<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/NCT04476030</url>
  </required_header>
  <id_info>
    <org_study_id>217-MDD-305</org_study_id>
    <nct_id>NCT04476030</nct_id>
  </id_info>
  <brief_title>A Comparative Study of Sage-217 Plus an Antidepressant (ADT) Versus Placebo Plus an ADT in Adults With Major Depressive Disorder</brief_title>
  <official_title>A Phase 3, Randomized, Double-Blind Study Comparing the Efficacy and Safety of SAGE-217 Plus an Antidepressant Versus Placebo Plus an Antidepressant in Adults With Major Depressive Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sage Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sage Therapeutics</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this study is to evaluate the efficacy of SAGE-217 plus an ADT in the&#xD;
      treatment of major depressive disorder (MDD) compared to placebo plus an ADT.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 16, 2020</start_date>
  <completion_date type="Actual">November 30, 2021</completion_date>
  <primary_completion_date type="Actual">November 30, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 3</measure>
    <time_frame>Baseline and Day 3</time_frame>
    <description>HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in 17-item HAM-D Total Score over the Blinded Treatment Period Using Equal Weights for the Scheduled Visits</measure>
    <time_frame>Baseline, Days 3, 8, 12, and 15</time_frame>
    <description>HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in 17-item HAM-D Total Score at Days 15 and 42</measure>
    <time_frame>Baseline, Days 15 and 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in 17-item HAM-D Total Score Around the End of Blinded Treatment Using Equal Weights for the Scheduled Visits</measure>
    <time_frame>Baseline, Days 12, 15, and 18</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with HAM-D Response</measure>
    <time_frame>Days 15 and 42</time_frame>
    <description>HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with HAM-D Remission</measure>
    <time_frame>Days 15 and 42</time_frame>
    <description>HAM-D remission is defined as having a HAM-D total score of ≤7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Clinical Global Impression - Severity (CGI-S) Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment. Severity of mental illness is assessed using ratings as 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Clinical Global Impression - Improvement (CGI-I) Response</measure>
    <time_frame>Days 3 and 15</time_frame>
    <description>CGI-I response will be defined as having a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I employs a 7-point Likert scale to measure the overall improvement (whether or not due entirely to drug treatment) in participant's condition posttreatment. Response choices include: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item has a score range of 0 to 6. MADRS total score (ranging from 0 to 60) will be sum of the 10 individual item scores. The higher MADRS scores indicate more severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with MADRS Response</measure>
    <time_frame>Day 15</time_frame>
    <description>MADRS response is defined as having a 50% or greater reduction from baseline in MADRS total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with MADRS Remission</measure>
    <time_frame>Day 15</time_frame>
    <description>MADRS remission is defined as having a MADRS total score of ≤10.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>14-item HAM-A will be used to rate the severity of symptoms of anxiety. HAM-A total score will be the sum of the 14 individual item scores. Each of the 14 items measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scores of 0 (not present) to 4 (very severe) are assigned, with a total score range of 0 to 56, where &lt;17 = mild severity, 18 to 24 = mild to moderate severity, and 25 to 30 = moderate to severe severity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First HAM-D Response</measure>
    <time_frame>Up to Day 42</time_frame>
    <description>HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Depressive Symptoms Assessed by 9-item Patient Health Questionnaire (PHQ-9)</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>PHQ-9 is a participant-rated depressive symptom severity scale consisting of 9 individual items. Scoring is based on responses to specific questions, as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. PHQ-9 total score will be the sum of the 9 individual item scores, where, 0 to 4 = minimal depression, 5 to 9 = mild depression, 10 to 14 = moderate depression, 15 to 19 = moderately severe depression; and 20 to 27 = severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)</measure>
    <time_frame>Up to Day 42</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants with TEAEs, Graded by Severity</measure>
    <time_frame>Up to Day 42</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">440</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive SAGE-217 capsules, orally, daily with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily for up to 42 days, with fat-containing food.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive SAGE-217-matching placebo capsules, orally, daily with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily for up to 42 days, with fat-containing food.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAGE-217</intervention_name>
    <description>Oral capsules</description>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Matching Placebo</intervention_name>
    <description>Oral capsules</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sertraline</intervention_name>
    <description>Oral tablets</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Escitalopram</intervention_name>
    <description>Oral tablets</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Citalopram</intervention_name>
    <description>Oral tablets</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Duloxetine</intervention_name>
    <description>Oral capsules</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Desvenlafaxine</intervention_name>
    <description>Oral tablets</description>
    <arm_group_label>Active Comparator: Placebo + Assigned ADT</arm_group_label>
    <arm_group_label>Experimental: SAGE-217 + Assigned ADT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of MDD as diagnosed by Structured Clinical Interview for Diagnostic and&#xD;
             Statistical Manual of Mental Disorders, Fifth Edition Clinical Trials Version&#xD;
             (SCID-5-CT), with symptoms that have been present for at least a 4-week period&#xD;
&#xD;
          -  HAM-D-17 total score of ≥24 at Screening and Day 1&#xD;
&#xD;
          -  Participant in good physical health and has no clinically significant findings, as&#xD;
             determined by the investigator, on physical examination, 12-lead electrocardiogram&#xD;
             (ECG), or clinical laboratory tests&#xD;
&#xD;
          -  Participant is willing, able, and eligible to take at least 1 of the 5 ADTs specified&#xD;
             in the protocol (an eligible ADT is an ADT that has not been taken during the current&#xD;
             depressive episode and for which the participant has no contraindications; further, a&#xD;
             participant is not eligible for citalopram if escitalopram has been taken during the&#xD;
             current depressive episode, and vice versa)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has attempted suicide associated with the current episode of MDD&#xD;
&#xD;
          -  Participant had onset of the current depressive episode during pregnancy or 4 weeks&#xD;
             postpartum, or the participant has presented for screening during the 6-month&#xD;
             postpartum period&#xD;
&#xD;
          -  Participant has treatment-resistant depression&#xD;
&#xD;
          -  History of bipolar disorder, schizophrenia, and/or schizoaffective disorder&#xD;
&#xD;
          -  Known allergy to SAGE-217, allopregnanolone, or related compounds&#xD;
&#xD;
          -  Has taken antidepressants within 30 days prior to Day 1, and/or has taken fluoxetine&#xD;
             within 60 days prior to Day 1&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>64 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Dothan</city>
        <state>Alabama</state>
        <zip>36303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92626</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Los Alamitos</city>
        <state>California</state>
        <zip>90720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Riverside</city>
        <state>California</state>
        <zip>92503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Temecula</city>
        <state>California</state>
        <zip>92591</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80910</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Cromwell</city>
        <state>Connecticut</state>
        <zip>06416</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Norwich</city>
        <state>Connecticut</state>
        <zip>06360</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Coral Springs</city>
        <state>Florida</state>
        <zip>33067</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32256</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32807</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Pensacola</city>
        <state>Florida</state>
        <zip>32502</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Alpharetta</city>
        <state>Georgia</state>
        <zip>30022</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30331</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Savannah</city>
        <state>Georgia</state>
        <zip>31405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60634</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Watertown</city>
        <state>Massachusetts</state>
        <zip>02472</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Ann Arbor</city>
        <state>Michigan</state>
        <zip>48109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Saint Charles</city>
        <state>Missouri</state>
        <zip>63304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Lincoln</city>
        <state>Nebraska</state>
        <zip>68526</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Cherry Hill</city>
        <state>New Jersey</state>
        <zip>08002</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Marlton</city>
        <state>New Jersey</state>
        <zip>08053</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Princeton</city>
        <state>New Jersey</state>
        <zip>08540</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Mount Kisco</city>
        <state>New York</state>
        <zip>10549</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Beachwood</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45212</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>North Canton</city>
        <state>Ohio</state>
        <zip>44720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Plymouth Meeting</city>
        <state>Pennsylvania</state>
        <zip>19462</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78759</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77081</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Wichita Falls</city>
        <state>Texas</state>
        <zip>76309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Bellevue</city>
        <state>Washington</state>
        <zip>98007</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <disposition_first_submitted>November 30, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>November 30, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">December 5, 2022</disposition_first_posted>
  <last_update_submitted>November 30, 2022</last_update_submitted>
  <last_update_submitted_qc>November 30, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 5, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>MDD</keyword>
  <keyword>SAGE-217</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Duloxetine Hydrochloride</mesh_term>
    <mesh_term>Citalopram</mesh_term>
    <mesh_term>Sertraline</mesh_term>
    <mesh_term>Desvenlafaxine Succinate</mesh_term>
    <mesh_term>Escitalopram</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.</ipd_description>
  </patient_data>
  <pending_results>
    <submitted>August 25, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted, but a results disposition has been submitted           -->
</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/NCT04476030
org study id: 217-MDD-305
nct id: NCT04476030
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary purpose of this study is to evaluate the efficacy of SAGE-217 plus an ADT in the
      treatment of major depressive disorder (MDD) compared to placebo plus an ADT.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change from Baseline in 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 3
time frame: Baseline and Day 3
description: HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.
measure: Change from Baseline in 17-item HAM-D Total Score over the Blinded Treatment Period Using Equal Weights for the Scheduled Visits
time frame: Baseline, Days 3, 8, 12, and 15
description: HAM-D total score will be the sum of the 17 individual item scores. Items with score range of 0 to 2 include insomnia (early, middle, late), somatic symptoms (gastrointestinal and general), genital symptoms, loss of weight, and insight. Items with score range of 2 to 4 include agitation, depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, work and activities, retardation (slowness of thought and speech; impaired ability to concentrate; decreased motor activity), anxiety (psychic and somatic), and hypochondriasis. The total score ranges from 0 to 52, where higher score indicates more depression.
measure: Change from Baseline in 17-item HAM-D Total Score at Days 15 and 42
time frame: Baseline, Days 15 and 42
measure: Change from Baseline in 17-item HAM-D Total Score Around the End of Blinded Treatment Using Equal Weights for the Scheduled Visits
time frame: Baseline, Days 12, 15, and 18
measure: Percentage of Participants with HAM-D Response
time frame: Days 15 and 42
description: HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.
measure: Percentage of Participants with HAM-D Remission
time frame: Days 15 and 42
description: HAM-D remission is defined as having a HAM-D total score of ≤7.
measure: Change from Baseline in Clinical Global Impression - Severity (CGI-S) Score
time frame: Baseline and Day 15
description: CGI-S uses a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment. Severity of mental illness is assessed using ratings as 1 = normal, not at all ill; 2 = borderline mentally ill; 3 = mildly ill; 4 = moderately ill; 5 = markedly ill; 6 = severely ill; and 7 = extremely ill.
measure: Percentage of Participants with Clinical Global Impression - Improvement (CGI-I) Response
time frame: Days 3 and 15
description: CGI-I response will be defined as having a CGI-I score of 1 (very much improved) or 2 (much improved). CGI-I employs a 7-point Likert scale to measure the overall improvement (whether or not due entirely to drug treatment) in participant's condition posttreatment. Response choices include: 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
measure: Change from Baseline in Montgomery-Åsberg Depression Rating Scale (MADRS) Total Score
time frame: Baseline and Day 15
description: MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item has a score range of 0 to 6. MADRS total score (ranging from 0 to 60) will be sum of the 10 individual item scores. The higher MADRS scores indicate more severe depression.
measure: Percentage of Participants with MADRS Response
time frame: Day 15
description: MADRS response is defined as having a 50% or greater reduction from baseline in MADRS total score.
measure: Percentage of Participants with MADRS Remission
time frame: Day 15
description: MADRS remission is defined as having a MADRS total score of ≤10.
measure: Change from Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score
time frame: Baseline and Day 15
description: 14-item HAM-A will be used to rate the severity of symptoms of anxiety. HAM-A total score will be the sum of the 14 individual item scores. Each of the 14 items measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). Scores of 0 (not present) to 4 (very severe) are assigned, with a total score range of 0 to 56, where <17 = mild severity, 18 to 24 = mild to moderate severity, and 25 to 30 = moderate to severe severity.
measure: Time to First HAM-D Response
time frame: Up to Day 42
description: HAM-D response is defined as having a 50% or greater reduction from baseline in HAM-D total score.
measure: Change from Baseline in Depressive Symptoms Assessed by 9-item Patient Health Questionnaire (PHQ-9)
time frame: Baseline and Day 15
description: PHQ-9 is a participant-rated depressive symptom severity scale consisting of 9 individual items. Scoring is based on responses to specific questions, as follows: 0 = not at all; 1 = several days; 2 = more than half the days; and 3 = nearly every day. PHQ-9 total score will be the sum of the 9 individual item scores, where, 0 to 4 = minimal depression, 5 to 9 = mild depression, 10 to 14 = moderate depression, 15 to 19 = moderately severe depression; and 20 to 27 = severe depression.
measure: Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)
time frame: Up to Day 42
measure: Percentage of Participants with TEAEs, Graded by Severity
time frame: Up to Day 42
arm group label: Experimental: SAGE-217 + Assigned ADT
arm group type: Experimental
description: Participants will receive SAGE-217 capsules, orally, daily with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily for up to 42 days, with fat-containing food.
arm group label: Active Comparator: Placebo + Assigned ADT
arm group type: Active Comparator
description: Participants will receive SAGE-217-matching placebo capsules, orally, daily with an assigned ADT (sertraline, escitalopram, citalopram, duloxetine, or desvenlafaxine administered per labeled prescribing information), daily from Day 1 through 14, followed by the same ADT, per labeled prescribing information, daily for up to 42 days, with fat-containing food.
intervention type: Drug
intervention name: SAGE-217
description: Oral capsules
arm group label: Experimental: SAGE-217 + Assigned ADT
intervention type: Drug
intervention name: Matching Placebo
description: Oral capsules
arm group label: Active Comparator: Placebo + Assigned ADT
intervention type: Drug
intervention name: Sertraline
description: Oral tablets
arm group label: Active Comparator: Placebo + Assigned ADT
arm group label: Experimental: SAGE-217 + Assigned ADT
intervention type: Drug
intervention name: Escitalopram
description: Oral tablets
arm group label: Active Comparator: Placebo + Assigned ADT
arm group label: Experimental: SAGE-217 + Assigned ADT
intervention type: Drug
intervention name: Citalopram
description: Oral tablets
arm group label: Active Comparator: Placebo + Assigned ADT
arm group label: Experimental: SAGE-217 + Assigned ADT
intervention type: Drug
intervention name: Duloxetine
description: Oral capsules
arm group label: Active Comparator: Placebo + Assigned ADT
arm group label: Experimental: SAGE-217 + Assigned ADT
intervention type: Drug
intervention name: Desvenlafaxine
description: Oral tablets
arm group label: Active Comparator: Placebo + Assigned ADT
arm group label: Experimental: SAGE-217 + Assigned ADT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 64 Years
healthy volunteers: No
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country: United States
responsible party type: Sponsor
mesh term: Depressive Disorder
mesh term: Depression
mesh term: Depressive Disorder, Major
mesh term: Duloxetine Hydrochloride
mesh term: Citalopram
mesh term: Sertraline
mesh term: Desvenlafaxine Succinate
mesh term: Escitalopram
sharing ipd: No
ipd description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
submitted: August 25, 2023