A Study to Evaluate the Efficacy and Safety of Intranasal Esketamine in Addition to Comprehensive Standard of Care for the Rapid Reduction of the Symptoms of Major Depressive Disorder, Including Suicidal Ideation, in Adult Participants Assessed to be at Imminent Risk for Suicide

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)

- 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

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

- 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 14 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)

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. Note:
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 12 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

- Participant has a history or current signs and symptoms of liver or renal
insufficiency, clinically significant cardiac (including unstable coronary artery
disease and congestive heart failure, tachyarrhythmias and recent myocardial
infarction) or vascular, pulmonary, gastrointestinal, endocrine (including
uncontrolled hyperthyroidism), neurologic (including current or past history of
seizures except uncomplicated childhood febrile seizures with no sequelae),
hematologic, rheumatologic, or metabolic (including severe dehydration/ hypovolemia)
disease

- Participant has known allergies, hypersensitivity, intolerance or contraindications to
esketamine or ketamine or its excipients