<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/NCT04442490</url>
  </required_header>
  <id_info>
    <org_study_id>217-MDD-301B</org_study_id>
    <nct_id>NCT04442490</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Efficacy of Sage-217 in the Treatment of Adult Participants With Major Depressive Disorder (MDD)</brief_title>
  <official_title>A Phase 3, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study Evaluating the Efficacy of SAGE-217 in the Treatment of Adult Subjects 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 purpose of this study to evaluate the efficacy of SAGE-217 in the treatment of&#xD;
      participants with MDD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 7, 2020</start_date>
  <completion_date type="Actual">April 21, 2021</completion_date>
  <primary_completion_date type="Actual">March 26, 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 the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Severity (CGI-S) Score</measure>
    <time_frame>Day 15</time_frame>
    <description>The CGI-S is a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HAM-D Total Score</measure>
    <time_frame>Baseline and Days 3, 28, and 42</time_frame>
    <description>The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With HAM-D Response</measure>
    <time_frame>Days 15 and 42</time_frame>
    <description>The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.</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 HAM-D total score ≤7.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response</measure>
    <time_frame>Day 15</time_frame>
    <description>CGI-I response is defined as having a CGI-I score of &quot;very much improved&quot; or &quot;much improved.&quot; The CGI-I employs a 7-point Likert scale to measure the overall improvement in the 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>Montgomery Åsberg Depression Rating Scale (MADRS) Total Score</measure>
    <time_frame>Day 15</time_frame>
    <description>The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hamilton Rating Scale for Anxiety (HAM-A) Total Score</measure>
    <time_frame>Day 15</time_frame>
    <description>The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to First HAM-D Response</measure>
    <time_frame>Days 1, 3, 8, 12, 15, 21, 28, 35 and 42</time_frame>
    <description>The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in PRO Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form version 2 (SF-36v2) Score</measure>
    <time_frame>Baseline and Days 1, 8, 15, 28 and 42</time_frame>
    <description>Participant's health will be assessed using Patient-reported outcome (PRO) health related quality of life (HRQOL) SF-36 V2. The SF-36v2 is a 36-item measure including eight health dimensions which are four physical health status domains and four mental health status domains. Scores on each item are summed and averaged (range = 0 &quot;worst&quot;-100 &quot;best&quot;). Higher SF-36v2 scores will indicate a better state of health.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score</measure>
    <time_frame>Baseline and Days 1, 8, 15, 28 and 42</time_frame>
    <description>The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">543</enrollment>
  <condition>Depressive Disorder, Major</condition>
  <arm_group>
    <arm_group_label>SAGE-217</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive SAGE-217 capsules, once daily for 14 days. The dose may be decreased based on safety and tolerability.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAGE-217 Matched Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive SAGE-217 matched-placebo capsules, once daily for 14 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAGE-217</intervention_name>
    <description>SAGE-217 oral capsules.</description>
    <arm_group_label>SAGE-217</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>SAGE-217 matched-placebo oral capsules.</description>
    <arm_group_label>SAGE-217 Matched Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant with diagnosis of MDD as diagnosed by Structured Clinical Interview for&#xD;
             Diagnostic and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition&#xD;
             (DSM-5) Clinical Trial Version [SCID-5-CT], with symptoms that have been present for&#xD;
             at least a 4-week period.&#xD;
&#xD;
          2. Participant has a Hamilton Rating Scale for Depression (HAM-D) total score ≥24 at&#xD;
             screening and Day 1 (prior to dosing).&#xD;
&#xD;
          3. Participants taking antidepressants must have been taking these medications at the&#xD;
             same dose for at least 60 days prior to Day 1. Participants who have stopped taking&#xD;
             antidepressants within 60 days must have stopped for longer than 5 half-lives of the&#xD;
             antidepressant prior to Day 1. Participants receiving psychotherapy must have been&#xD;
             receiving therapy on a regular schedule for at least 60 days prior to Day 1.&#xD;
&#xD;
          4. Participant is willing to delay start of other antidepressant or antianxiety&#xD;
             medications and any new pharmacotherapy regimens, including as-needed benzodiazepine&#xD;
             anxiolytics and sleep aids, until after completion of the Day 42 visit.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participant is currently at significant risk of suicide, as judged by the&#xD;
             Investigator, or has attempted suicide associated with the current episode of MDD.&#xD;
&#xD;
          2. Participant has 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;
          3. Participant has a body mass index (BMI) ≤18 or ≥45 kg/m^2 at Screening, which is&#xD;
             subject to a broader evaluation of medical comorbidities.&#xD;
&#xD;
          4. Participant has treatment-resistant depression, defined as persistent depressive&#xD;
             symptoms despite treatment with adequate doses of antidepressants within the current&#xD;
             major depressive episode (excluding antipsychotics) from two different classes for at&#xD;
             least 4 weeks of treatment.&#xD;
&#xD;
          5. Participant has a medical history of seizures, bipolar disorder, schizophrenia, and/or&#xD;
             schizoaffective disorder.&#xD;
&#xD;
          6. Participant has a history of mild, moderate, or severe substance use disorder&#xD;
             (including benzodiazepines) diagnosed using DSM-5 criteria in the 12 months prior to&#xD;
             screening.&#xD;
&#xD;
          7. Participant is taking psychostimulants (eg, methylphenidate, amphetamine) or opioids,&#xD;
             regularly or as-needed, at Day -28.&#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>Rogers</city>
        <state>Arkansas</state>
        <zip>72758</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Bellflower</city>
        <state>California</state>
        <zip>90706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Garden Grove</city>
        <state>California</state>
        <zip>92845</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>Lemon Grove</city>
        <state>California</state>
        <zip>91945</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>Pico Rivera</city>
        <state>California</state>
        <zip>90660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Redlands</city>
        <state>California</state>
        <zip>92374</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>Sherman Oaks</city>
        <state>California</state>
        <zip>91403</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>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>Hollywood</city>
        <state>Florida</state>
        <zip>33024</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>Lauderhill</city>
        <state>Florida</state>
        <zip>33319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</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>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>30328</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>Decatur</city>
        <state>Georgia</state>
        <zip>30030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Flowood</city>
        <state>Mississippi</state>
        <zip>39232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>O'Fallon</city>
        <state>Missouri</state>
        <zip>63368</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89102</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>Charlotte</city>
        <state>North Carolina</state>
        <zip>28211</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>Dayton</city>
        <state>Ohio</state>
        <zip>45417</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>Portland</city>
        <state>Oregon</state>
        <zip>97210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Allentown</city>
        <state>Pennsylvania</state>
        <zip>18104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>DeSoto</city>
        <state>Texas</state>
        <zip>75115</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>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>June 18, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 22, 2020</study_first_posted>
  <disposition_first_submitted>March 25, 2022</disposition_first_submitted>
  <disposition_first_submitted_qc>March 25, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 29, 2022</disposition_first_posted>
  <last_update_submitted>March 25, 2022</last_update_submitted>
  <last_update_submitted_qc>March 25, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Depression</keyword>
  <keyword>Depressive disorder</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>
  <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/NCT04442490
org study id: 217-MDD-301B
nct id: NCT04442490
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The purpose of this study to evaluate the efficacy of SAGE-217 in the treatment of
      participants with MDD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score at Day 15
time frame: Baseline and Day 15
description: The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.
measure: Clinical Global Impression - Severity (CGI-S) Score
time frame: Day 15
description: The CGI-S is a 7-point Likert scale to rate the severity of the participant's illness at the time of assessment, relative to the clinician's past experience with participants who have the same diagnosis. A participant is assessed on severity of mental illness at the time of rating as 1=normal, not at all ill; 2=borderline ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; and 7= among the most extremely ill participants.
measure: HAM-D Total Score
time frame: Baseline and Days 3, 28, and 42
description: The 17-item HAM-D scale is used to assess the severity of depression. It is comprised of individual ratings related to the following symptoms: depressed mood, feelings of guilt, suicide, insomnia, work and activities, retardation, agitation, anxiety, somatic symptoms, genital symptoms, hypochondriasis, loss of weight, and insight. Individual items are scored on either a 3-point (0 to 2) or a 5-point scale (0 to 4), with 0=none/absent and 4=most severe. The total score is the sum of individual items, ranging from 0 to 52; where a higher score indicates more depression.
measure: Percentage of Participants With HAM-D Response
time frame: Days 15 and 42
description: The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.
measure: Percentage of Participants With HAM-D Remission
time frame: Days 15 and 42
description: HAM-D remission is defined as HAM-D total score ≤7.
measure: Percentage of Participants With Clinical Global Impression - Improvement (CGI-I) Response
time frame: Day 15
description: CGI-I response is defined as having a CGI-I score of "very much improved" or "much improved." The CGI-I employs a 7-point Likert scale to measure the overall improvement in the 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: Montgomery Åsberg Depression Rating Scale (MADRS) Total Score
time frame: Day 15
description: The MADRS is a 10-item diagnostic questionnaire used to measure the severity of depressive episodes in participants with mood disorders. Each item is rated on a 7-point scale from 0 (no symptoms) to 6 (symptoms of maximum severity). The total score ranges from 0 to 60 with a higher score indicating more depression.
measure: Hamilton Rating Scale for Anxiety (HAM-A) Total Score
time frame: Day 15
description: The 14-item HAM-A is comprised of a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A total score will be calculated as the sum of the 14 individual item scores. The scoring for HAM-A is calculated by assigning scores of 0 (not present) to 4 (very severe), with a total score range of 0 to 56.
measure: Time to First HAM-D Response
time frame: Days 1, 3, 8, 12, 15, 21, 28, 35 and 42
description: The time to response is defined as time from first administration of study drug to the time when ≥50% reduction in HAM-D score from baseline is achieved.
measure: Change From Baseline in PRO Measures of Health-Related Quality of Life, as Assessed by the 36-item Short Form version 2 (SF-36v2) Score
time frame: Baseline and Days 1, 8, 15, 28 and 42
description: Participant's health will be assessed using Patient-reported outcome (PRO) health related quality of life (HRQOL) SF-36 V2. The SF-36v2 is a 36-item measure including eight health dimensions which are four physical health status domains and four mental health status domains. Scores on each item are summed and averaged (range = 0 "worst"-100 "best"). Higher SF-36v2 scores will indicate a better state of health.
measure: Change From Baseline in PRO Measures of Depressive Symptoms, as Assessed by the 9-item Patient Health Questionnaire (PHQ-9) Score
time frame: Baseline and Days 1, 8, 15, 28 and 42
description: The PHQ-9 is a participant-rated depressive symptom severity scale where scoring is based on responses to specific questions. The score will be calculated as the sum of the 9 individual item scores. The PHQ-9 total score ranges from 1 to 27 with a higher score indicating more depression.
arm group label: SAGE-217
arm group type: Experimental
description: Participants will receive SAGE-217 capsules, once daily for 14 days. The dose may be decreased based on safety and tolerability.
arm group label: SAGE-217 Matched Placebo
arm group type: Placebo Comparator
description: Participants will receive SAGE-217 matched-placebo capsules, once daily for 14 days.
intervention type: Drug
intervention name: SAGE-217
description: SAGE-217 oral capsules.
arm group label: SAGE-217
intervention type: Drug
intervention name: Placebo
description: SAGE-217 matched-placebo oral capsules.
arm group label: SAGE-217 Matched Placebo
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
sharing ipd: No
ipd description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
submitted: August 25, 2023