Trial Outcomes & Findings for A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression (NCT NCT04599855)

Last Updated: 2025-04-25

Results Overview

The MADRS was a clinician-rated scale designed to measure depression severity and detect changes due to antidepressant treatment. The scale consisted of 10 items, each of which was scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms). MADRS total score was the sum of scores from individual question items, which ranged from 0 to 60, higher scores represented a more severe condition. The MADRS evaluated apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, inability to feel (interest level), pessimistic thoughts, and suicidal thoughts. Negative change in MADRS total score indicated improvement.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

477 participants

Primary outcome timeframe

Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)

Results posted on

2025-04-25

Participant Flow

Adult participants with recurrent or single (duration greater than or equal to \[\>=\] 2 years) episode major depressive disorder (DSM-5 criteria) without psychotic features who experienced inadequate response (less than or equal to \[\<=\] 25 percent \[%\] improvement) to \>=2 oral antidepressants during the current depressive episode were randomized in the study.

Participant milestones

Participant milestones
Measure	Placebo In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the open-label (OL) phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 milligrams (mg) nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Esketamine 56 mg In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Esketamine 84 mg In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.
Double Blind Period (Day 1 to Day 28) STARTED	250	106	121
Double Blind Period (Day 1 to Day 28) Treated	250	105	121
Double Blind Period (Day 1 to Day 28) COMPLETED	238	101	107
Double Blind Period (Day 1 to Day 28) NOT COMPLETED	12	5	14
Period Title: OL Period (Week 5 to 16) STARTED	237	99	106
Period Title: OL Period (Week 5 to 16) Participants Who Entered OL Treatment Phase	237	99	105
Period Title: OL Period (Week 5 to 16) Participants Who Entered OL Observation Phase	0	0	1
Period Title: OL Period (Week 5 to 16) COMPLETED	204	87	95
Period Title: OL Period (Week 5 to 16) NOT COMPLETED	33	12	11

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the open-label (OL) phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 milligrams (mg) nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Esketamine 56 mg In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Esketamine 84 mg In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.
Double Blind Period (Day 1 to Day 28) Withdrawal by Subject	5	2	5
Double Blind Period (Day 1 to Day 28) Adverse Event	2	1	5
Double Blind Period (Day 1 to Day 28) Lack of Efficacy	2	0	2
Double Blind Period (Day 1 to Day 28) Protocol Violation	1	0	1
Double Blind Period (Day 1 to Day 28) Lost to Follow-up	0	1	0
Double Blind Period (Day 1 to Day 28) Pregnancy	1	0	0
Double Blind Period (Day 1 to Day 28) Other	1	0	1
Double Blind Period (Day 1 to Day 28) Randomized but not treated	0	1	0
Period Title: OL Period (Week 5 to 16) Withdrawal by Subject	8	5	6
Period Title: OL Period (Week 5 to 16) Lack of Efficacy	10	3	2
Period Title: OL Period (Week 5 to 16) Adverse Event	4	2	1
Period Title: OL Period (Week 5 to 16) Lost to Follow-up	4	1	2
Period Title: OL Period (Week 5 to 16) Protocol Violation	2	0	0
Period Title: OL Period (Week 5 to 16) Other	5	1	0

Baseline Characteristics

A Study of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants With Treatment-resistant Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Esketamine 56 mg n=105 Participants In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Esketamine 84 mg n=121 Participants In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the OL phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.	Total n=476 Participants Total of all reporting groups	Placebo n=250 Participants In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. After completion of the DB phase (including Day 28 visit), participants opted to enter the open-label (OL) phase (treatment/observation phase). Participants who opted OL treatment phase received esketamine 56 milligrams (mg) nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. Participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB or OL treatment phase.
Age, Categorical <=18 years	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	95 Participants n=7 Participants	107 Participants n=5 Participants	431 Participants n=4 Participants	229 Participants n=5 Participants
Age, Categorical >=65 years	10 Participants n=7 Participants	14 Participants n=5 Participants	45 Participants n=4 Participants	21 Participants n=5 Participants
Age, Continuous	45.1 Years STANDARD_DEVIATION 13.92 • n=7 Participants	45.1 Years STANDARD_DEVIATION 14.75 • n=5 Participants	45.3 Years STANDARD_DEVIATION 14.01 • n=4 Participants	45.4 Years STANDARD_DEVIATION 13.72 • n=5 Participants
Sex: Female, Male Female	60 Participants n=7 Participants	77 Participants n=5 Participants	284 Participants n=4 Participants	147 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=7 Participants	44 Participants n=5 Participants	192 Participants n=4 Participants	103 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=7 Participants	8 Participants n=5 Participants	42 Participants n=4 Participants	25 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	95 Participants n=7 Participants	112 Participants n=5 Participants	428 Participants n=4 Participants	221 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=7 Participants	1 Participants n=5 Participants	6 Participants n=4 Participants	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=7 Participants	5 Participants n=5 Participants	14 Participants n=4 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	7 Participants n=7 Participants	11 Participants n=5 Participants	35 Participants n=4 Participants	17 Participants n=5 Participants
Race (NIH/OMB) White	91 Participants n=7 Participants	102 Participants n=5 Participants	410 Participants n=4 Participants	217 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=7 Participants	0 Participants n=5 Participants	5 Participants n=4 Participants	4 Participants n=5 Participants
Region of Enrollment United States	105 Participants n=7 Participants	121 Participants n=5 Participants	476 Participants n=4 Participants	250 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1 (pre-randomization) to Day 28 (end of DB treatment phase)

Population: Full efficacy analysis set included all randomized participants who met nonresponse criteria and received at least 1 dose of DB study intervention. Here 'N' (overall number of participants analyzed) refers to the number of participants evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	DB: Placebo n=185 Participants In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.	DB: Esketamine 56 mg n=82 Participants In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.	DB: Esketamine 84 mg n=89 Participants In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.
Double-blind Treatment Phase: Change in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score From Day 1 (Pre-randomization) to Day 28	-7.0 Score on a scale Standard Deviation 10.07	-12.7 Score on a scale Standard Deviation 11.82	-13.9 Score on a scale Standard Deviation 11.89

SECONDARY outcome

Timeframe: Day 1 (pre-randomization) to Day 2 of DB treatment phase (24 hours post first dose on Day 1)

Outcome measures

Outcome measures
Measure	DB: Placebo n=195 Participants In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.	DB: Esketamine 56 mg n=84 Participants In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.	DB: Esketamine 84 mg n=93 Participants In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25. All participants underwent 1-week follow-up phase for safety assessment after their last dose of study treatment in DB phase.
Double-blind Treatment Phase: Change in MADRS Total Score From Day 1 (Pre-randomization) to Day 2 (24 Hours Post First Dose on Day 1)	-9.7 Score on a scale Standard Deviation 10.27	-13.9 Score on a scale Standard Deviation 10.15	-13.0 Score on a scale Standard Deviation 9.68

Adverse Events

DB: Placebo

Serious events: 3 serious events

Other events: 73 other events

Deaths: 0 deaths

DB: Esketamine 56 mg

Serious events: 1 serious events

Other events: 69 other events

Deaths: 0 deaths

DB: Esketamine 84 mg

Serious events: 2 serious events

Other events: 80 other events

Deaths: 0 deaths

OL Treatment: Placebo to Esketamine

Serious events: 6 serious events

Other events: 147 other events

Deaths: 0 deaths

OL Treatment: Esketamine 56 mg to Esketamine

Serious events: 3 serious events

Other events: 49 other events

Deaths: 0 deaths

OL Treatment: Esketamine 84 mg to Esketamine

Serious events: 0 serious events

Other events: 44 other events

Deaths: 0 deaths

OL Observation Period

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Follow up: All Participants

Serious events: 1 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	DB: Placebo n=250 participants at risk In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	DB: Esketamine 56 mg n=105 participants at risk In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	DB: Esketamine 84 mg n=121 participants at risk In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	OL Treatment: Placebo to Esketamine n=237 participants at risk Participants who received placebo in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Treatment: Esketamine 56 mg to Esketamine n=99 participants at risk Participants who received esketamine 56 mg in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Treatment: Esketamine 84 mg to Esketamine n=105 participants at risk Participants who received esketamine 84 mg in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Observation Period n=1 participants at risk After completion of DB treatment phase, participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression.	Follow up: All Participants n=476 participants at risk Participants who received at least 1 dose of study treatment in the DB or OL treatment phase entered into 1- week follow-up phase after their last dose of study treatment.
Cardiac disorders Acute Myocardial Infarction	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Gastrointestinal disorders Abdominal Hernia Obstructive	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.0% 1/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Gastrointestinal disorders Constipation	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 1/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Gastrointestinal disorders Vomiting	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 1/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Infections and infestations Peritonitis	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.0% 1/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Injury, poisoning and procedural complications Ankle Fracture	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.95% 1/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Injury, poisoning and procedural complications Hip Fracture	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.21% 1/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.84% 2/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Ophthalmic Migraine	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.83% 1/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Colon Cancer	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 1/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial Cancer	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.0% 1/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Loss of Consciousness	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 1/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Syncope	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 1/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Self-Injurious Ideation	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Suicidal Ideation	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Suicide Attempt	0.00% 0/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.83% 1/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.

Other adverse events

Other adverse events
Measure	DB: Placebo n=250 participants at risk In the double-blind (DB) phase, participants received placebo nasal spray (matching to esketamine) twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	DB: Esketamine 56 mg n=105 participants at risk In the DB phase, participants received esketamine 56 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	DB: Esketamine 84 mg n=121 participants at risk In the DB phase, participants received esketamine 84 mg nasal spray twice a week for 4 weeks on Days 1, 4, 8, 11, 15, 18, 22, and 25.	OL Treatment: Placebo to Esketamine n=237 participants at risk Participants who received placebo in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Treatment: Esketamine 56 mg to Esketamine n=99 participants at risk Participants who received esketamine 56 mg in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Treatment: Esketamine 84 mg to Esketamine n=105 participants at risk Participants who received esketamine 84 mg in DB phase were given a choice either to receive esketamine nasal spray treatment or were observed only without nasal spray treatment. Participants who opted OL treatment phase received esketamine 56 mg nasal spray on Day 28 regardless of the treatment assignment in the DB phase and received subsequent doses at the same or adjusted (56 mg or 84 mg) dose level based on efficacy and tolerability with dosing frequency: twice weekly from Weeks 5 to 8 followed by once weekly from Weeks 9 to 12 and then weekly or every other week from Weeks 13 to 16 based on clinical judgment and was individualized to the least frequent dosing to maintain remission/response. During this period participants were given the option to receive standard-of-care treatment for depression. As planned, OL phase adverse events analysis was performed by treatment groups assigned in the DB phase, irrespective of the OL phase adjusted doses.	OL Observation Period n=1 participants at risk After completion of DB treatment phase, participants who opted OL observation phase were only observed without esketamine nasal spray treatment but received standard-of-care treatment for depression.	Follow up: All Participants n=476 participants at risk Participants who received at least 1 dose of study treatment in the DB or OL treatment phase entered into 1- week follow-up phase after their last dose of study treatment.
Gastrointestinal disorders Diarrhoea	2.4% 6/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.9% 3/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.83% 1/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.8% 16/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.1% 5/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.9% 3/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.21% 1/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Gastrointestinal disorders Nausea	8.4% 21/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	22.9% 24/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	26.4% 32/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	29.1% 69/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	18.2% 18/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	14.3% 15/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Gastrointestinal disorders Vomiting	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.8% 5/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	8.3% 10/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	11.4% 27/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.1% 6/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.9% 2/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.21% 1/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
General disorders Fatigue	4.4% 11/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	7.6% 8/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.8% 7/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	7.6% 18/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.1% 6/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.8% 5/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
General disorders Feeling Drunk	0.80% 2/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	7.6% 8/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.6% 8/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.5% 13/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.1% 6/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.7% 6/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Infections and infestations Upper Respiratory Tract Infection	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.95% 1/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.7% 2/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.1% 12/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.95% 1/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.84% 4/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Dizziness	7.2% 18/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	21.0% 22/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	22.3% 27/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	19.0% 45/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	8.1% 8/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	9.5% 10/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.21% 1/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Dysgeusia	3.6% 9/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.8% 5/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.1% 5/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.9% 14/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.0% 4/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.8% 5/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Headache	8.8% 22/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	18.1% 19/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	19.8% 24/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	15.2% 36/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	13.1% 13/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	10.5% 11/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.42% 2/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Hypoaesthesia	0.40% 1/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.9% 2/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.1% 5/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	6.3% 15/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.0% 2/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.8% 4/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Nervous system disorders Somnolence	1.6% 4/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.7% 6/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.5% 3/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.2% 10/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.0% 2/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.9% 2/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Anxiety	1.2% 3/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.8% 5/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	8.3% 10/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.9% 14/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.0% 3/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.8% 4/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Dissociation	2.8% 7/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	21.9% 23/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	26.4% 32/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	17.7% 42/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	12.1% 12/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	14.3% 15/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Psychiatric disorders Insomnia	3.6% 9/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.7% 6/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	4.1% 5/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.8% 9/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.0% 2/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.95% 1/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.
Respiratory, thoracic and mediastinal disorders Throat Irritation	0.80% 2/250 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.8% 4/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	3.3% 4/121 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	5.5% 13/237 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	2.0% 2/99 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	1.9% 2/105 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/1 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.	0.00% 0/476 • Double-blind (DB) phase: From Day 1 (post-dose) to Day 28; Open-label (OL) phase: From Week 5 to Week 16; Follow-up (FU) phase: Up to 1 week after last dose of study drug in DB phase (Week 5) or OL treatment phase (Week 17) All cause mortality:Randomized analysis set:all randomized participants; serious adverse events (AE)/other AE:DB:Safety analysis set(SAS):all randomized participants who received at least 1 dose of DB intervention; OL arms:OL analysis set:all participants who received at least 1 dose of OL esketamine; OL observation arm:Observation analysis set:all participants who entered observation phase but did not receive OL esketamine; FU:SAS. FU:All Participants arm: combined data of DB and OL per plan.

Additional Information

Global Medical Head

Janssen Research & Development, LLC

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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 to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER