<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/NCT03756129</url>
  </required_header>
  <id_info>
    <org_study_id>CMIJ821X2201</org_study_id>
    <nct_id>NCT03756129</nct_id>
  </id_info>
  <brief_title>Proof of Concept Study Evaluating the Efficacy and Safety of MIJ821 in Patients With Treatment-resistant Depression</brief_title>
  <official_title>A Multi-center, Randomized, subject-and Investigator Blinded, Placebo-controlled, Active Comparator, Parallel-group Proof of Concept Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of MIJ821 in Patients With Treatment-resistant Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</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>
      This study evaluated the efficacy and safety of the compound MIJ821 compared to placebo in&#xD;
      patients aged from 18 to 65 years diagnosed with treatment-resistant depression. The study&#xD;
      was conducted in the US and in Europe (Spain). The MIJ821 was administered via infusion on a&#xD;
      weekly or bi-weekly basis. The efficacy was measured after 24 hours using a specific golden&#xD;
      standard scale, the Montgomery-Asberg Depression Rating Scale. The study duration was 6 weeks&#xD;
      of treatment plus 1 month of follow up period.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This was a non-confirmatory, multi-center, 6-treatment arm in European (Spain) and&#xD;
      5-treatment arm in the US (no ketamine arm), randomized, subject and investigator blinded,&#xD;
      parallel-group, placebo-controlled study in patients with treatment-resistant depression. The&#xD;
      total duration for each subject in the study was maximum 14 weeks: a screening period of&#xD;
      maximum 4 weeks, a 36-day treatment period and a 5-week follow-up period.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 8, 2019</start_date>
  <completion_date type="Actual">March 23, 2020</completion_date>
  <primary_completion_date type="Actual">March 23, 2020</primary_completion_date>
  <phase>Phase 2</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>
    <intervention_model_description>This is a non-confirmatory, multi-center, 6-treatment arm in the EU countries and 5-treatment arm in the USA (no ketamine arm), randomized, subject and investigator blinded, parallel group, placebo controlled study in treatment-resistant depression patients. The study allows for the inclusion of subjects seeking treatment for their disease from both an 'inpatient' or 'outpatient' clinic setting.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs</measure>
    <time_frame>Baseline, and at 24 hours</time_frame>
    <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs</measure>
    <time_frame>Baseline, and at 48 hours</time_frame>
    <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6</measure>
    <time_frame>Baseline, and at Week 6</time_frame>
    <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Young Mania Rating Scale</measure>
    <time_frame>Baseline, 24 hours, and 6 weeks (day 43)</time_frame>
    <description>To assess risk of mania induction. The Young Mania Rating Scale has 11 items and is based on the patient's subjective report of his/her clinical condition over the previous 48 hours. There are 4 items that are scored from 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior) and the remaining items are scored from 0 to 4. Higher scores indicate more severe mania.&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total YMRS score is 60. The range is 0 to 60 with the higher score indicating more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bech-Rafaelsen Melancholia Scale</measure>
    <time_frame>Baseline, 24 hours, 48 hours and 6 weeks (Day 43)</time_frame>
    <description>To assess efficacy in the melancholic subtype of depression. Depression scales are used primarily to measure changes, for example, to evaluate the efficacy of treatment with antidepressants. The Bech-Rafaelsen Melancholia Scale (BRMS) is a frequently used clinician rating scale to assess the severity of depression over the past 3 days. Each of the 11 BRMS items is operationally defined on a five-point scale (0-4); hence, the total score ranges from 0 to 44, higher scores indicating greater severity of depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Properties of MIJ821 in Plasma - Cmax (ng/mL)</measure>
    <time_frame>Day 1</time_frame>
    <description>To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Properties of MIJ821 in Plasma - Tmax (ng/mL)</measure>
    <time_frame>Day 1</time_frame>
    <description>To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)</measure>
    <time_frame>Day 1</time_frame>
    <description>To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)</measure>
    <time_frame>Day 1</time_frame>
    <description>To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the CORE Melancholia Total Scale</measure>
    <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
    <description>To assess efficacy in melancholic subtype of depression. This scale is an 18 item scale, with a 6 item component capturing cognitive impairment and two motoric scales capturing psychomotor retardation (7 items) and psychomotor agitation (5 items). A cut-off score of 8 or more has been shown to ifferentiate melancholic from non-melancholic depression, with higher scores representing a greater probability of melancholic depression. (Parker and McCraw 2017).&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total CORE Melancholia score is 54. The range is 0 to 54 with the higher score indicating more severe symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary of Adverse Events</measure>
    <time_frame>Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.</time_frame>
    <description>Summary of Adverse Events</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinician-Administered Dissociative States Scale</measure>
    <time_frame>Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
    <description>To assess safety and tolerability, especially dissociative side effects. The Clinical-Administered Dissociative States Scale (CADSS) is a questionnaire that assesses dissociative effects. Each item is scored from 0 to 4 and individual scores are to be summed to obtain a total score ranging from a minimum of 0 to a maximum of 80. Higher scores represent a more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Dissociative Experiences Total Score</measure>
    <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
    <description>The Dissociative Experiences Scale (DES) consists of twenty-eight questions about experiences the subject has experienced in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sheehan Suicidality Tracking Scale - (SSTS)</measure>
    <time_frame>Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
    <description>Sheehan suicidality tracking scale(S-STS) is a fourteen-item (up to 22) scale. Each item in the S-STS is scored on a 5-point Likert scale (0=not at all, 1= a little, 2=moderately, 3=very, and 4=extremely). Data from the S-STS will be analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3 and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a and 8, plus score from item 5 if &gt;1). Higher scores represent a more severe condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Treatment Remissions (MADRS&lt;7)</measure>
    <time_frame>24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
    <description>Percentage of Participants with treatment remissions as assessed via (MADRS&lt;7)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Total Hamilton Anxiety Scale</measure>
    <time_frame>Baseline, and at 6 weeks (day 43)</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline</measure>
    <time_frame>Change from baseline at week 6 (Day 43)</time_frame>
    <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale</measure>
    <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
    <description>The Koukopoulos Mixed Depression Rating Scale (KMDRS) assesses the excitatory or mixed nature in patients suffering from a Major Depressive Episode (MDE) as defined by DSM-5 criteria. This scale is meant to be used in conjunction with another scale that assess typical depression and anxiety symptoms. The scale contains 14 items to be evaluated by clinical assessment and patient interview on symptoms potentially experienced over the past week. Overall score increases with severity of symptoms and has a maximum score of 51. (Sani et al 2018).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Responders (&gt;50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.</measure>
    <time_frame>24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
    <description>Percentage of Participants who responded. The first mixed depression checklist, created by Koukopoulos, has 8 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then mixed depression would be diagnosed. The second mixed depression checklist, created by Angst, lists the 7 criteria for mania from DSM-5, which are marked as present or absent. If 3 or more criteria are marked present, excluding any duration criterion, then mixed depression would be diagnosed. The melancholia checklist, created by Ghaemi for this study, has 4 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then melancholia would be diagnosed.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">70</enrollment>
  <condition>Depressive Disorder, Treatment-Resistant</condition>
  <arm_group>
    <arm_group_label>MIJ821 low dose weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion. MIJ821 low dose weekly - 0.16 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MIJ821 low dose bi-weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion. MIJ821 low dose bi-weekly - 0.16 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MIJ821 high dose weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion. MIJ821 high dose weekly - 0.32 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>MIJ821 high dose bi-weekly</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infusion. MIJ821 high dose bi-weekly - 0.32 mg/kg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo weekly</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Infusion. Placebo weekly</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ketamine 0.5 mg/kg weekly</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Infusion. Ketamine 0.5 mg/kg weekly</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MIJ821</intervention_name>
    <description>Different dosages and different regimen for MIJ821</description>
    <arm_group_label>MIJ821 high dose bi-weekly</arm_group_label>
    <arm_group_label>MIJ821 high dose weekly</arm_group_label>
    <arm_group_label>MIJ821 low dose bi-weekly</arm_group_label>
    <arm_group_label>MIJ821 low dose weekly</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Infusion</description>
    <arm_group_label>Placebo weekly</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Infusion</description>
    <arm_group_label>Ketamine 0.5 mg/kg weekly</arm_group_label>
    <other_name>Ketamine dose to be capped at 40 mg/day for patients over 80 kg</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Signed informed consent.&#xD;
&#xD;
          -  Male and female subjects, 18 to 65 years of age (inclusive) at screening.&#xD;
&#xD;
          -  SCID-based DSM-5 defined major depressive episode at the time of screening&#xD;
&#xD;
          -  Montgomery-Åsberg Depression Rating Scale (MADRS) score ≥ 24 at screening and baseline&#xD;
&#xD;
          -  Failure to respond to two or more antidepressant treatments, where two failed&#xD;
             treatments are of two different antidepressants and at least one of which is in the&#xD;
             current depressive episode, with adequate dose and duration (≥ 8 weeks duration, doses&#xD;
             defined per agent), as identified by the Maudsley Treatment Inventory, and prior&#xD;
             psychiatric history, assessed by the investigator, and further documented by medical&#xD;
             records and/or third party report (family, friends, clinician-treaters) where&#xD;
             available&#xD;
&#xD;
          -  If patients are taking any type of psychotropic drugs, a stable dose of psychotropic&#xD;
             drugs at screening is defined as no changes in dose or type of antidepressants,&#xD;
             antipsychotics, or mood stabilizers for at least 2 weeks prior to screening, if&#xD;
             applicable.&#xD;
&#xD;
          -  No new antidepressant initiated 4 weeks or less before baseline, and 6 weeks or less&#xD;
             before baseline if subject is initiated on fluoxetine&#xD;
&#xD;
          -  At least one prior clinical depressive episode (recurrent major depressive disorder),&#xD;
             as identified by prior psychiatric history assessed by the investigator, and further&#xD;
             documented by medical records and third party report (family, friends,&#xD;
             clinician-treaters) where available.&#xD;
&#xD;
          -  Able to communicate well, and to understand and comply with study requirements&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Any current diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder&#xD;
             at screening.&#xD;
&#xD;
          -  Current alcohol or substance use disorder (including marijuana and prescribed&#xD;
             amphetamine)) meeting DSM-5 criteria, within the past month at baseline. Nicotine and&#xD;
             caffeine use disorders will not be considered as exclusionary.&#xD;
&#xD;
          -  Prior suicidality caused by or associated with ketamine, as identified by prior&#xD;
             psychiatric history assessed by the investigator, and augmented by medical records and&#xD;
             third party report (family, friends, clinician-treaters) where available.&#xD;
&#xD;
          -  Acute serious and/or imminent suicidal ideation and/or intent within the prior 2&#xD;
             weeks, or any suicide attempt within the prior 4 weeks at screening. Mild to moderate&#xD;
             suicidal ideation, using the Sheehan Suicidal Ideation Scale and not meeting the above&#xD;
             definition, is not an exclusion criterion.&#xD;
&#xD;
          -  Use of other investigational drugs within 30 days or 5 half-lives of randomization,&#xD;
             whichever was longer; or longer if required by local regulations at baseline&#xD;
&#xD;
          -  Current pregnancy or lactation.&#xD;
&#xD;
          -  Positive HIV, Hepatitis B or C test.&#xD;
&#xD;
          -  Resting QTcF ≥450 msec (male) or ≥460 msec (female) at pre-treatment baseline&#xD;
&#xD;
          -  History of multiple and recurring allergies or allergy to the investigational&#xD;
             compound/compound class being used in this study.&#xD;
&#xD;
          -  History of malignancy of any organ system (other than localized basal cell carcinoma&#xD;
             of the skin or in-situ cervical cancer), treated or untreated, within the past 3&#xD;
             years, regardless of whether there is evidence of local recurrence or metastases.&#xD;
&#xD;
          -  Women of child-bearing potential, defined as all women physiologically capable of&#xD;
             becoming pregnant, unless they are using highly effective methods of contraception&#xD;
             during dosing and for 1 week after stopping of investigational drug.&#xD;
&#xD;
          -  History of hypersensitivity to any of the study treatments or excipients or to drugs&#xD;
             similar to chemical classes that affect NMDA receptor.&#xD;
&#xD;
          -  Current diagnosis of borderline personality disorder or antisocial personality&#xD;
             disorder, based on DSM-5 criteria.&#xD;
&#xD;
          -  Current acute depressive episode lasting longer than two years continuously, defined&#xD;
             as no two week or longer period where depressive symptoms are subsyndromal in severity&#xD;
             for a full DSM-5 acute major depressive episode.&#xD;
&#xD;
          -  Considered by the investigator, for any other reason, to be an unsuitable candidate&#xD;
             for the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Oakland</city>
        <state>California</state>
        <zip>94607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Bradenton</city>
        <state>Florida</state>
        <zip>34201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Rockville</city>
        <state>Maryland</state>
        <zip>20850</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <state>Catalunya</state>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Palma De Mallorca</city>
        <state>Islas Baleares</state>
        <zip>07120</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Vitoria-Gasteiz</city>
        <state>Pais Vasco</state>
        <zip>01004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Novartis Investigative Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=721</url>
    <description>A Plain Language Trial Summary is available on novartisclinicaltrials.com</description>
  </link>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <results_first_submitted>February 15, 2021</results_first_submitted>
  <results_first_submitted_qc>April 28, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 19, 2021</results_first_posted>
  <last_update_submitted>October 7, 2021</last_update_submitted>
  <last_update_submitted_qc>October 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Refractory Depression</keyword>
  <keyword>Therapy-Resistant Depression</keyword>
  <keyword>Treatment Resistant Depression</keyword>
  <keyword>MDE</keyword>
  <keyword>MDD</keyword>
  <keyword>Major depressive disorder (MDD)</keyword>
  <keyword>clinical depression</keyword>
  <keyword>major depression</keyword>
  <keyword>unipolar depression</keyword>
  <keyword>unipolar mood disorder</keyword>
  <keyword>depression</keyword>
  <keyword>the blues</keyword>
  <keyword>mood disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Treatment-Resistant</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.</ipd_description>
    <ipd_url>https://www.clinicalstudydatarequest.com/</ipd_url>
  </patient_data>
  <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>July 10, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03756129/Prot_001.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>June 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/29/NCT03756129/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>MIJ821 0.16 mg/kg Weekly</title>
          <description>MIJ821 0.16 mg/kg weekly</description>
        </group>
        <group group_id="P2">
          <title>MIJ821 0.16 mg/kg Biweekly</title>
          <description>MIJ821 0.16 mg/kg biweekly</description>
        </group>
        <group group_id="P3">
          <title>MIJ821 0.32 mg/kg Weekly</title>
          <description>MIJ821 0.32 mg/kg weekly</description>
        </group>
        <group group_id="P4">
          <title>MIJ821 0.32 mg/kg Biweekly</title>
          <description>MIJ821 0.32 mg/kg biweekly</description>
        </group>
        <group group_id="P5">
          <title>Ketamine 0.5 mg/kg Weekly</title>
          <description>Ketamine 0.5 mg/kg weekly</description>
        </group>
        <group group_id="P6">
          <title>Placebo Weekly</title>
          <description>Placebo weekly</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="9">1 participant in this group was randomized but not treated, and is not included in this data set.</participants>
                <participants group_id="P5" count="10">1 participant in this group was randomized but not treated, and is not included in this data set.</participants>
                <participants group_id="P6" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="9"/>
                <participants group_id="P6" count="15"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="5"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>MIJ821 0.16 mg/kg Weekly</title>
          <description>MIJ821 0.16 mg/kg weekly</description>
        </group>
        <group group_id="B2">
          <title>MIJ821 0.16 mg/kg Biweekly</title>
          <description>MIJ821 0.16 mg/kg biweekly</description>
        </group>
        <group group_id="B3">
          <title>MIJ821 0.32 mg/kg Weekly</title>
          <description>MIJ821 0.32 mg/kg weekly</description>
        </group>
        <group group_id="B4">
          <title>MIJ821 0.32 mg/kg Biweekly</title>
          <description>MIJ821 0.32 mg/kg biweekly</description>
        </group>
        <group group_id="B5">
          <title>Ketamine 0.5 mg/kg Weekly</title>
          <description>Ketamine 0.5 mg/kg weekly</description>
        </group>
        <group group_id="B6">
          <title>Placebo Weekly</title>
          <description>Placebo weekly</description>
        </group>
        <group group_id="B7">
          <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="11"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="10"/>
            <count group_id="B4" value="9"/>
            <count group_id="B5" value="10"/>
            <count group_id="B6" value="20"/>
            <count group_id="B7" value="70"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="9"/>
                    <measurement group_id="B5" value="10"/>
                    <measurement group_id="B6" value="20"/>
                    <measurement group_id="B7" value="69"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="48.6" spread="11.70"/>
                    <measurement group_id="B2" value="53.7" spread="9.33"/>
                    <measurement group_id="B3" value="42.9" spread="14.47"/>
                    <measurement group_id="B4" value="46.6" spread="11.83"/>
                    <measurement group_id="B5" value="52.3" spread="6.96"/>
                    <measurement group_id="B6" value="44.8" spread="10.69"/>
                    <measurement group_id="B7" value="47.7" spread="11.27"/>
                  </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="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="6"/>
                    <measurement group_id="B5" value="7"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="35"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="3"/>
                    <measurement group_id="B5" value="3"/>
                    <measurement group_id="B6" value="11"/>
                    <measurement group_id="B7" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="1"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="10"/>
                    <measurement group_id="B7" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="9"/>
                    <measurement group_id="B6" value="9"/>
                    <measurement group_id="B7" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                    <measurement group_id="B7" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs</title>
        <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
        <time_frame>Baseline, and at 24 hours</time_frame>
        <population>Intent to Treat analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
          <group group_id="O3">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs</title>
          <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
          <population>Intent to Treat analysis set</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="19"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.51" spread="1.9"/>
                    <measurement group_id="O2" value="-12.98" spread="1.9"/>
                    <measurement group_id="O3" value="-12.94" spread="2.7"/>
                    <measurement group_id="O4" value="-7.27" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;Pooled MIJ821 0.16 mg/kg&quot; minus &quot;placebo&quot;. The MIJ821 treatment arms vs placebo are primary.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0013</p_value>
            <method>ANCOVA</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>-8.25</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.67</ci_lower_limit>
            <ci_upper_limit>-4.83</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;Pooled MIJ821 0.32 mg/kg&quot; minus &quot;placebo&quot;. The MIJ821 treatment arms vs placebo are primary.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0196</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.71</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.22</ci_lower_limit>
            <ci_upper_limit>-2.20</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs</title>
        <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
        <time_frame>Baseline, and at 48 hours</time_frame>
        <population>Intent to Treat analysis set. Please note that some participants missed some visits in the study, and thus data for this outcome measure were not collected for some participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
          <group group_id="O3">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs</title>
          <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
          <population>Intent to Treat analysis set. Please note that some participants missed some visits in the study, and thus data for this outcome measure were not collected for some participants.</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="19"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="4"/>
                <count group_id="O4" value="19"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.94" spread="2.2"/>
                    <measurement group_id="O2" value="-15.25" spread="2.4"/>
                    <measurement group_id="O3" value="-18.89" spread="4.8"/>
                    <measurement group_id="O4" value="-7.88" spread="2.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;Pooled MIJ821 0.16 mg/kg&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0130</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-7.06</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.06</ci_lower_limit>
            <ci_upper_limit>-3.06</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;Pooled MIJ821 0.32 mg/kg&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0133</p_value>
            <method>ANCOVA</method>
            <param_type>Median Difference (Net)</param_type>
            <param_value>-7.37</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.57</ci_lower_limit>
            <ci_upper_limit>-3.18</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6</title>
        <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
        <time_frame>Baseline, and at Week 6</time_frame>
        <population>Intent to Treat analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6</title>
          <description>Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.</description>
          <population>Intent to Treat analysis set</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="9"/>
                <count group_id="O6" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.71" spread="3.4"/>
                    <measurement group_id="O2" value="-14.08" spread="3.4"/>
                    <measurement group_id="O3" value="-13.04" spread="3.5"/>
                    <measurement group_id="O4" value="-10.68" spread="3.9"/>
                    <measurement group_id="O5" value="-12.86" spread="3.3"/>
                    <measurement group_id="O6" value="-7.62" spread="2.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;MIJ821 0.16 mg/kg weekly&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1082</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.09</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.37</ci_lower_limit>
            <ci_upper_limit>0.19</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;MIJ821 0.32 mg/kg weekly&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0993</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-5.42</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.83</ci_lower_limit>
            <ci_upper_limit>-0.02</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;MIJ821 0.16 mg/kg biweekly&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0598</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-6.46</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.78</ci_lower_limit>
            <ci_upper_limit>-1.15</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O4</group_id>
              <group_id>O6</group_id>
            </group_id_list>
            <groups_desc>Comparison of adjusted arithmetic mean: Mean Difference: &quot;MIJ821 0.32 mg/kg biweekly&quot; minus &quot;placebo&quot;.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2491</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>-3.06</param_value>
            <ci_percent>80</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.86</ci_lower_limit>
            <ci_upper_limit>2.74</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Young Mania Rating Scale</title>
        <description>To assess risk of mania induction. The Young Mania Rating Scale has 11 items and is based on the patient's subjective report of his/her clinical condition over the previous 48 hours. There are 4 items that are scored from 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior) and the remaining items are scored from 0 to 4. Higher scores indicate more severe mania.&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total YMRS score is 60. The range is 0 to 60 with the higher score indicating more severe symptoms.</description>
        <time_frame>Baseline, 24 hours, and 6 weeks (day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Young Mania Rating Scale</title>
          <description>To assess risk of mania induction. The Young Mania Rating Scale has 11 items and is based on the patient's subjective report of his/her clinical condition over the previous 48 hours. There are 4 items that are scored from 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior) and the remaining items are scored from 0 to 4. Higher scores indicate more severe mania.&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total YMRS score is 60. The range is 0 to 60 with the higher score indicating more severe symptoms.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.41" spread="0.5"/>
                    <measurement group_id="O2" value="-1.07" spread="0.5"/>
                    <measurement group_id="O3" value="-1.66" spread="0.5"/>
                    <measurement group_id="O4" value="-0.81" spread="0.5"/>
                    <measurement group_id="O5" value="-1.56" spread="0.5"/>
                    <measurement group_id="O6" value="-0.72" spread="0.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.28" spread="0.6"/>
                    <measurement group_id="O2" value="-2.13" spread="0.7"/>
                    <measurement group_id="O3" value="-0.65" spread="0.7"/>
                    <measurement group_id="O4" value="-1.55" spread="0.7"/>
                    <measurement group_id="O5" value="-1.80" spread="0.7"/>
                    <measurement group_id="O6" value="-0.92" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bech-Rafaelsen Melancholia Scale</title>
        <description>To assess efficacy in the melancholic subtype of depression. Depression scales are used primarily to measure changes, for example, to evaluate the efficacy of treatment with antidepressants. The Bech-Rafaelsen Melancholia Scale (BRMS) is a frequently used clinician rating scale to assess the severity of depression over the past 3 days. Each of the 11 BRMS items is operationally defined on a five-point scale (0-4); hence, the total score ranges from 0 to 44, higher scores indicating greater severity of depression.</description>
        <time_frame>Baseline, 24 hours, 48 hours and 6 weeks (Day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Bech-Rafaelsen Melancholia Scale</title>
          <description>To assess efficacy in the melancholic subtype of depression. Depression scales are used primarily to measure changes, for example, to evaluate the efficacy of treatment with antidepressants. The Bech-Rafaelsen Melancholia Scale (BRMS) is a frequently used clinician rating scale to assess the severity of depression over the past 3 days. Each of the 11 BRMS items is operationally defined on a five-point scale (0-4); hence, the total score ranges from 0 to 44, higher scores indicating greater severity of depression.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores 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="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at 24 hrs (n=11,10,10,8,9,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="8"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.9" spread="5.941"/>
                    <measurement group_id="O2" value="-9.5" spread="4.625"/>
                    <measurement group_id="O3" value="-7.9" spread="6.903"/>
                    <measurement group_id="O4" value="-8.1" spread="4.612"/>
                    <measurement group_id="O5" value="-7.7" spread="5.766"/>
                    <measurement group_id="O6" value="-6.0" spread="5.262"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-9.9" spread="5.326"/>
                    <measurement group_id="O2" value="-8.0" spread="5.185"/>
                    <measurement group_id="O3" value="-7.6" spread="8.383"/>
                    <measurement group_id="O4" value="-8.0" spread="5.508"/>
                    <measurement group_id="O5" value="-12.5" spread="7.853"/>
                    <measurement group_id="O6" value="-6.7" spread="6.659"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-8.6" spread="6.589"/>
                    <measurement group_id="O2" value="-8.6" spread="5.423"/>
                    <measurement group_id="O3" value="-7.6" spread="10.013"/>
                    <measurement group_id="O4" value="-6.0" spread="9.338"/>
                    <measurement group_id="O5" value="-8.9" spread="8.343"/>
                    <measurement group_id="O6" value="-6.9" spread="5.988"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Properties of MIJ821 in Plasma - Cmax (ng/mL)</title>
        <description>To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.</description>
        <time_frame>Day 1</time_frame>
        <population>PK analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>PK Properties of MIJ821 in Plasma - Cmax (ng/mL)</title>
          <description>To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.</description>
          <population>PK analysis set</population>
          <units>ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="99.5" spread="47.8"/>
                    <measurement group_id="O2" value="149" spread="63.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Properties of MIJ821 in Plasma - Tmax (ng/mL)</title>
        <description>To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.</description>
        <time_frame>Day 1</time_frame>
        <population>PK analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>PK Properties of MIJ821 in Plasma - Tmax (ng/mL)</title>
          <description>To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.</description>
          <population>PK analysis set</population>
          <units>hour</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.683" lower_limit="0.650" upper_limit="0.700"/>
                    <measurement group_id="O2" value="0.667" lower_limit="0.667" upper_limit="0.700"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)</title>
        <description>To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
        <time_frame>Day 1</time_frame>
        <population>PK analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)</title>
          <description>To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
          <population>PK analysis set</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="496" spread="239"/>
                    <measurement group_id="O2" value="738" spread="302"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)</title>
        <description>To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
        <time_frame>Day 1</time_frame>
        <population>PK analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>Pooled MIJ821 0.16 mg/kg</title>
            <description>Pooled MIJ821 0.16 mg/kg</description>
          </group>
          <group group_id="O2">
            <title>Pooled MIJ821 0.32 mg/kg</title>
            <description>Pooled MIJ821 0.32 mg/kg</description>
          </group>
        </group_list>
        <measure>
          <title>PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)</title>
          <description>To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.</description>
          <population>PK analysis set</population>
          <units>h*ng/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="13"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="462" spread="232"/>
                    <measurement group_id="O2" value="713" spread="275"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the CORE Melancholia Total Scale</title>
        <description>To assess efficacy in melancholic subtype of depression. This scale is an 18 item scale, with a 6 item component capturing cognitive impairment and two motoric scales capturing psychomotor retardation (7 items) and psychomotor agitation (5 items). A cut-off score of 8 or more has been shown to ifferentiate melancholic from non-melancholic depression, with higher scores representing a greater probability of melancholic depression. (Parker and McCraw 2017).&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total CORE Melancholia score is 54. The range is 0 to 54 with the higher score indicating more severe symptoms.</description>
        <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the CORE Melancholia Total Scale</title>
          <description>To assess efficacy in melancholic subtype of depression. This scale is an 18 item scale, with a 6 item component capturing cognitive impairment and two motoric scales capturing psychomotor retardation (7 items) and psychomotor agitation (5 items). A cut-off score of 8 or more has been shown to ifferentiate melancholic from non-melancholic depression, with higher scores representing a greater probability of melancholic depression. (Parker and McCraw 2017).&#xD;
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total CORE Melancholia score is 54. The range is 0 to 54 with the higher score indicating more severe symptoms.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 24 hrs (n=4,3,4,3,9,8)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="4"/>
                    <count group_id="O4" value="3"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.76" spread="2.9"/>
                    <measurement group_id="O2" value="-3.64" spread="3.6"/>
                    <measurement group_id="O3" value="-3.93" spread="3.0"/>
                    <measurement group_id="O4" value="1.38" spread="3.5"/>
                    <measurement group_id="O5" value="-5.07" spread="2.0"/>
                    <measurement group_id="O6" value="-3.61" spread="2.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 48 hrs (n=2,3,3,2,4,9)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.77" spread="3.9"/>
                    <measurement group_id="O2" value="-2.82" spread="3.7"/>
                    <measurement group_id="O3" value="-5.92" spread="3.2"/>
                    <measurement group_id="O4" value="1.62" spread="4.0"/>
                    <measurement group_id="O5" value="-6.68" spread="2.6"/>
                    <measurement group_id="O6" value="-5.06" spread="1.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at day 43 (n=3,2,3,2,8,8)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="3"/>
                    <count group_id="O4" value="2"/>
                    <count group_id="O5" value="8"/>
                    <count group_id="O6" value="8"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.79" spread="3.4"/>
                    <measurement group_id="O2" value="-4.82" spread="4.4"/>
                    <measurement group_id="O3" value="-7.24" spread="3.5"/>
                    <measurement group_id="O4" value="-6.49" spread="4.3"/>
                    <measurement group_id="O5" value="-9.01" spread="2.1"/>
                    <measurement group_id="O6" value="-5.21" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary of Adverse Events</title>
        <description>Summary of Adverse Events</description>
        <time_frame>Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.</time_frame>
        <population>safety analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Summary of Adverse Events</title>
          <description>Summary of Adverse Events</description>
          <population>safety analysis set</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="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs, subjects with AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="6"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Study drug-related AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="7"/>
                    <measurement group_id="O4" value="5"/>
                    <measurement group_id="O5" value="6"/>
                    <measurement group_id="O6" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="3"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs leading to discontinuation of study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Study drug-related AEs leading to discontinuation of study treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinician-Administered Dissociative States Scale</title>
        <description>To assess safety and tolerability, especially dissociative side effects. The Clinical-Administered Dissociative States Scale (CADSS) is a questionnaire that assesses dissociative effects. Each item is scored from 0 to 4 and individual scores are to be summed to obtain a total score ranging from a minimum of 0 to a maximum of 80. Higher scores represent a more severe condition.</description>
        <time_frame>Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Clinician-Administered Dissociative States Scale</title>
          <description>To assess safety and tolerability, especially dissociative side effects. The Clinical-Administered Dissociative States Scale (CADSS) is a questionnaire that assesses dissociative effects. Each item is scored from 0 to 4 and individual scores are to be summed to obtain a total score ranging from a minimum of 0 to a maximum of 80. Higher scores represent a more severe condition.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores 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="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change at 24 hrs (n=11,10,10,8,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="8"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.09" spread="5.262"/>
                    <measurement group_id="O2" value="1.10" spread="2.726"/>
                    <measurement group_id="O3" value="2.10" spread="3.414"/>
                    <measurement group_id="O4" value="3.00" spread="3.703"/>
                    <measurement group_id="O5" value="-0.50" spread="0.707"/>
                    <measurement group_id="O6" value="-0.25" spread="0.716"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.22" spread="0.667"/>
                    <measurement group_id="O2" value="0.50" spread="2.369"/>
                    <measurement group_id="O3" value="4.44" spread="10.394"/>
                    <measurement group_id="O4" value="3.14" spread="3.976"/>
                    <measurement group_id="O5" value="0.00" spread="0.00"/>
                    <measurement group_id="O6" value="-0.16" spread="0.375"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="1.927"/>
                    <measurement group_id="O2" value="0.00" spread="0.00"/>
                    <measurement group_id="O3" value="0.38" spread="1.061"/>
                    <measurement group_id="O4" value="1.00" spread="2.449"/>
                    <measurement group_id="O5" value="0.00" spread="1.118"/>
                    <measurement group_id="O6" value="-0.18" spread="0.636"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Dissociative Experiences Total Score</title>
        <description>The Dissociative Experiences Scale (DES) consists of twenty-eight questions about experiences the subject has experienced in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity.</description>
        <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Dissociative Experiences Total Score</title>
          <description>The Dissociative Experiences Scale (DES) consists of twenty-eight questions about experiences the subject has experienced in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.82" spread="1.0"/>
                    <measurement group_id="O2" value="2.00" spread="1.1"/>
                    <measurement group_id="O3" value="1.20" spread="1.1"/>
                    <measurement group_id="O4" value="7.22" spread="1.1"/>
                    <measurement group_id="O5" value="2.10" spread="1.1"/>
                    <measurement group_id="O6" value="2.50" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.80" spread="1.1"/>
                    <measurement group_id="O2" value="2.30" spread="1.1"/>
                    <measurement group_id="O3" value="1.89" spread="1.1"/>
                    <measurement group_id="O4" value="3.46" spread="1.2"/>
                    <measurement group_id="O5" value="1.89" spread="1.4"/>
                    <measurement group_id="O6" value="2.43" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.38" spread="1.1"/>
                    <measurement group_id="O2" value="1.61" spread="1.1"/>
                    <measurement group_id="O3" value="1.02" spread="1.1"/>
                    <measurement group_id="O4" value="0.24" spread="1.3"/>
                    <measurement group_id="O5" value="1.86" spread="1.1"/>
                    <measurement group_id="O6" value="2.63" spread="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Sheehan Suicidality Tracking Scale - (SSTS)</title>
        <description>Sheehan suicidality tracking scale(S-STS) is a fourteen-item (up to 22) scale. Each item in the S-STS is scored on a 5-point Likert scale (0=not at all, 1= a little, 2=moderately, 3=very, and 4=extremely). Data from the S-STS will be analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3 and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a and 8, plus score from item 5 if &gt;1). Higher scores represent a more severe condition.</description>
        <time_frame>Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Sheehan Suicidality Tracking Scale - (SSTS)</title>
          <description>Sheehan suicidality tracking scale(S-STS) is a fourteen-item (up to 22) scale. Each item in the S-STS is scored on a 5-point Likert scale (0=not at all, 1= a little, 2=moderately, 3=very, and 4=extremely). Data from the S-STS will be analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3 and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a and 8, plus score from item 5 if &gt;1). Higher scores represent a more severe condition.</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores 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="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Suicidal behavior subscale score - Change at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                    <measurement group_id="O2" value="0.00" spread="0.00"/>
                    <measurement group_id="O3" value="0.00" spread="0.00"/>
                    <measurement group_id="O4" value="0.11" spread="0.333"/>
                    <measurement group_id="O5" value="-0.10" spread="0.316"/>
                    <measurement group_id="O6" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal behavior subscale score - Change at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                    <measurement group_id="O2" value="0.00" spread="0.00"/>
                    <measurement group_id="O3" value="0.00" spread="0.00"/>
                    <measurement group_id="O4" value="0.00" spread="0.00"/>
                    <measurement group_id="O5" value="0.00" spread="0.00"/>
                    <measurement group_id="O6" value="0.00" spread="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal behavior subscale score - Change at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" spread="0.00"/>
                    <measurement group_id="O2" value="0.00" spread="0.00"/>
                    <measurement group_id="O3" value="0.00" spread="0.00"/>
                    <measurement group_id="O4" value="0.00" spread="0.00"/>
                    <measurement group_id="O5" value="-0.11" spread="0.333"/>
                    <measurement group_id="O6" value="0.12" spread="0.485"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal ideation subscale score - Change at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.45" spread="0.820"/>
                    <measurement group_id="O2" value="-0.50" spread="0.850"/>
                    <measurement group_id="O3" value="-0.30" spread="0.675"/>
                    <measurement group_id="O4" value="0.11" spread="1.269"/>
                    <measurement group_id="O5" value="-0.40" spread="0.966"/>
                    <measurement group_id="O6" value="-0.20" spread="0.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal ideation subscale score - Change at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.22" spread="0.667"/>
                    <measurement group_id="O2" value="-0.50" spread="0.850"/>
                    <measurement group_id="O3" value="-0.33" spread="0.707"/>
                    <measurement group_id="O4" value="-0.43" spread="0.787"/>
                    <measurement group_id="O5" value="0.00" spread="0.00"/>
                    <measurement group_id="O6" value="-0.16" spread="0.375"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal ideation subscale score - Change at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.38" spread="0.744"/>
                    <measurement group_id="O2" value="-0.13" spread="0.354"/>
                    <measurement group_id="O3" value="-0.13" spread="1.126"/>
                    <measurement group_id="O4" value="0.00" spread="1.265"/>
                    <measurement group_id="O5" value="-0.11" spread="1.269"/>
                    <measurement group_id="O6" value="0.12" spread="1.111"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SSTS total score - Change at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.45" spread="0.820"/>
                    <measurement group_id="O2" value="-0.50" spread="0.850"/>
                    <measurement group_id="O3" value="-0.30" spread="0.675"/>
                    <measurement group_id="O4" value="0.11" spread="1.764"/>
                    <measurement group_id="O5" value="-0.50" spread="1.269"/>
                    <measurement group_id="O6" value="-0.20" spread="0.523"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SSTS total score Change at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.22" spread="0.667"/>
                    <measurement group_id="O2" value="-0.50" spread="0.850"/>
                    <measurement group_id="O3" value="-0.33" spread="0.707"/>
                    <measurement group_id="O4" value="-0.57" spread="1.134"/>
                    <measurement group_id="O5" value="0.00" spread="0.00"/>
                    <measurement group_id="O6" value="-0.16" spread="0.375"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SSTS total score - Change at Day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.38" spread="0.744"/>
                    <measurement group_id="O2" value="-0.13" spread="0.354"/>
                    <measurement group_id="O3" value="-0.13" spread="1.126"/>
                    <measurement group_id="O4" value="-0.17" spread="1.602"/>
                    <measurement group_id="O5" value="-0.22" spread="1.563"/>
                    <measurement group_id="O6" value="0.47" spread="2.503"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Treatment Remissions (MADRS&lt;7)</title>
        <description>Percentage of Participants with treatment remissions as assessed via (MADRS&lt;7)</description>
        <time_frame>24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Treatment Remissions (MADRS&lt;7)</title>
          <description>Percentage of Participants with treatment remissions as assessed via (MADRS&lt;7)</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>% of participants with remission at 24 hrs (n=11,10,10,8,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="8"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.1"/>
                    <measurement group_id="O2" value="20.0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="11.1"/>
                    <measurement group_id="O5" value="20.0"/>
                    <measurement group_id="O6" value="5.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants with remission at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.2"/>
                    <measurement group_id="O2" value="10.0"/>
                    <measurement group_id="O3" value="11.1"/>
                    <measurement group_id="O4" value="28.6"/>
                    <measurement group_id="O5" value="25.0"/>
                    <measurement group_id="O6" value="10.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants with remission at Day 43 (n=8,8,8,6, 9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.0"/>
                    <measurement group_id="O2" value="37.5"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="16.7"/>
                    <measurement group_id="O5" value="22.2"/>
                    <measurement group_id="O6" value="11.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Total Hamilton Anxiety Scale</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
        <time_frame>Baseline, and at 6 weeks (day 43)</time_frame>
        <population>Intent-to-treat analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total Hamilton Anxiety Scale</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
          <population>Intent-to-treat analysis set</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="8"/>
                <count group_id="O6" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.94" spread="2.0"/>
                    <measurement group_id="O2" value="-5.69" spread="2.0"/>
                    <measurement group_id="O3" value="-7.17" spread="2.0"/>
                    <measurement group_id="O4" value="-3.83" spread="2.2"/>
                    <measurement group_id="O5" value="-4.93" spread="2.0"/>
                    <measurement group_id="O6" value="-4.80" spread="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline</title>
        <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
        <time_frame>Change from baseline at week 6 (Day 43)</time_frame>
        <population>Intent-to-treat analysis set</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline</title>
          <description>The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).</description>
          <population>Intent-to-treat analysis set</population>
          <units>Scores 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="8"/>
                <count group_id="O2" value="8"/>
                <count group_id="O3" value="8"/>
                <count group_id="O4" value="6"/>
                <count group_id="O5" value="8"/>
                <count group_id="O6" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.6" spread="6.927"/>
                    <measurement group_id="O2" value="-5.4" spread="4.565"/>
                    <measurement group_id="O3" value="-6.8" spread="6.606"/>
                    <measurement group_id="O4" value="-4.2" spread="9.432"/>
                    <measurement group_id="O5" value="-5.4" spread="7.763"/>
                    <measurement group_id="O6" value="-5.1" spread="5.651"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale</title>
        <description>The Koukopoulos Mixed Depression Rating Scale (KMDRS) assesses the excitatory or mixed nature in patients suffering from a Major Depressive Episode (MDE) as defined by DSM-5 criteria. This scale is meant to be used in conjunction with another scale that assess typical depression and anxiety symptoms. The scale contains 14 items to be evaluated by clinical assessment and patient interview on symptoms potentially experienced over the past week. Overall score increases with severity of symptoms and has a maximum score of 51. (Sani et al 2018).</description>
        <time_frame>Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)</time_frame>
        <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
        <group_list>
          <group group_id="O1">
            <title>MIJ821 0.16 mg/kg Weekly</title>
            <description>MIJ821 0.16 mg/kg weekly</description>
          </group>
          <group group_id="O2">
            <title>MIJ821 0.16 mg/kg Biweekly</title>
            <description>MIJ821 0.16 mg/kg biweekly</description>
          </group>
          <group group_id="O3">
            <title>MIJ821 0.32 mg/kg Weekly</title>
            <description>MIJ821 0.32 mg/kg weekly</description>
          </group>
          <group group_id="O4">
            <title>MIJ821 0.32 mg/kg Biweekly</title>
            <description>MIJ821 0.32 mg/kg biweekly</description>
          </group>
          <group group_id="O5">
            <title>Ketamine 0.5 mg/kg Weekly</title>
            <description>Ketamine 0.5 mg/kg weekly</description>
          </group>
          <group group_id="O6">
            <title>Placebo Weekly</title>
            <description>Placebo weekly</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale</title>
          <description>The Koukopoulos Mixed Depression Rating Scale (KMDRS) assesses the excitatory or mixed nature in patients suffering from a Major Depressive Episode (MDE) as defined by DSM-5 criteria. This scale is meant to be used in conjunction with another scale that assess typical depression and anxiety symptoms. The scale contains 14 items to be evaluated by clinical assessment and patient interview on symptoms potentially experienced over the past week. Overall score increases with severity of symptoms and has a maximum score of 51. (Sani et al 2018).</description>
          <population>Intent-to-treat analysis set. The number of participants analyzed varies from one visit to another because of missed visits and early terminations.</population>
          <units>Scores on a Scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="10"/>
                <count group_id="O4" value="9"/>
                <count group_id="O5" value="10"/>
                <count group_id="O6" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 24 hrs (n=11,10,10,9,10,20)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="11"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="10"/>
                    <count group_id="O4" value="9"/>
                    <count group_id="O5" value="10"/>
                    <count group_id="O6" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.79" spread="0.9"/>
                    <measurement group_id="O2" value="-2.38" spread="0.9"/>
                    <measurement group_id="O3" value="-1.50" spread="1.0"/>
                    <measurement group_id="O4" value="-2.46" spread="1.0"/>
                    <measurement group_id="O5" value="-1.28" spread="1.0"/>
                    <measurement group_id="O6" value="-2.33" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at 48 hrs (n=9,10,9,7,4,19)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="10"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="7"/>
                    <count group_id="O5" value="4"/>
                    <count group_id="O6" value="19"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.95" spread="1.0"/>
                    <measurement group_id="O2" value="-1.03" spread="0.9"/>
                    <measurement group_id="O3" value="-1.97" spread="1.0"/>
                    <measurement group_id="O4" value="-3.43" spread="1.1"/>
                    <measurement group_id="O5" value="0.01" spread="1.3"/>
                    <measurement group_id="O6" value="-1.97" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Adjusted arithmetic mean change from baseline at day 43 (n=8,8,8,6,9,17)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="8"/>
                    <count group_id="O3" value="8"/>
                    <count group_id="O4" value="6"/>
                    <count group_id="O5" value="9"/>
                    <count group_id="O6" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.18" spread="1.0"/>
                    <measurement group_id="O2" value="-1.06" spread="1.0"/>
                    <measurement group_id="O3" value="-1.55" spread="1.1"/>
                    <measurement group_id="O4" value="-2.04" spread="1.2"/>
                    <measurement group_id="O5" value="-1.68" spread="1.0"/>
                    <measurement group_id="O6" value="-1.59" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Responders (&gt;50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.</title>
        <description>Percentage of Participants who responded. The first mixed depression checklist, created by Koukopoulos, has 8 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then mixed depression would be diagnosed. The second mixed depression checklist, created by Angst, lists the 7 criteria for mania from DSM-5, which are marked as present or absent. If 3 or more criteria are marked present, excluding any duration criterion, then mixed depression would be diagnosed. The melancholia checklist, created by Ghaemi for this study, has 4 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then melancholia would be diagnosed.</description>
        <time_frame>24 hours, 48 hours, and 6 weeks (Day 43)</time_frame>
        <population>Intent-to-treat analysis set. The sampling size for this outcome measure was too small to support inferential statistics; therefore, the results for this outcome measure were limited to this high-level summary table, where data for the 2 drugs were pooled (MIJ821, all doses and all dosage regimes) and Ketamine vs placebo.</population>
        <group_list>
          <group group_id="O1">
            <title>Koukopoulos</title>
            <description>Koukopoulos Mixed Depression Rating Scale</description>
          </group>
          <group group_id="O2">
            <title>Angst</title>
            <description>Mixed depression checklist, created by Angst</description>
          </group>
          <group group_id="O3">
            <title>Ghaemi</title>
            <description>Melancholia checklist, created by Ghaemi</description>
          </group>
        </group_list>
        <measure>
          <title>Responders (&gt;50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.</title>
          <description>Percentage of Participants who responded. The first mixed depression checklist, created by Koukopoulos, has 8 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then mixed depression would be diagnosed. The second mixed depression checklist, created by Angst, lists the 7 criteria for mania from DSM-5, which are marked as present or absent. If 3 or more criteria are marked present, excluding any duration criterion, then mixed depression would be diagnosed. The melancholia checklist, created by Ghaemi for this study, has 4 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then melancholia would be diagnosed.</description>
          <population>Intent-to-treat analysis set. The sampling size for this outcome measure was too small to support inferential statistics; therefore, the results for this outcome measure were limited to this high-level summary table, where data for the 2 drugs were pooled (MIJ821, all doses and all dosage regimes) and Ketamine vs placebo.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
                <count group_id="O3" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>% of participants who responded at 24 hrs - drugs (n=5,5,5)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="5"/>
                    <count group_id="O2" value="5"/>
                    <count group_id="O3" value="5"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40.0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="20.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants who responded at 24 hrs - placebo (n=1,1,1)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                    <count group_id="O2" value="1"/>
                    <count group_id="O3" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants who responded at 48 hrs - drugs (N=6, 6, 6)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="6"/>
                    <count group_id="O2" value="6"/>
                    <count group_id="O3" value="6"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="33.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants who responded at 48 hrs - placebo (n=2,2,2)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                    <count group_id="O2" value="2"/>
                    <count group_id="O3" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="50.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants who responded at Day 43 - drugs (n=9,9,9)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="9"/>
                    <count group_id="O3" value="9"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.6"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="44.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>% of participants who responded at Day 43- placebo (n=3,3,3)</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                    <count group_id="O2" value="3"/>
                    <count group_id="O3" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33.3"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>MIJ821 0.16 mg/kg Weekly*</title>
          <description>MIJ821 0.16 mg/kg weekly*</description>
        </group>
        <group group_id="E2">
          <title>MIJ821 0.16 mg/kg Every Other Week</title>
          <description>MIJ821 0.16 mg/kg every other week</description>
        </group>
        <group group_id="E3">
          <title>MIJ821 0.32 mg/kg Weekly</title>
          <description>MIJ821 0.32 mg/kg weekly</description>
        </group>
        <group group_id="E4">
          <title>MIJ821 0.32 mg/kg Every Other Week</title>
          <description>MIJ821 0.32 mg/kg every other week</description>
        </group>
        <group group_id="E5">
          <title>Ketamine 0.5 mg/kg Weekly</title>
          <description>Ketamine 0.5 mg/kg weekly</description>
        </group>
        <group group_id="E6">
          <title>Placebo Weekly</title>
          <description>Placebo weekly</description>
        </group>
        <group group_id="E7">
          <title>Total</title>
          <description>Total</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (22.1)</default_vocab>
        <default_assessment>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="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="0" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="5" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Major depression</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Suicide threat</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Asthma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (22.1)</default_vocab>
        <default_assessment>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="7" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="6" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="37" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina pectoris</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperacusis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenopia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Photophobia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Vision blurred</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="4" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Frequent bowel movements</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="4" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="5" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Feeling abnormal</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Feeling of relaxation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Gait disturbance</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Oral herpes</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Poisoning deliberate</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Blood potassium decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Blood pressure increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Blood pressure systolic increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Amnesia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="10" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Ataxia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Disturbance in attention</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="10" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="6" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Hypoaesthesia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Memory impairment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Paraesthesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Sciatica</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="8" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Tunnel vision</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal dreams</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Daydreaming</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Depersonalisation/derealisation disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="5" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Disinhibition</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dissociation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Dissociative amnesia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Euphoric mood</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Illusion</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="3" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Mood swings</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Sleep disorder</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Sleep terror</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Time perception altered</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="2" subjects_at_risk="70"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="20"/>
                <counts group_id="E7" subjects_affected="1" subjects_at_risk="70"/>
              </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>The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Study Director</name_or_title>
      <organization>Novartis Pharmaceuticals</organization>
      <phone>+ 1 862 778 8300</phone>
      <email>Novartis.email@Novartis.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/NCT03756129
org study id: CMIJ821X2201
nct id: NCT03756129
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study evaluated the efficacy and safety of the compound MIJ821 compared to placebo in
      patients aged from 18 to 65 years diagnosed with treatment-resistant depression. The study
      was conducted in the US and in Europe (Spain). The MIJ821 was administered via infusion on a
      weekly or bi-weekly basis. The efficacy was measured after 24 hours using a specific golden
      standard scale, the Montgomery-Asberg Depression Rating Scale. The study duration was 6 weeks
      of treatment plus 1 month of follow up period.
This was a non-confirmatory, multi-center, 6-treatment arm in European (Spain) and
      5-treatment arm in the US (no ketamine arm), randomized, subject and investigator blinded,
      parallel-group, placebo-controlled study in patients with treatment-resistant depression. The
      total duration for each subject in the study was maximum 14 weeks: a screening period of
      maximum 4 weeks, a 36-day treatment period and a 5-week follow-up period.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This is a non-confirmatory, multi-center, 6-treatment arm in the EU countries and 5-treatment arm in the USA (no ketamine arm), randomized, subject and investigator blinded, parallel group, placebo controlled study in treatment-resistant depression patients. The study allows for the inclusion of subjects seeking treatment for their disease from both an 'inpatient' or 'outpatient' clinic setting.
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 24 Hrs
time frame: Baseline, and at 24 hours
description: Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at 48 Hrs
time frame: Baseline, and at 48 hours
description: Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
measure: Change From Baseline in the Total Score of the Montgomery Asberg Depression Rating Scale (MADRS) at Week 6
time frame: Baseline, and at Week 6
description: Efficacy. To assess change from baseline in the total MADRS score. The efficacy of MIJ821 in treatment-resistant depression will be compared to the placebo after single dose administration. MADRS is a clinician-rated scale designed to measure depression severity and detects changes due to antidepressant treatment: the test consists of 10 items, each of which is scored from 0 (item not present or normal) to 6 (severe or continuous presence of the symptoms), for a total possible score of 60. Higher scores represent a more severe condition.
measure: Change From Baseline in the Young Mania Rating Scale
time frame: Baseline, 24 hours, and 6 weeks (day 43)
description: To assess risk of mania induction. The Young Mania Rating Scale has 11 items and is based on the patient's subjective report of his/her clinical condition over the previous 48 hours. There are 4 items that are scored from 0 to 8 (irritability, speech, thought content, and disruptive/aggressive behavior) and the remaining items are scored from 0 to 4. Higher scores indicate more severe mania.
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total YMRS score is 60. The range is 0 to 60 with the higher score indicating more severe symptoms.
measure: Bech-Rafaelsen Melancholia Scale
time frame: Baseline, 24 hours, 48 hours and 6 weeks (Day 43)
description: To assess efficacy in the melancholic subtype of depression. Depression scales are used primarily to measure changes, for example, to evaluate the efficacy of treatment with antidepressants. The Bech-Rafaelsen Melancholia Scale (BRMS) is a frequently used clinician rating scale to assess the severity of depression over the past 3 days. Each of the 11 BRMS items is operationally defined on a five-point scale (0-4); hence, the total score ranges from 0 to 44, higher scores indicating greater severity of depression.
measure: PK Properties of MIJ821 in Plasma - Cmax (ng/mL)
time frame: Day 1
description: To assess MIJ821 pharmacokinetics in plasma described by Cmax. A single, sparse PK measurement was taken on Day 1.
measure: PK Properties of MIJ821 in Plasma - Tmax (ng/mL)
time frame: Day 1
description: To assess MIJ821 pharmacokinetics in plasma described by Tmax. A single, sparse PK measurement was taken on Day 1.
measure: PK Properties of MIJ821 in Plasma - AUClast (h*ng/mL)
time frame: Day 1
description: To assess MIJ821 pharmacokinetics in plasma described by AUClast (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
measure: PK Properties of MIJ821 in Plasma - AUC0-24h (h*ng/mL)
time frame: Day 1
description: To assess MIJ821 pharmacokinetics in plasma described by AUC0-24h (h*ng/mL). A single, sparse PK measurement was taken on Day 1.
measure: Change From Baseline in the CORE Melancholia Total Scale
time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
description: To assess efficacy in melancholic subtype of depression. This scale is an 18 item scale, with a 6 item component capturing cognitive impairment and two motoric scales capturing psychomotor retardation (7 items) and psychomotor agitation (5 items). A cut-off score of 8 or more has been shown to ifferentiate melancholic from non-melancholic depression, with higher scores representing a greater probability of melancholic depression. (Parker and McCraw 2017).
The total clinical score was calculated as the summation of the individual subscale scores. The maximum for the total CORE Melancholia score is 54. The range is 0 to 54 with the higher score indicating more severe symptoms.
measure: Summary of Adverse Events
time frame: Adverse events were reported from first dose of study treatment until end of study treatment plus 30 post treatment, up to a maximum duration of 66 days.
description: Summary of Adverse Events
measure: Clinician-Administered Dissociative States Scale
time frame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
description: To assess safety and tolerability, especially dissociative side effects. The Clinical-Administered Dissociative States Scale (CADSS) is a questionnaire that assesses dissociative effects. Each item is scored from 0 to 4 and individual scores are to be summed to obtain a total score ranging from a minimum of 0 to a maximum of 80. Higher scores represent a more severe condition.
measure: Change From Baseline in the Dissociative Experiences Total Score
time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
description: The Dissociative Experiences Scale (DES) consists of twenty-eight questions about experiences the subject has experienced in his/her daily life. The subject determines to what degree he/she has been facing the situation by selecting a percentage from 0% (never) to 100% (always), with 10% increments in between. Higher scores mean higher severity.
measure: Sheehan Suicidality Tracking Scale - (SSTS)
time frame: Change from baseline at 24 hours, 48 hours, and 6 weeks (Day 43)
description: Sheehan suicidality tracking scale(S-STS) is a fourteen-item (up to 22) scale. Each item in the S-STS is scored on a 5-point Likert scale (0=not at all, 1= a little, 2=moderately, 3=very, and 4=extremely). Data from the S-STS will be analyzed as individual item scores, suicidal ideation subscale score (sum of scores from items 2, 3 and 4, plus score from item 5 if ≤1), suicidal behavior subscale score (sum of scores from items 6, 7a and 8, plus score from item 5 if >1). Higher scores represent a more severe condition.
measure: Percentage of Participants With Treatment Remissions (MADRS<7)
time frame: 24 hours, 48 hours, and 6 weeks (Day 43)
description: Percentage of Participants with treatment remissions as assessed via (MADRS<7)
measure: Change From Baseline in the Total Hamilton Anxiety Scale
time frame: Baseline, and at 6 weeks (day 43)
description: The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).
measure: Summary Statistics of Total Hamilton Anxiety Scale - Change From Baseline
time frame: Change from baseline at week 6 (Day 43)
description: The Hamilton Anxiety Rating Scale (HAM-A) measures psychic anxiety and somatic anxiety symptoms based on a clinical assessment and patient interview. The scale has 14 items, with each item rated from 0-4, ranging from not present to very severe. A maximum score of 56 indicates the most severe case. (Hamilton 1959).
measure: Change From Baseline in the Total Koukopoulos Mixed Depression Rating Scale
time frame: Baseline, 24 hours, 48 hrs, and 6 weeks (day 43)
description: The Koukopoulos Mixed Depression Rating Scale (KMDRS) assesses the excitatory or mixed nature in patients suffering from a Major Depressive Episode (MDE) as defined by DSM-5 criteria. This scale is meant to be used in conjunction with another scale that assess typical depression and anxiety symptoms. The scale contains 14 items to be evaluated by clinical assessment and patient interview on symptoms potentially experienced over the past week. Overall score increases with severity of symptoms and has a maximum score of 51. (Sani et al 2018).
measure: Responders (>50% Improvement in Bech-Rafaelsen Melancholia Scale) and Melancholia and Mixed Depression Checklist Factor.
time frame: 24 hours, 48 hours, and 6 weeks (Day 43)
description: Percentage of Participants who responded. The first mixed depression checklist, created by Koukopoulos, has 8 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then mixed depression would be diagnosed. The second mixed depression checklist, created by Angst, lists the 7 criteria for mania from DSM-5, which are marked as present or absent. If 3 or more criteria are marked present, excluding any duration criterion, then mixed depression would be diagnosed. The melancholia checklist, created by Ghaemi for this study, has 4 criteria, which are marked as present or absent. If 3 or more criteria are marked present, then melancholia would be diagnosed.
arm group label: MIJ821 low dose weekly
arm group type: Experimental
description: Infusion. MIJ821 low dose weekly - 0.16 mg/kg
arm group label: MIJ821 low dose bi-weekly
arm group type: Experimental
description: Infusion. MIJ821 low dose bi-weekly - 0.16 mg/kg
arm group label: MIJ821 high dose weekly
arm group type: Experimental
description: Infusion. MIJ821 high dose weekly - 0.32 mg/kg
arm group label: MIJ821 high dose bi-weekly
arm group type: Experimental
description: Infusion. MIJ821 high dose bi-weekly - 0.32 mg/kg
arm group label: Placebo weekly
arm group type: Placebo Comparator
description: Infusion. Placebo weekly
arm group label: Ketamine 0.5 mg/kg weekly
arm group type: Active Comparator
description: Infusion. Ketamine 0.5 mg/kg weekly
intervention type: Drug
intervention name: MIJ821
description: Different dosages and different regimen for MIJ821
arm group label: MIJ821 high dose bi-weekly
arm group label: MIJ821 high dose weekly
arm group label: MIJ821 low dose bi-weekly
arm group label: MIJ821 low dose weekly
intervention type: Drug
intervention name: Placebo
description: Infusion
arm group label: Placebo weekly
intervention type: Drug
intervention name: Ketamine
description: Infusion
arm group label: Ketamine 0.5 mg/kg weekly
other name: Ketamine dose to be capped at 40 mg/day for patients over 80 kg
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
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country: Spain
country: United States
url: https://www.novctrd.com/ctrdweb/patientsummary/patientsummaries?patientSummaryId=721
description: A Plain Language Trial Summary is available on novartisclinicaltrials.com
responsible party type: Sponsor
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Treatment-Resistant
mesh term: Ketamine
sharing ipd: Yes
ipd description: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com.
ipd url: https://www.clinicalstudydatarequest.com/
provided document: 
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