54135419SUI3002: 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
Condition: Depressive Disorder, Major
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Suicide; Suicidal Ideation
Intervention: Esketamine; Placebo; Standard of Care
Intervention description: Participants will receive intranasal esketamine 84 milligram (mg) two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25).; Participants will receive intranasal placebo two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25).; The standard of care antidepressant treatment (antidepressant monotherapy or antidepressant plus augmentation therapy) will be determined by the treating physician(s) based on clinical judgement and practice guidelines prior to randomization, and the treatment will be initiated on Day 1.
Intervention MeSH terms: Esketamine
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 230.0
Sex: All
Minimum age: 18 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy of intranasal esketamine 84 milligram
      (mg) compared with intranasal placebo in addition to comprehensive standard of care in
      reducing the symptoms of Major Depressive Disorder (MDD), including suicidal ideation, in
      participants who are assessed to be at imminent risk for suicide, as measured by the change
      from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24
      hours post first dose.
    

Eligibility criteria:

        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