<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03039192</url>
  </required_header>
  <id_info>
    <org_study_id>CR108284</org_study_id>
    <secondary_id>2016-003990-17</secondary_id>
    <secondary_id>54135419SUI3001</secondary_id>
    <nct_id>NCT03039192</nct_id>
  </id_info>
  <brief_title>54135419SUI3001: 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</brief_title>
  <acronym>Aspire I</acronym>
  <official_title>A Double-blind, Randomized, Placebo-controlled 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 Subjects Assessed to be at Imminent Risk for Suicide</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of the study is to evaluate the efficacy of intranasal esketamine 84 milligram&#xD;
      (mg) compared with intranasal placebo in addition to comprehensive standard of care in&#xD;
      reducing the symptoms of Major Depressive Disorder (MDD), including suicidal ideation, in&#xD;
      participants who are assessed to be at imminent risk for suicide, as measured by the change&#xD;
      from baseline on the Montgomery-Asberg Depression Rating Scale (MADRS) total score at 24&#xD;
      hours post first dose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized (study medication assigned to participants by chance), double-blind&#xD;
      (neither the researchers nor the participants know what treatment the participant is&#xD;
      receiving), placebo-controlled (an inactive substance which contains no drug) that is&#xD;
      compared in a clinical trial with a drug to test if the drug has a real effect), multicenter&#xD;
      (when more than one hospital or study team work on a medical research study) study. Study&#xD;
      will enroll participants with suicidal ideation who are assessed to be at imminent risk for&#xD;
      suicide. The study will consist of a screening evaluation performed within 48 hours prior to&#xD;
      the Day 1 intranasal dose immediately followed by a 25-day double-blind treatment phase (Day&#xD;
      1 to 25), and a 65 day follow-up phase (Day 26 to Day 90). The total study duration for each&#xD;
      subject will be approximately 13 weeks. Participants' safety will be evaluated throughout the&#xD;
      study. If you or a loved one are having thoughts of suicide, please seek immediate medical&#xD;
      help. Go to the emergency room or call the National Suicide Prevention Lifeline at&#xD;
      1-800-273-8255.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 9, 2017</start_date>
  <completion_date type="Actual">December 18, 2018</completion_date>
  <primary_completion_date type="Actual">December 18, 2018</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase</measure>
    <time_frame>Baseline (Day 1, predose) and 24 hours first post dose (Day 2)</time_frame>
    <description>MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase</measure>
    <time_frame>Baseline (Day 1, predose) and 24 hours first post dose (Day 2)</time_frame>
    <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [&lt;=] 12) Through the Double-blind Phase</measure>
    <time_frame>Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25 (predose and 4 hours postdose)</time_frame>
    <description>Participants who had a MADRS total score of &lt;=12 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)</time_frame>
    <description>MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase</measure>
    <time_frame>Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline, Days 8 and 25</time_frame>
    <description>BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index</measure>
    <time_frame>Baseline and Days 2, 11 and 25</time_frame>
    <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS)</measure>
    <time_frame>Baseline, Days 2, 11 and 25</time_frame>
    <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score from 0 (worst health) to 100 (best health), positive change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score</measure>
    <time_frame>Baseline, Days 2, 11 and 25</time_frame>
    <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L system and EQ-VAS. EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, and Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health), a lower score indicates worse health. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Sum score ranges from 0-100. Higher score indicates a more severe problem. Negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline and Days 2, 11 and 25</time_frame>
    <description>The QLDS is a disease specific patient-reported outcome designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of &quot;at the moment&quot;, contains 34-items with &quot;true&quot;/&quot;not true&quot; response options and takes approximately 5-10 minutes to complete. The total score range is from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase</measure>
    <time_frame>Days 15 and 25</time_frame>
    <description>The TSQM-9 is a 9-item generic patient-reported outcome instrument to assess participants' satisfaction with medication. It covers domains of effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores were calculated as recommended by the instrument authors. (i) Effectiveness = [(item 1 + item 2 + item 3) - 3]/18*100, (ii) Convenience = [(item 4 + item 5 + item 6) - 3]/18*100 and (iii) Global satisfaction = [(item 7 + item 8 + item 9) - 3]/14*100. Each domain score can be calculated only if all the three items considered in the calculation of that score are not missing. The TSQM-9 domain score ranges from 0 to 100, with higher scores representing higher satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline, Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>SIBAT is an assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT is organized into 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Patient-reported section has modules of demographics and suicide history, risk/protective factors, suicidal thinking, suicide behavior, and suicide risk. Question 3 from Module 5 asks participants to describe their thinking about suicide right now from 5 response options ranging from 0 (I have no suicidal thoughts) to 4 (I have suicidal thoughts all of time). SIBAT Module 5 (My Risk) Question 3 (Patient-reported FoST) total score ranges from 0 to 4; a higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 - Clinician-rated FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</measure>
    <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>SIBAT is assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT has 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Clinician-rated section has modules for semi-structured interview, clinical global impressions of current severity of suicidality and imminent suicide risk, clinical global impression of long-term suicide risk, and clinical judgment of optimal suicide management. The score anchor point as in participant report frequency of suicidal thinking (FoST) that is, response options from never to all the time. Module 7-FoST score ranges from 0-5; higher score indicates more severe condition. Negative change in score indicates improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to study agent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>Low/high abnormal values are: Alanine aminotransferase (ALT)-high=200 Units per liter(U/L); ALP-high=250U/L; aspartate aminotransferase(AST)-high=250U/L; gamma glutamyl transferase(GGT)=300U/L; Albumin(low=24g/L,high=60 g/L); Bicarbonate(low=15.1, high=34.9mmol/L); Bilirubin(high=51.3micromol/L); calcium(low=1.5,high=3mmol/L);Chloride(low=94,high=112mmol/L); CK(High=990U/L); Creatinine(High=265.2micromol/L); Eosinophils(High=10%); Erythrocytes(low=3.0*1012/L,high=6.4*1012/L); Glucose(low=2.2,high=16.7mmol/L); Hemoglobin(low=80g/L,high=190g/L);Hematocrit(low=0.28, high=0.55 fraction); LD(high=500U/L); Leukocytes(low=2.5*109/L,high=15.5*109/L); Lymphocytes(low=10%,high=60%); Monocytes(high=20%); Neutrophils(low=30%,high=90%); Phosphate(low=0.7 mmol/L,high=2.6mmol/L); Platelet count(low=100*109/L,high=600*109/L]; Potassium(low=3.0mmol/L,high=5.8 mmol/L]; Protein(low=50 g/L); Sodium(low=125 mmol/L,high=155 mmol/L); Urate(low=89.2 micromol/L,high=594.8micromol/L); Urine(high=8.0 pH).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase</measure>
    <time_frame>At Day 25</time_frame>
    <description>Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>Number of participants with treatment emergent abnormal ECG values for variables including heart rate (abnormally low refers to less than or equal to [&lt;=] 50 beats per minute [bpm] , abnormally high refers greater than or equal to [&gt;=] 100 bpm), pulse rate (PR) interval (abnormally high refers to &gt;= 210 milliseconds [msec]), QRS interval (abnormally Low refers to &lt;= 50, abnormally high refers to &gt;= 120 msec) and QT interval (abnormally low refers to &lt;= 200, abnormally high &gt;= 500 msec) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [&lt;] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>Pulse oximetry was used to measure arterial SpO2 levels. On each dosing day, the device was attached to the finger, toe, or ear, and SpO2 was monitored and documented. If oxygen saturation levels were less than (&lt;) 93% at any time during the 1.5 hours postdose interval, pulse oximetry was recorded every 5 minutes until levels return to &gt;= 93% or until the participant is referred for appropriate medical care, if clinically indicated. Participants with at least 2 consecutive postdose oxygen saturation below 93% during the DB treatment phase were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>Number of participants with treatment emergent vital signs abnormalities (pulse rate in bpm [abnormally low = a decrease from baseline of &gt;= 15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;=15 to a value &gt;=100] , systolic blood pressure [SBP] in mmHg [abnormally low = a decrease from baseline of &gt;= 20 to a value &lt;= 90; abnormally high = an increase from baseline of &gt;= 20 to a value &gt;= 180], and diastolic blood pressure [DBP] in mmHg [abnormally low= a decrease from baseline of &gt;=15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;= 15 to a value &gt;= 105) were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase</measure>
    <time_frame>Up to Day 25</time_frame>
    <description>MOAA/S was used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American society of anesthesiologists (ASA) continuum. The MOAA/S scores range from 0 to 5 where,0 = no response to painful stimulus; ASA continuum = general anesthesia, 1 = responds to trapezius squeeze; ASA continuum = deep sedation, 2 = purposeful response to mild prodding or mild shaking; ASA continuum = moderate sedation, 3 = responds after name called loudly or repeatedly; ASA continuum = moderate sedation, 4 = lethargic response to name spoken in normal tone; ASA continuum = moderate sedation and 5 = readily responds to name spoken in normal tone (awake); ASA continuum = minimal sedation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase</measure>
    <time_frame>Days 1, 4, 8, 11, 15, 18, 22 and 25</time_frame>
    <description>The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = &quot;Not at all&quot;, 1 = &quot;Mild&quot;, 2 = &quot;Moderate&quot;, 3 = 'Severe&quot; and 4 = &quot;Extreme&quot;). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition. Number of participants with an increase in CADSS total score (increase based on maximum CADSS total score change from predose of &gt; 0) was reported.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">226</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Esketamine + Standard of care</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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) along with standard of care (SOC) antidepressant treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo + Standard of care</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive intranasal placebo two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) along with standard of care antidepressant treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Esketamine</intervention_name>
    <description>Intranasal esketamine solution 84 milligram (mg)</description>
    <arm_group_label>Esketamine + Standard of care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Intranasal Placebo solution</description>
    <arm_group_label>Placebo + Standard of care</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of Care</intervention_name>
    <description>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.</description>
    <arm_group_label>Esketamine + Standard of care</arm_group_label>
    <arm_group_label>Placebo + Standard of care</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must meet Diagnostic and Statistical Manual of Mental Disorders (5th&#xD;
             edition) (DSM-5) diagnostic criteria for Major Depressive Disorder (MDD), without&#xD;
             psychotic features, based upon clinical assessment and confirmed by the Mini&#xD;
             International Psychiatric Interview (MINI)&#xD;
&#xD;
          -  In the physician's opinion, acute psychiatric hospitalization is clinically warranted&#xD;
             due to participant's imminent risk of suicide&#xD;
&#xD;
          -  Participants must have current suicidal ideation with intent, confirmed by a &quot;Yes&quot;&#xD;
             response to Question B3 [Think (even momentarily) about harming or of hurting or of&#xD;
             injuring yourself: with at least some intent or awareness that you might die as a&#xD;
             result; or think about suicide (ie, about killing yourself)?] and Question B10 [Intend&#xD;
             to act on thoughts of killing yourself?] obtained from the MINI. Note: the response to&#xD;
             B3 must refer to the present, whereas the response to B10 may reflect the past 24&#xD;
             hours. If the screening period is longer than 24 hours, assessment of B3 and B10 of&#xD;
             MINI must be repeated prior to randomization to confirm eligibility&#xD;
&#xD;
          -  Participant has a Montgomery Asberg Depression Rating Scale (MADRS) total score of&#xD;
             greater than (&gt;) 28 predose on Day 1&#xD;
&#xD;
          -  As part of standard of care treatment, participant agrees to be hospitalized&#xD;
             voluntarily for a recommended period of 5 days after randomization (may be shorter or&#xD;
             longer if clinically warranted in the investigator's opinion) and take prescribed&#xD;
             non-investigational antidepressant therapy(ies) for at least the duration of the&#xD;
             double-blind treatment phase (Day 25)&#xD;
&#xD;
          -  Participant is comfortable with self-administration of intranasal medication and able&#xD;
             to follow instructions provided&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participant has a current DSM-5 diagnosis of bipolar (or related disorders),&#xD;
             antisocial personality disorder, or obsessive compulsive disorder&#xD;
&#xD;
          -  Participant currently meets DSM-5 criteria for borderline personality disorder.&#xD;
             Participant not meeting full DSM-5 criteria for borderline personality disorder but&#xD;
             exhibiting recurrent suicidal gestures, threats, or self-mutilating behaviors should&#xD;
             also be excluded&#xD;
&#xD;
          -  Participant has a current clinical diagnosis of autism, dementia, or intellectual&#xD;
             disability&#xD;
&#xD;
          -  Participant has a current or prior DSM-5 diagnosis of a psychotic disorder, or MDD&#xD;
             with psychotic features&#xD;
&#xD;
          -  Participant meets the DSM-5 severity criteria for moderate or severe substance or&#xD;
             alcohol use disorder, (except for nicotine or caffeine), within the 6 months before&#xD;
             screening. A history (lifetime) of ketamine, phencyclidine (PCP), lysergic acid&#xD;
             diethylamide (LSD), or 3, 4-methylenedioxy-methamphetamine (MDMA) hallucinogen-related&#xD;
             use disorder is exclusionary&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UAB Department of Psychiatry and Behavioral Neurobiology</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metropolitan Neuro Behavioral Institute</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <zip>85226</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Collaborative NeuroScience Network</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06511</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rush University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alexian Behavioral Health Hospital</name>
      <address>
        <city>Hoffman Estates</city>
        <state>Illinois</state>
        <zip>60169</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Louisville, Department of Psychiatry</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LSU Health Sciences Center New Orleans</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louisiana Clinical Research</name>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71101</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheppard Pratt Health System</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CBH Health</name>
      <address>
        <city>Gaithersburg</city>
        <state>Maryland</state>
        <zip>20877</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State University of New York</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trials of America</name>
      <address>
        <city>Hickory</city>
        <state>North Carolina</state>
        <zip>28601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mental Health Center Prof. Dr. Ivan Temkov</name>
      <address>
        <city>Bourgas</city>
        <zip>8001</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional Psychiatric Dispansery</name>
      <address>
        <city>Bulgaria</city>
        <zip>7003</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>State Psychiatric Hospital - Lovech</name>
      <address>
        <city>Lovech</city>
        <zip>5500</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT 'Sveti Georgi'-Plovdiv</name>
      <address>
        <city>Plovdiv</city>
        <zip>4002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Military Medical Academy, Multiprofile Hospital for Active Treatment -Sofia</name>
      <address>
        <city>Sofia</city>
        <zip>1606</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Estonian Medical Centre Foundation</name>
      <address>
        <city>Tallinn</city>
        <zip>10614</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tartu University Hospital</name>
      <address>
        <city>Tartu</city>
        <zip>50417</zip>
        <country>Estonia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vivantes Humboldt Klinikum</name>
      <address>
        <city>Berlin</city>
        <zip>13509</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Frankfurt</name>
      <address>
        <city>Frankfurt Am Main</city>
        <zip>60528</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinik für Psychiatrie und Psychotherapie</name>
      <address>
        <city>Freiburg</city>
        <zip>79104</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Semmelweis Egyetem Kútvölgyi Klinikai Tömb</name>
      <address>
        <city>Budapest</city>
        <zip>1125</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Szent János Kórház és Észak-budai Egyesített Kórházak</name>
      <address>
        <city>Budapest</city>
        <zip>1125</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nyírő Gyula Kórház</name>
      <address>
        <city>Budapest</city>
        <zip>1135</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Petz Aladar Megyei Oktato Korhaz</name>
      <address>
        <city>Gyor</city>
        <zip>H-9024</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pecsi Tudomanyegyetem Klinikai Kozpont</name>
      <address>
        <city>Pecs</city>
        <zip>7623</zip>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Ansan Hospital</name>
      <address>
        <city>Ansan-si</city>
        <zip>15355</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chonnam National University Hospital</name>
      <address>
        <city>Gwangju-si</city>
        <zip>61469</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kyung Hee University Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>02447</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>3080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Kebangsaan Malaysia Medical Centre</name>
      <address>
        <city>Cheras</city>
        <zip>56000</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Kuala Lumpur</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>50586</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Malaya Medical Centre</name>
      <address>
        <city>Kuala Lumpur</city>
        <zip>59100</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Tuanku Jaafar</name>
      <address>
        <city>Seremban</city>
        <zip>70300</zip>
        <country>Malaysia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultna nemocnica s poliklinikou v Ziline</name>
      <address>
        <city>Zilina</city>
        <zip>012 07</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Flexivest 14 Research</name>
      <address>
        <city>Cape Town</city>
        <zip>7550</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juan Schrönen - Western Cape South Africa</name>
      <address>
        <city>Welgemoed</city>
        <zip>7530</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Fundacion Alcorcon</name>
      <address>
        <city>Alcorcón</city>
        <zip>28922</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Vall D'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Clinic I Provincial de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Inst. Internac. Neurociencias Aplicadas</name>
      <address>
        <city>Barcelona</city>
        <zip>8006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. de Basurto</name>
      <address>
        <city>Bilbao</city>
        <zip>48013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hosp. Univ. Ramon Y Cajal</name>
      <address>
        <city>Madrid</city>
        <zip>28034</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Univ. de Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Benito Menni Comp. Asist. Salut Mental</name>
      <address>
        <city>Sant Boi de Llobregat</city>
        <zip>08830</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tri-Service Genaral Hospital</name>
      <address>
        <city>Neihu District</city>
        <zip>114</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Medical University Shuang Ho Hospital</name>
      <address>
        <city>New Taipei City</city>
        <zip>23561</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chung Shan Medical University Hospital</name>
      <address>
        <city>Taichung</city>
        <zip>40201</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Estonia</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Korea, Republic of</country>
    <country>Malaysia</country>
    <country>Slovakia</country>
    <country>South Africa</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&amp;parentIdentifier=CR108284&amp;attachmentIdentifier=0b008702-9e7b-4d11-b853-d3aba96bb3a1&amp;fileName=54135419SUI3001_(CR108284)_Additional_Results_Data_CH.pdf&amp;versionIdentifier=</url>
    <description>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 (Aspire I)</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 31, 2017</study_first_submitted>
  <study_first_submitted_qc>January 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <results_first_submitted>September 1, 2020</results_first_submitted>
  <results_first_submitted_qc>October 8, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">October 29, 2020</results_first_posted>
  <disposition_first_submitted>December 16, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>October 8, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 29, 2020</disposition_first_posted>
  <last_update_submitted>October 8, 2020</last_update_submitted>
  <last_update_submitted_qc>October 8, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
    <mesh_term>Suicide</mesh_term>
    <mesh_term>Suicidal Ideation</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Esketamine</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03039192/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 2, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/92/NCT03039192/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo Plus SOC Antidepressant Treatment</title>
          <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
        </group>
        <group group_id="P2">
          <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
          <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
                <participants group_id="P2" count="114"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Treated</title>
              <participants_list>
                <participants group_id="P1" count="112"/>
                <participants group_id="P2" count="113"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="84"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="32"/>
                <participants group_id="P2" count="30"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse event, serious fatal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse event, non-fatal</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Discontinued from treatment phase</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set included all randomized participants who received at least 1 dose of study agent in the double-blind treatment phase.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo Plus SOC Antidepressant Treatment</title>
          <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
        </group>
        <group group_id="B2">
          <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
          <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="112"/>
            <count group_id="B2" value="113"/>
            <count group_id="B3" value="225"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.9" spread="12.54"/>
                    <measurement group_id="B2" value="40.8" spread="13.11"/>
                    <measurement group_id="B3" value="39.3" spread="12.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="139"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>More than one race</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="77"/>
                    <measurement group_id="B3" value="151"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>BULGARIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ESTONIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GERMANY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>HUNGARY</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MALAYSIA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SOUTH AFRICA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SOUTH KOREA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SPAIN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TAIWAN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>UNITED STATES</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase</title>
        <description>MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.</description>
        <time_frame>Baseline (Day 1, predose) and 24 hours first post dose (Day 2)</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a postbaseline evaluation for MADRS total score or CGI-SS-R. Here, N (number of participants analyzed) signifies number of participants analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase</title>
          <description>MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a postbaseline evaluation for MADRS total score or CGI-SS-R. Here, N (number of participants analyzed) signifies number of participants analyzed for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.8" spread="10.73"/>
                    <measurement group_id="O2" value="-16.4" spread="11.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.006</p_value>
            <method>ANCOVA</method>
            <param_type>Difference of Least Square Means</param_type>
            <param_value>-3.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.39</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.56</ci_lower_limit>
            <ci_upper_limit>-1.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase</title>
        <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).</description>
        <time_frame>Baseline (Day 1, predose) and 24 hours first post dose (Day 2)</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a postbaseline evaluation for MADRS total score or CGI-SS-R. Here, N (number of participants analyzed) signifies number of participants analyzed for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase</title>
          <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a postbaseline evaluation for MADRS total score or CGI-SS-R. Here, N (number of participants analyzed) signifies number of participants analyzed for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="111"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-6" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [&lt;=] 12) Through the Double-blind Phase</title>
        <description>Participants who had a MADRS total score of &lt;=12 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
        <time_frame>Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25 (predose and 4 hours postdose)</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during the double-blind phase and have had both a baseline and a post-baseline evaluation for the MADRS total score or CGI-SS-R.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [&lt;=] 12) Through the Double-blind Phase</title>
          <description>Participants who had a MADRS total score of &lt;=12 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during the double-blind phase and have had both a baseline and a post-baseline evaluation for the MADRS total score or CGI-SS-R.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1 (4 Hours postdose)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                    <measurement group_id="O2" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="30"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 25 (Predose)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38"/>
                    <measurement group_id="O2" value="46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 25 (4 hours postdose)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
        <description>MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
        <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
          <description>MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10.9" spread="9.69"/>
                    <measurement group_id="O2" value="-13.5" spread="10.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                    <count group_id="O2" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.9" spread="10.72"/>
                    <measurement group_id="O2" value="-16.4" spread="11.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.5" spread="11.39"/>
                    <measurement group_id="O2" value="-19.1" spread="12.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.4" spread="12.59"/>
                    <measurement group_id="O2" value="-19.7" spread="12.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-19.0" spread="12.08"/>
                    <measurement group_id="O2" value="-21.8" spread="12.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.4" spread="12.19"/>
                    <measurement group_id="O2" value="-22.3" spread="11.70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.4" spread="12.00"/>
                    <measurement group_id="O2" value="-23.9" spread="11.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.6" spread="12.32"/>
                    <measurement group_id="O2" value="-24.0" spread="12.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25: predose</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.0" spread="12.41"/>
                    <measurement group_id="O2" value="-24.8" spread="13.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25 (4 hours postdose)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="88"/>
                    <count group_id="O2" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-25.8" spread="10.94"/>
                    <measurement group_id="O2" value="-29.5" spread="10.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
        <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
        <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
          <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-6" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-6" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="0"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="0"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-5" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" lower_limit="-5" upper_limit="0"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase</title>
        <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).</description>
        <time_frame>Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during the double-blind phase and have had both a baseline and a post-baseline evaluation for the MADRS total score or CGI-SS-R.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase</title>
          <description>CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during the double-blind phase and have had both a baseline and a post-baseline evaluation for the MADRS total score or CGI-SS-R.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                    <measurement group_id="O2" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39"/>
                    <measurement group_id="O2" value="42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45"/>
                    <measurement group_id="O2" value="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                    <measurement group_id="O2" value="53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46"/>
                    <measurement group_id="O2" value="60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 18</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55"/>
                    <measurement group_id="O2" value="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 22</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 25</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57"/>
                    <measurement group_id="O2" value="71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
        <description>The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
        <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
          <description>The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-4" upper_limit="2"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-5" upper_limit="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-6" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase</title>
        <description>BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.</description>
        <time_frame>Baseline, Days 8 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase</title>
          <description>BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.4" spread="6.03"/>
                    <measurement group_id="O2" value="-5.3" spread="6.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="98"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.6" spread="6.63"/>
                    <measurement group_id="O2" value="-6.9" spread="6.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index</title>
        <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicates improvement.</description>
        <time_frame>Baseline and Days 2, 11 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index</title>
          <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.096" spread="0.1785"/>
                    <measurement group_id="O2" value="0.156" spread="0.1944"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.169" spread="0.2139"/>
                    <measurement group_id="O2" value="0.206" spread="0.2043"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.189" spread="0.2336"/>
                    <measurement group_id="O2" value="0.227" spread="0.2078"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS)</title>
        <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score from 0 (worst health) to 100 (best health), positive change in score indicates improvement.</description>
        <time_frame>Baseline, Days 2, 11 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS)</title>
          <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score from 0 (worst health) to 100 (best health), positive change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.8" spread="17.32"/>
                    <measurement group_id="O2" value="13.5" spread="20.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.3" spread="22.27"/>
                    <measurement group_id="O2" value="17.9" spread="24.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" spread="23.49"/>
                    <measurement group_id="O2" value="21.4" spread="26.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score</title>
        <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L system and EQ-VAS. EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, and Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health), a lower score indicates worse health. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Sum score ranges from 0-100. Higher score indicates a more severe problem. Negative change in score indicates improvement.</description>
        <time_frame>Baseline, Days 2, 11 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score</title>
          <description>EQ-5D-5L measures health outcome. It consists of EQ-5D-5L system and EQ-VAS. EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, and Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health &quot;today&quot;. Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health), a lower score indicates worse health. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Sum score ranges from 0-100. Higher score indicates a more severe problem. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase, have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="111"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.1" spread="12.28"/>
                    <measurement group_id="O2" value="-11.2" spread="14.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.3" spread="16.23"/>
                    <measurement group_id="O2" value="-15.2" spread="15.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13.4" spread="18.05"/>
                    <measurement group_id="O2" value="-16.8" spread="16.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase</title>
        <description>The QLDS is a disease specific patient-reported outcome designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of &quot;at the moment&quot;, contains 34-items with &quot;true&quot;/&quot;not true&quot; response options and takes approximately 5-10 minutes to complete. The total score range is from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.</description>
        <time_frame>Baseline and Days 2, 11 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase</title>
          <description>The QLDS is a disease specific patient-reported outcome designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of &quot;at the moment&quot;, contains 34-items with &quot;true&quot;/&quot;not true&quot; response options and takes approximately 5-10 minutes to complete. The total score range is from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="4.55"/>
                    <measurement group_id="O2" value="-3.1" spread="5.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.4" spread="5.93"/>
                    <measurement group_id="O2" value="-5.6" spread="5.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.6" spread="5.99"/>
                    <measurement group_id="O2" value="-6.8" spread="5.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase</title>
        <description>The TSQM-9 is a 9-item generic patient-reported outcome instrument to assess participants' satisfaction with medication. It covers domains of effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores were calculated as recommended by the instrument authors. (i) Effectiveness = [(item 1 + item 2 + item 3) - 3]/18*100, (ii) Convenience = [(item 4 + item 5 + item 6) - 3]/18*100 and (iii) Global satisfaction = [(item 7 + item 8 + item 9) - 3]/14*100. Each domain score can be calculated only if all the three items considered in the calculation of that score are not missing. The TSQM-9 domain score ranges from 0 to 100, with higher scores representing higher satisfaction.</description>
        <time_frame>Days 15 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase</title>
          <description>The TSQM-9 is a 9-item generic patient-reported outcome instrument to assess participants' satisfaction with medication. It covers domains of effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores were calculated as recommended by the instrument authors. (i) Effectiveness = [(item 1 + item 2 + item 3) - 3]/18*100, (ii) Convenience = [(item 4 + item 5 + item 6) - 3]/18*100 and (iii) Global satisfaction = [(item 7 + item 8 + item 9) - 3]/14*100. Each domain score can be calculated only if all the three items considered in the calculation of that score are not missing. The TSQM-9 domain score ranges from 0 to 100, with higher scores representing higher satisfaction.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Effectiveness: Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.7" spread="25.74"/>
                    <measurement group_id="O2" value="63.5" spread="23.72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Effectiveness: Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="57.6" spread="24.66"/>
                    <measurement group_id="O2" value="65.8" spread="25.23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Convenience: Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.9" spread="19.57"/>
                    <measurement group_id="O2" value="70.5" spread="20.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Convenience: Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.0" spread="19.38"/>
                    <measurement group_id="O2" value="71.3" spread="19.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global Satisfaction: Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="105"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="52.2" spread="28.57"/>
                    <measurement group_id="O2" value="64.5" spread="24.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Global Satisfaction: Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.7" spread="27.44"/>
                    <measurement group_id="O2" value="68.5" spread="25.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
        <description>SIBAT is an assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT is organized into 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Patient-reported section has modules of demographics and suicide history, risk/protective factors, suicidal thinking, suicide behavior, and suicide risk. Question 3 from Module 5 asks participants to describe their thinking about suicide right now from 5 response options ranging from 0 (I have no suicidal thoughts) to 4 (I have suicidal thoughts all of time). SIBAT Module 5 (My Risk) Question 3 (Patient-reported FoST) total score ranges from 0 to 4; a higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
        <time_frame>Baseline, Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
          <description>SIBAT is an assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT is organized into 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Patient-reported section has modules of demographics and suicide history, risk/protective factors, suicidal thinking, suicide behavior, and suicide risk. Question 3 from Module 5 asks participants to describe their thinking about suicide right now from 5 response options ranging from 0 (I have no suicidal thoughts) to 4 (I have suicidal thoughts all of time). SIBAT Module 5 (My Risk) Question 3 (Patient-reported FoST) total score ranges from 0 to 4; a higher score indicates a more severe condition. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0" lower_limit="-4" upper_limit="2"/>
                    <measurement group_id="O2" value="0.0" lower_limit="-3" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-4" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4" upper_limit="2"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="103"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.5" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-4" upper_limit="2"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-4" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-4" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 - Clinician-rated FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
        <description>SIBAT is assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT has 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Clinician-rated section has modules for semi-structured interview, clinical global impressions of current severity of suicidality and imminent suicide risk, clinical global impression of long-term suicide risk, and clinical judgment of optimal suicide management. The score anchor point as in participant report frequency of suicidal thinking (FoST) that is, response options from never to all the time. Module 7-FoST score ranges from 0-5; higher score indicates more severe condition. Negative change in score indicates improvement.</description>
        <time_frame>Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 - Clinician-rated FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase</title>
          <description>SIBAT is assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT has 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Clinician-rated section has modules for semi-structured interview, clinical global impressions of current severity of suicidality and imminent suicide risk, clinical global impression of long-term suicide risk, and clinical judgment of optimal suicide management. The score anchor point as in participant report frequency of suicidal thinking (FoST) that is, response options from never to all the time. Module 7-FoST score ranges from 0-5; higher score indicates more severe condition. Negative change in score indicates improvement.</description>
          <population>Full efficacy analysis set included all randomized participants who received at least 1 dose of intranasal study agent during double-blind phase and have had both a baseline and a post-baseline evaluation for MADRS total score or CGI-SS-R. Here, 'n' (number analyzed) signifies number of participants who were analyzed at specified time points.</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="112"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="112"/>
                    <count group_id="O2" value="112"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-1.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="110"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="2"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="0"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-2.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.0" lower_limit="-5" upper_limit="1"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-5" upper_limit="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to study agent.</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to study agent.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83"/>
                    <measurement group_id="O2" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase</title>
        <description>Low/high abnormal values are: Alanine aminotransferase (ALT)-high=200 Units per liter(U/L); ALP-high=250U/L; aspartate aminotransferase(AST)-high=250U/L; gamma glutamyl transferase(GGT)=300U/L; Albumin(low=24g/L,high=60 g/L); Bicarbonate(low=15.1, high=34.9mmol/L); Bilirubin(high=51.3micromol/L); calcium(low=1.5,high=3mmol/L);Chloride(low=94,high=112mmol/L); CK(High=990U/L); Creatinine(High=265.2micromol/L); Eosinophils(High=10%); Erythrocytes(low=3.0*1012/L,high=6.4*1012/L); Glucose(low=2.2,high=16.7mmol/L); Hemoglobin(low=80g/L,high=190g/L);Hematocrit(low=0.28, high=0.55 fraction); LD(high=500U/L); Leukocytes(low=2.5*109/L,high=15.5*109/L); Lymphocytes(low=10%,high=60%); Monocytes(high=20%); Neutrophils(low=30%,high=90%); Phosphate(low=0.7 mmol/L,high=2.6mmol/L); Platelet count(low=100*109/L,high=600*109/L]; Potassium(low=3.0mmol/L,high=5.8 mmol/L]; Protein(low=50 g/L); Sodium(low=125 mmol/L,high=155 mmol/L); Urate(low=89.2 micromol/L,high=594.8micromol/L); Urine(high=8.0 pH).</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here 'n' (number analyzed) signifies number of participants analyzed for each specified category.ULN=upper limit of normal; mmol/L= millimoles per liter; micromol/L=micromole/liter; g/L=gram per liter</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase</title>
          <description>Low/high abnormal values are: Alanine aminotransferase (ALT)-high=200 Units per liter(U/L); ALP-high=250U/L; aspartate aminotransferase(AST)-high=250U/L; gamma glutamyl transferase(GGT)=300U/L; Albumin(low=24g/L,high=60 g/L); Bicarbonate(low=15.1, high=34.9mmol/L); Bilirubin(high=51.3micromol/L); calcium(low=1.5,high=3mmol/L);Chloride(low=94,high=112mmol/L); CK(High=990U/L); Creatinine(High=265.2micromol/L); Eosinophils(High=10%); Erythrocytes(low=3.0*1012/L,high=6.4*1012/L); Glucose(low=2.2,high=16.7mmol/L); Hemoglobin(low=80g/L,high=190g/L);Hematocrit(low=0.28, high=0.55 fraction); LD(high=500U/L); Leukocytes(low=2.5*109/L,high=15.5*109/L); Lymphocytes(low=10%,high=60%); Monocytes(high=20%); Neutrophils(low=30%,high=90%); Phosphate(low=0.7 mmol/L,high=2.6mmol/L); Platelet count(low=100*109/L,high=600*109/L]; Potassium(low=3.0mmol/L,high=5.8 mmol/L]; Protein(low=50 g/L); Sodium(low=125 mmol/L,high=155 mmol/L); Urate(low=89.2 micromol/L,high=594.8micromol/L); Urine(high=8.0 pH).</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here 'n' (number analyzed) signifies number of participants analyzed for each specified category.ULN=upper limit of normal; mmol/L= millimoles per liter; micromol/L=micromole/liter; g/L=gram per liter</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ALT&gt;3*ULN</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Albumin: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Albumin: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alkaline phosphatase (ALP): Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: AST&gt;3*ULN</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AST: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bicarbonate: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bicarbonate: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="99"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Chloride: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatine Kinase (CK): Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Creatinine: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>GGT: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Glucose: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ALT&gt;3*ULN or AST&gt;3*ULN and BILI&gt;2*ULN</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="100"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lactate Dehydrogenase(LD): Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="101"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phosphate: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Phosphate: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Protein: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urate: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urate: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="110"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Basophils: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Eosinophils: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythrocytes: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Erythrocytes: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematocrit: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematocrit: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="96"/>
                    <count group_id="O2" value="103"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin(Hb): Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Leukocytes: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Lymphocytes: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Monocytes: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Platelets: Abnormal Low</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="104"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Urine pH: Abnormal High</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="102"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase</title>
        <description>Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.</description>
        <time_frame>At Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here, 'n' (number analyzed) signifies number of participants analyzed for each specified category.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase</title>
          <description>Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here, 'n' (number analyzed) signifies number of participants analyzed for each specified category.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Epistaxis: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epistaxis: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Epistaxis: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Crusts: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Crusts: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Crusts: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Discharge: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Discharge: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Discharge: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Erythema: Mild</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Erythema: Moderate</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Nasal Erythema: Severe</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="104"/>
                    <count group_id="O2" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase</title>
        <description>Number of participants with treatment emergent abnormal ECG values for variables including heart rate (abnormally low refers to less than or equal to [&lt;=] 50 beats per minute [bpm] , abnormally high refers greater than or equal to [&gt;=] 100 bpm), pulse rate (PR) interval (abnormally high refers to &gt;= 210 milliseconds [msec]), QRS interval (abnormally Low refers to &lt;= 50, abnormally high refers to &gt;= 120 msec) and QT interval (abnormally low refers to &lt;= 200, abnormally high &gt;= 500 msec) were reported.</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase</title>
          <description>Number of participants with treatment emergent abnormal ECG values for variables including heart rate (abnormally low refers to less than or equal to [&lt;=] 50 beats per minute [bpm] , abnormally high refers greater than or equal to [&gt;=] 100 bpm), pulse rate (PR) interval (abnormally high refers to &gt;= 210 milliseconds [msec]), QRS interval (abnormally Low refers to &lt;= 50, abnormally high refers to &gt;= 120 msec) and QT interval (abnormally low refers to &lt;= 200, abnormally high &gt;= 500 msec) were reported.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Heart Rate &lt;= 50 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Heart Rate &gt;= 100 bpm</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PR Duration &gt;= 210 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS Duration &lt;= 50 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QRS Duration &gt;= 120 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT Duration &lt;= 200 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>QT Duration &gt;= 500 msec</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [&lt;] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase</title>
        <description>Pulse oximetry was used to measure arterial SpO2 levels. On each dosing day, the device was attached to the finger, toe, or ear, and SpO2 was monitored and documented. If oxygen saturation levels were less than (&lt;) 93% at any time during the 1.5 hours postdose interval, pulse oximetry was recorded every 5 minutes until levels return to &gt;= 93% or until the participant is referred for appropriate medical care, if clinically indicated. Participants with at least 2 consecutive postdose oxygen saturation below 93% during the DB treatment phase were reported.</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [&lt;] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase</title>
          <description>Pulse oximetry was used to measure arterial SpO2 levels. On each dosing day, the device was attached to the finger, toe, or ear, and SpO2 was monitored and documented. If oxygen saturation levels were less than (&lt;) 93% at any time during the 1.5 hours postdose interval, pulse oximetry was recorded every 5 minutes until levels return to &gt;= 93% or until the participant is referred for appropriate medical care, if clinically indicated. Participants with at least 2 consecutive postdose oxygen saturation below 93% during the DB treatment phase were reported.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase</title>
        <description>Number of participants with treatment emergent vital signs abnormalities (pulse rate in bpm [abnormally low = a decrease from baseline of &gt;= 15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;=15 to a value &gt;=100] , systolic blood pressure [SBP] in mmHg [abnormally low = a decrease from baseline of &gt;= 20 to a value &lt;= 90; abnormally high = an increase from baseline of &gt;= 20 to a value &gt;= 180], and diastolic blood pressure [DBP] in mmHg [abnormally low= a decrease from baseline of &gt;=15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;= 15 to a value &gt;= 105) were reported.</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase</title>
          <description>Number of participants with treatment emergent vital signs abnormalities (pulse rate in bpm [abnormally low = a decrease from baseline of &gt;= 15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;=15 to a value &gt;=100] , systolic blood pressure [SBP] in mmHg [abnormally low = a decrease from baseline of &gt;= 20 to a value &lt;= 90; abnormally high = an increase from baseline of &gt;= 20 to a value &gt;= 180], and diastolic blood pressure [DBP] in mmHg [abnormally low= a decrease from baseline of &gt;=15 to a value &lt;= 50; abnormally high = an increase from baseline of &gt;= 15 to a value &gt;= 105) were reported.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Pulse rate (bpm): Decrease of &gt;=15 to &lt;=50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Pulse rate (bpm): Increase of &gt;=15 to &gt;=100</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP (mmHg): Decrease of &gt;=20 to &lt;=90</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SBP (mmHg): Increase of &gt;=20 to &gt;=180</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP (mmHg): Decrease of &gt;=15 to &lt;=50</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DBP (mmHg): Increase of &gt;=15 to &gt;=105</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase</title>
        <description>MOAA/S was used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American society of anesthesiologists (ASA) continuum. The MOAA/S scores range from 0 to 5 where,0 = no response to painful stimulus; ASA continuum = general anesthesia, 1 = responds to trapezius squeeze; ASA continuum = deep sedation, 2 = purposeful response to mild prodding or mild shaking; ASA continuum = moderate sedation, 3 = responds after name called loudly or repeatedly; ASA continuum = moderate sedation, 4 = lethargic response to name spoken in normal tone; ASA continuum = moderate sedation and 5 = readily responds to name spoken in normal tone (awake); ASA continuum = minimal sedation.</description>
        <time_frame>Up to Day 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase</title>
          <description>MOAA/S was used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American society of anesthesiologists (ASA) continuum. The MOAA/S scores range from 0 to 5 where,0 = no response to painful stimulus; ASA continuum = general anesthesia, 1 = responds to trapezius squeeze; ASA continuum = deep sedation, 2 = purposeful response to mild prodding or mild shaking; ASA continuum = moderate sedation, 3 = responds after name called loudly or repeatedly; ASA continuum = moderate sedation, 4 = lethargic response to name spoken in normal tone; ASA continuum = moderate sedation and 5 = readily responds to name spoken in normal tone (awake); ASA continuum = minimal sedation.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Score &lt;=2: Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Score &lt;=3: Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Score &lt;=4: Yes</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase</title>
        <description>The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = &quot;Not at all&quot;, 1 = &quot;Mild&quot;, 2 = &quot;Moderate&quot;, 3 = 'Severe&quot; and 4 = &quot;Extreme&quot;). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition. Number of participants with an increase in CADSS total score (increase based on maximum CADSS total score change from predose of &gt; 0) was reported.</description>
        <time_frame>Days 1, 4, 8, 11, 15, 18, 22 and 25</time_frame>
        <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here, 'n' (number analyzed) signifies the number of participants analyzed for each specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
          <group group_id="O2">
            <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
            <description>Participants self-administered esketamine 84 milligrams (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) and received SOC antidepressant treatment which was initiated or optimized on Day 1.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase</title>
          <description>The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = &quot;Not at all&quot;, 1 = &quot;Mild&quot;, 2 = &quot;Moderate&quot;, 3 = 'Severe&quot; and 4 = &quot;Extreme&quot;). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition. Number of participants with an increase in CADSS total score (increase based on maximum CADSS total score change from predose of &gt; 0) was reported.</description>
          <population>Safety analysis set included all randomized participants who received at least 1 dose of study drug in the DB treatment phase. Here, 'n' (number analyzed) signifies the number of participants analyzed for each specified time point.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="112"/>
                <count group_id="O2" value="113"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="111"/>
                    <count group_id="O2" value="113"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="34"/>
                    <measurement group_id="O2" value="95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="107"/>
                    <count group_id="O2" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23"/>
                    <measurement group_id="O2" value="84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="108"/>
                    <count group_id="O2" value="108"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29"/>
                    <measurement group_id="O2" value="81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="101"/>
                    <count group_id="O2" value="100"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 15</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="97"/>
                    <count group_id="O2" value="105"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="17"/>
                    <measurement group_id="O2" value="69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="92"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="93"/>
                    <count group_id="O2" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="70"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Day 25</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="91"/>
                    <count group_id="O2" value="98"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to Day 25</time_frame>
      <desc>Safety analysis set included all randomized participants who received at least 1 dose of study agent in the double-blind treatment phase.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo Plus SOC Antidepressant Treatment</title>
          <description>Subjects self-administered placebo matched to esketamine intranasally (1 spray of placebo to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received standard of care (SOC) antidepressant treatment which was initiated or optimized on Day 1 during double blind phase (DB).</description>
        </group>
        <group group_id="E2">
          <title>Esketamine 84 mg Plus SOC Antidepressant Treatment</title>
          <description>Subjects self-administered esketamine 84 milligram (mg) intranasally (1 spray of esketamine 14 mg to each nostril at 0, 5 and 10 minutes) twice per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) plus received SOC antidepressant treatment which was initiated or optimized on Day 1 during double blind phase.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA Version 21.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertransaminasaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic Ketoacidosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Aggression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Depression Suicidal</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Suicidal Ideation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Suicide Attempt</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA Version 21.1</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="91" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Vision Blurred</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood Pressure Increased</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Dizziness Postural</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="16" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="20" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Sedation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Dissociation</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="33" subjects_at_risk="113"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="112"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="113"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>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.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Esketamine's known characteristic effects such as dissociative symptoms, sedation, and elevation of blood pressure may have impact on blinding, to minimize this bias, protocol specified that different raters perform efficacy and safety assessments.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Senior Director</name_or_title>
      <organization>Janssen Research &amp; Development, LLC</organization>
      <phone>844-434-4210</phone>
      <email>ClinicalTrialDisclosure@its.jnj.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03039192
org study id: CR108284
secondary id: 2016-003990-17
secondary id: 54135419SUI3001
nct id: NCT03039192
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of the 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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in Montgomery Asberg Depression Rating Scale (MADRS) Total Score at 24 Hours After the First Dose (Day 2) (Last Observation Carried Forward [LOCF] Data) During Double-blind Phase
time frame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
description: MADRS is clinician-rated scale designed to be used in participants with Major Depressive Disorder (MDD) to measure depression severity and detect changes due to antidepressant treatment. It evaluates apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic and suicidal thoughts. Scale consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of symptoms), summed for total possible score of 0 to 60. Higher scores represent more severe condition. Negative change in score indicates improvement.
measure: Change From Baseline in Clinical Global Impression of Severity of Suicidality- Revised (CGI-SS-R) Score at 24 Hours After the First Dose (Day 2) (LOCF Data) During Double-blind Phase
time frame: Baseline (Day 1, predose) and 24 hours first post dose (Day 2)
description: CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition and a reduction in score indicates improvement (that is, lower severity of suicidality).
measure: Number of Participants Who Achieved Remission (MADRS Total Score Less Than or Equal to [<=] 12) Through the Double-blind Phase
time frame: Days 1 (4 hours postdose), 2, 4, 8, 11, 15, 18, 22 and Day 25 (predose and 4 hours postdose)
description: Participants who had a MADRS total score of <=12 were considered remitters. MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.
measure: Change From Baseline in Montgomery Asberg Depression Rating Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
time frame: Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 (predose and 4 hours postdose)
description: MADRS is clinician-rated scale designed to measure depression severity, and to detect changes due to antidepressant treatment. Scale consists of 10 items (apparent sadness, reported sadness, inner tension, sleep, appetite, concentration, lassitude, interest level, pessimistic thoughts, and suicidal thoughts), each of which is scored from 0 (item is not present or is normal) to 6 (severe or continuous presence of symptoms), summed for a total possible score of 0 to 60. Higher scores represent more severe condition and a negative change in score indicates improvement.
measure: Change From Baseline in Clinical Global Impression- Severity of Suicidality-Revised (CGI-SS-R) at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
time frame: Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
description: CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement.
measure: Number of Participants Who Achieved Resolution of Suicidality (CGI-SS-R Score of 0 or 1) Through Double-blind Phase
time frame: Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
description: CGI-SS-R was derived from the Clinical Global Impression Severity Scale (CGI-S), a global rating scale that gives an overall measure of the severity of a participants illness. The CGI-SS-R rating is scored on a 7-point scale from 0 (normal, not at all suicidal) to 6 (among the most extremely suicidal participants). A higher score indicates a more severe condition. Negative change in score indicates improvement. A participant was considered to achieve resolution of suicidality at a given time point if the CGI-SS-R score was 0 (normal, not at all suicidal) or 1 (questionably suicidal).
measure: Change From Baseline in Clinical Global Impression of Imminent Suicide Risk (CGI-SR-I) Scale Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
time frame: Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
description: The CGI-SR-I is a scale summarizing the clinician's best assessment of the likelihood that the participant will attempt suicide in the next 7 days. The CGI-SR-I rating is scored on a 7-point scale: where' 0 (no imminent suicide risk); 1 (minimal imminent suicide risk), 2 (mild imminent suicide risk), 3 (moderate imminent suicide risk), 4 (marked imminent suicide risk), 5 (severely imminent suicide risk), 6 (extreme imminent suicide risk). Higher score indicates a more severe condition. Negative change in score indicates improvement.
measure: Change From Baseline in Beck Hopelessness Scale (BHS) Total Score at Days 8 and 25 During Double-blind Phase
time frame: Baseline, Days 8 and 25
description: BHS is a self-reported measure to assess one's level of negative expectations or pessimism regarding future. It consists of 20 true-false items that examine respondent's attitude over past week by either endorsing a pessimistic statement or denying an optimistic statement; 9 are keyed false and 11 are keyed true. For every statement, each response was assigned score of 0 or 1. Total BHS score is sum of item responses, ranged from 0-20, where higher score represented higher level of hopelessness.
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Health Status Index
time frame: Baseline and Days 2, 11 and 25
description: EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and EQ visual analogue scale (EQ-VAS). EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health). Positive change in score indicates improvement.
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: EQ-Visual Analogue Scale (EQ-VAS)
time frame: Baseline, Days 2, 11 and 25
description: EQ-5D-5L measures health outcome. It consists of EQ-5D-5L descriptive system and the EQ visual analogue scale (EQ-VAS). EQ-VAS score from 0 (worst health) to 100 (best health), positive change in score indicates improvement.
measure: Change From Baseline in EuroQol-5 Dimension-5 Level (EQ-5D-5L) at Days 2, 11 and 25 During Double-blind Phase: Sum Score
time frame: Baseline, Days 2, 11 and 25
description: EQ-5D-5L measures health outcome. It consists of EQ-5D-5L system and EQ-VAS. EQ-5D-5L system comprises following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (Level 1-no problem, Level 2-slight problems, Level 3-moderate problems, Level 4-severe problems, and Level 5-extreme problems). Participant selects answer for each of 5 dimensions considering response that best matches his/her health "today". Responses were used to generate a health status index (HSI). Health Status Index ranges from 0.148 - 0.949, anchored at 0 (dead) and 1 (full health), a lower score indicates worse health. Sum score=(sum of the scores from the 5 dimensions minus 5)*5. Sum score ranges from 0-100. Higher score indicates a more severe problem. Negative change in score indicates improvement.
measure: Change From Baseline in Quality of Life in Depression Scale (QLDS) Total Score at Days 2, 11 and 25 During Double-blind Phase
time frame: Baseline and Days 2, 11 and 25
description: The QLDS is a disease specific patient-reported outcome designed to assess health related quality of life in participants with major depressive disorder (MDD). The instrument has a recall period of "at the moment", contains 34-items with "true"/"not true" response options and takes approximately 5-10 minutes to complete. The total score range is from 0 (good quality of life) to 34 (very poor quality of life). A higher score indicates a more severe condition. Negative change indicates improvement.
measure: Treatment Satisfaction Questionnaire for Medication (TSQM-9) Total Score at Days 15 and 25 During Double-blind Phase
time frame: Days 15 and 25
description: The TSQM-9 is a 9-item generic patient-reported outcome instrument to assess participants' satisfaction with medication. It covers domains of effectiveness, convenience, and global satisfaction. The TSQM-9 domain scores were calculated as recommended by the instrument authors. (i) Effectiveness = [(item 1 + item 2 + item 3) - 3]/18*100, (ii) Convenience = [(item 4 + item 5 + item 6) - 3]/18*100 and (iii) Global satisfaction = [(item 7 + item 8 + item 9) - 3]/14*100. Each domain score can be calculated only if all the three items considered in the calculation of that score are not missing. The TSQM-9 domain score ranges from 0 to 100, with higher scores representing higher satisfaction.
measure: Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 5 (My Risk) Question 3 (Patient-reported FoST) Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
time frame: Baseline, Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
description: SIBAT is an assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT is organized into 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Patient-reported section has modules of demographics and suicide history, risk/protective factors, suicidal thinking, suicide behavior, and suicide risk. Question 3 from Module 5 asks participants to describe their thinking about suicide right now from 5 response options ranging from 0 (I have no suicidal thoughts) to 4 (I have suicidal thoughts all of time). SIBAT Module 5 (My Risk) Question 3 (Patient-reported FoST) total score ranges from 0 to 4; a higher score indicates a more severe condition. Negative change in score indicates improvement.
measure: Change From Baseline in Suicide Ideation and Behavior Assessment Tool (SIBAT) Module 7 - Clinician-rated FoST Total Score at Days 1, 2, 4, 8, 11, 15, 18, 22 and 25 During Double-blind Phase
time frame: Baseline and Days 1, 2, 4, 8, 11, 15, 18, 22 and 25
description: SIBAT is assessment tool that captures suicidal ideation, behavior, and risk. It permits assessment of change in suicidal ideation and behavior and documents clinician assessment of severity of suicidality and suicide risk. SIBAT has 8 modules divided into 2 major divisions: patient-reported section (Modules 1-5) and clinician-rated section (Modules 6-8). Clinician-rated section has modules for semi-structured interview, clinical global impressions of current severity of suicidality and imminent suicide risk, clinical global impression of long-term suicide risk, and clinical judgment of optimal suicide management. The score anchor point as in participant report frequency of suicidal thinking (FoST) that is, response options from never to all the time. Module 7-FoST score ranges from 0-5; higher score indicates more severe condition. Negative change in score indicates improvement.
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs): DB Treatment Phase
time frame: Up to Day 25
description: An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal (investigational or non investigational) product, whether or not related to that medicinal (investigational or non-investigational) product. A TEAE is categorized as related if assessed by the investigator as possibly, probably, or very likely related to study agent.
measure: Number of Participants With Treatment Emergent Abnormal Laboratory Values: DB Treatment Phase
time frame: Up to Day 25
description: Low/high abnormal values are: Alanine aminotransferase (ALT)-high=200 Units per liter(U/L); ALP-high=250U/L; aspartate aminotransferase(AST)-high=250U/L; gamma glutamyl transferase(GGT)=300U/L; Albumin(low=24g/L,high=60 g/L); Bicarbonate(low=15.1, high=34.9mmol/L); Bilirubin(high=51.3micromol/L); calcium(low=1.5,high=3mmol/L);Chloride(low=94,high=112mmol/L); CK(High=990U/L); Creatinine(High=265.2micromol/L); Eosinophils(High=10%); Erythrocytes(low=3.0*1012/L,high=6.4*1012/L); Glucose(low=2.2,high=16.7mmol/L); Hemoglobin(low=80g/L,high=190g/L);Hematocrit(low=0.28, high=0.55 fraction); LD(high=500U/L); Leukocytes(low=2.5*109/L,high=15.5*109/L); Lymphocytes(low=10%,high=60%); Monocytes(high=20%); Neutrophils(low=30%,high=90%); Phosphate(low=0.7 mmol/L,high=2.6mmol/L); Platelet count(low=100*109/L,high=600*109/L]; Potassium(low=3.0mmol/L,high=5.8 mmol/L]; Protein(low=50 g/L); Sodium(low=125 mmol/L,high=155 mmol/L); Urate(low=89.2 micromol/L,high=594.8micromol/L); Urine(high=8.0 pH).
measure: Number of Participants With Abnormal Nasal Examinations at Day 25: DB Treatment Phase
time frame: At Day 25
description: Number of participants with abnormal nasal examination were reported. Nasal examination of visual inspection of the epistaxis, nasal crusts, nasal discharge, and nasal erythema was performed.
measure: Number of Participants With Treatment Emergent Abnormal Electrocardiogram (ECG) Values at Any Time: DB Treatment Phase
time frame: Up to Day 25
description: Number of participants with treatment emergent abnormal ECG values for variables including heart rate (abnormally low refers to less than or equal to [<=] 50 beats per minute [bpm] , abnormally high refers greater than or equal to [>=] 100 bpm), pulse rate (PR) interval (abnormally high refers to >= 210 milliseconds [msec]), QRS interval (abnormally Low refers to <= 50, abnormally high refers to >= 120 msec) and QT interval (abnormally low refers to <= 200, abnormally high >= 500 msec) were reported.
measure: Number of Participants With Abnormal Arterial Oxygen Saturation (SpO2) Levels (Less Than [<] 93%) as Assessed by Pulse Oximetry at Any Time: DB Treatment Phase
time frame: Up to Day 25
description: Pulse oximetry was used to measure arterial SpO2 levels. On each dosing day, the device was attached to the finger, toe, or ear, and SpO2 was monitored and documented. If oxygen saturation levels were less than (<) 93% at any time during the 1.5 hours postdose interval, pulse oximetry was recorded every 5 minutes until levels return to >= 93% or until the participant is referred for appropriate medical care, if clinically indicated. Participants with at least 2 consecutive postdose oxygen saturation below 93% during the DB treatment phase were reported.
measure: Number of Participants With Treatment Emergent Vital Signs Abnormalities: DB Treatment Phase
time frame: Up to Day 25
description: Number of participants with treatment emergent vital signs abnormalities (pulse rate in bpm [abnormally low = a decrease from baseline of >= 15 to a value <= 50; abnormally high = an increase from baseline of >=15 to a value >=100] , systolic blood pressure [SBP] in mmHg [abnormally low = a decrease from baseline of >= 20 to a value <= 90; abnormally high = an increase from baseline of >= 20 to a value >= 180], and diastolic blood pressure [DBP] in mmHg [abnormally low= a decrease from baseline of >=15 to a value <= 50; abnormally high = an increase from baseline of >= 15 to a value >= 105) were reported.
measure: Number of Sedated Participants as Assessed by Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Score at Any Time: DB Treatment Phase
time frame: Up to Day 25
description: MOAA/S was used to measure treatment-emergent sedation with correlation to levels of sedation defined by the American society of anesthesiologists (ASA) continuum. The MOAA/S scores range from 0 to 5 where,0 = no response to painful stimulus; ASA continuum = general anesthesia, 1 = responds to trapezius squeeze; ASA continuum = deep sedation, 2 = purposeful response to mild prodding or mild shaking; ASA continuum = moderate sedation, 3 = responds after name called loudly or repeatedly; ASA continuum = moderate sedation, 4 = lethargic response to name spoken in normal tone; ASA continuum = moderate sedation and 5 = readily responds to name spoken in normal tone (awake); ASA continuum = minimal sedation.
measure: Number of Participants With an Increase in Clinician-administered Dissociative States Scale (CADSS) Total Score Over Time: DB Treatment Phase
time frame: Days 1, 4, 8, 11, 15, 18, 22 and 25
description: The CADSS used to measure present-state dissociative symptoms, and to assess treatment-emergent dissociative symptoms. It comprises 23 subjective items divided into 3 components: depersonalization (with score range from 0 to 28), derealization (with score range from 0 to 52), and amnesia (with score range from 0 to 8). Participants responses are coded on a 5-point scale (0 = "Not at all", 1 = "Mild", 2 = "Moderate", 3 = 'Severe" and 4 = "Extreme"). The total score is sum of the 23 items and range from 0 to 92, where 0 (best) and 92 (worst). A higher score indicates a more severe condition. Number of participants with an increase in CADSS total score (increase based on maximum CADSS total score change from predose of > 0) was reported.
arm group label: Esketamine + Standard of care
arm group type: Experimental
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) along with standard of care (SOC) antidepressant treatment.
arm group label: Placebo + Standard of care
arm group type: Placebo Comparator
description: Participants will receive intranasal placebo two times per week for 4 weeks (Days 1, 4, 8, 11, 15, 18, 22, and 25) along with standard of care antidepressant treatment.
intervention type: Drug
intervention name: Esketamine
description: Intranasal esketamine solution 84 milligram (mg)
arm group label: Esketamine + Standard of care
intervention type: Other
intervention name: Placebo
description: Intranasal Placebo solution
arm group label: Placebo + Standard of care
intervention type: Other
intervention name: Standard of Care
description: 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.
arm group label: Esketamine + Standard of care
arm group label: Placebo + Standard of care
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
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country: Bulgaria
country: Estonia
country: Germany
country: Hungary
country: Korea, Republic of
country: Malaysia
country: Slovakia
country: South Africa
country: Spain
country: Taiwan
country: United States
url: https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=CR108284&attachmentIdentifier=0b008702-9e7b-4d11-b853-d3aba96bb3a1&fileName=54135419SUI3001_(CR108284)_Additional_Results_Data_CH.pdf&versionIdentifier=
description: 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 (Aspire I)
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Suicide
mesh term: Suicidal Ideation
mesh term: Esketamine
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Esketamine's known characteristic effects such as dissociative symptoms, sedation, and elevation of blood pressure may have impact on blinding, to minimize this bias, protocol specified that different raters perform efficacy and safety assessments.
point of contact: 