timeframe: Up to End of OP/MA phase (Week 52)

Percentage of participants with treatment-emergent acute hypertension (Systolic Blood Pressure \>=180 millimeters of mercury \[mm Hg\] or Diastolic Blood Pressure \>= 110 mm Hg) during IND and OP/MA Phases were evaluated.

Outcome measures

Outcome measures
Measure	Intranasal Esketamine + Oral Antidepressant n=802 Participants Participants enrolled directly or TRD3005 non-responders self-administered intranasal Esketamine (Esk) twice a week for 4 weeks as age dependent flexible dose according to titration regimen for 56 or 84 milligram (mg) (\<65 years) and 28, 56 or 84 mg (\>=65 years) in IND phase. Participants who met response criteria at end of IND phase, entered OP/MA phase and received intranasal esketamine weekly from week 5-8 of OP/MA phase. From Week 9-52, participants received Esk either weekly or every other week based on MADRS score. TE (TRD3005 responders) joined OP/MA phase and received intranasal Esk 28, 56 or 84 mg weekly until week 8. DE participants initiated new oral antidepressant (AD) (1 of: duloxetine/escitalopram/sertraline/venlafaxine extended release \[XR\]) on Day 1 of IND phase and continued during IND and OP/MA phase. TE participants continued same oral AD from TRD3005. No intranasal Esk was given in follow-up phase and same oral AD was continued at investigator's clinical judgement.
Percentage of Participants With Treatment-Emergent Acute Hypertension (Systolic and Diastolic) During IND and OP/MA Phases Systolic BP >=180	2.2 Percentage of participants
Percentage of Participants With Treatment-Emergent Acute Hypertension (Systolic and Diastolic) During IND and OP/MA Phases Diastolic BP >=110	2.4 Percentage of participants
Percentage of Participants With Treatment-Emergent Acute Hypertension (Systolic and Diastolic) During IND and OP/MA Phases Acute hypertension	4.1 Percentage of participants

Adverse Events

IND: Intranasal Esketamine + Oral AD

Serious events: 17 serious events

Other events: 587 other events

Deaths: 0 deaths

OP/MA: Intranasal Esketamine + Oral AD

Serious events: 38 serious events

Other events: 454 other events

Deaths: 2 deaths

FU: Intranasal Esketamine + Oral AD

Serious events: 8 serious events

Other events: 24 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Director

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee A copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested in writing, such publication will be withheld for up to an additional 60 days.
Publication restrictions are in place

Restriction type: OTHER