A Study of the Efficacy and Safety of Intranasal Esketamine in the Rapid Reduction of Symptoms of Major Depressive Disorder, in Adult at Imminent Risk for Suicide

This is a randomized (study medication assigned to participants by chance), double-blind
(neither the researchers nor the participants know what treatment the participant is
receiving), placebo-controlled (an inactive substance which contains no drug) that is
compared in a clinical trial with a drug to test if the drug has a real effect), multicenter
(when more than one hospital or study team work on a medical research study) study. Study
will enroll participants with suicidal ideation who are assessed to be at imminent risk for
suicide. The study will consist of a screening evaluation performed within 48 hours prior to
the Day 1 intranasal dose immediately followed by a 25-day double-blind treatment phase (Day
1 to 25), and a 65 day follow-up phase (Day 26 to Day 90). The total study duration for each
subject will be approximately 13 weeks. Participants' safety will be evaluated throughout the
study. If you or a loved one are having thoughts of suicide, please seek immediate medical
help. Go to the emergency room or call the National Suicide Prevention Lifeline at
1-800-273-8255.

Inclusion Criteria:

- Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th
edition) (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without
psychotic features, based upon clinical assessment and confirmed by the Mini
International Psychiatric Interview (MINI)

- In the physician's opinion, acute psychiatric hospitalization is clinically warranted
due to participant's imminent risk of suicide

- Participants must have current suicidal ideation with intent, confirmed by a "Yes"
response to Question B3 [Think (even momentarily) about harming or of hurting or of
injuring yourself: with at least some intent or awareness that you might die as a
result; or think about suicide (ie, about killing yourself)?] and Question B10 [Intend
to act on thoughts of killing yourself?] obtained from the MINI. Note: the response to
B3 must refer to the present, whereas the response to B10 may reflect the past 24
hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of
MINI must be repeated prior to randomization to confirm eligibility

- Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of
greater than (>) 28 predose on Day 1

- As part of standard of care treatment, participant agrees to be hospitalized
voluntarily for a recommended period of 5 days after randomization (may be shorter or
longer if clinically warranted in the investigator's opinion) and take prescribed
non-investigational antidepressant therapy(ies) for at least the duration of the
double-blind treatment phase (Day 25)

- Participant is comfortable with self-administration of intranasal medication and able
to follow instructions provided

Exclusion Criteria:

- Participant has a current DSM-5 diagnosis of bipolar (or related disorders),
antisocial personality disorder, or obsessive compulsive disorder

- Participant currently meets DSM-5 criteria for borderline personality disorder.
Participant not meeting full DSM-5 criteria for borderline personality disorder but
exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should
also be excluded

- Participant has a current clinical diagnosis of autism, dementia, or intellectual
disability

- Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD
with psychotic features

- Participant meets the DSM-5 severity criteria for moderate or severe substance or
alcohol use disorder, (except for nicotine or caffeine), within the 6 months before
screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid
diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related
use disorder is exclusionary