<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/NCT03771664</url>
  </required_header>
  <id_info>
    <org_study_id>217-MDD-304</org_study_id>
    <nct_id>NCT03771664</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, and Efficacy of SAGE-217 Compared to Placebo in Adult Participants With Comorbid Major Depressive Disorder (MDD) and Insomnia</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled Study of the Safety, Tolerability, and Efficacy of SAGE-217 Compared to Placebo in Adult Subjects With Comorbid Major Depressive Disorder and Insomnia</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a randomized, double-blind, placebo-controlled study of the safety,&#xD;
      tolerability, and efficacy of SAGE-217 compared to placebo in adult participants with&#xD;
      comorbid major depressive disorder (MDD) and insomnia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    internal company decision&#xD;
  </why_stopped>
  <start_date type="Actual">February 4, 2019</start_date>
  <completion_date type="Actual">January 17, 2020</completion_date>
  <primary_completion_date type="Actual">December 20, 2019</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>Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14</measure>
    <time_frame>Baseline and Days 13, 14</time_frame>
    <description>Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)</measure>
    <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
    <description>WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Total Sleep Time (TST)</measure>
    <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
    <description>TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Latency to Persistent Sleep (LPS)</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Number of Awakenings (NAW)</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>NAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or REM sleep.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Duration of Awakenings</measure>
    <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
    <description>An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in REM Density</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in REM Activity (REMA)</measure>
    <time_frame>Baseline and Day 14 (EODBT)</time_frame>
    <description>REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Insomnia Severity Index (ISI) Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). The ISI possible total score range is from 0 to 28, categorized as follows: 0 to 7 = &quot;no clinically significant insomnia&quot;, 8 to 14 = &quot;subthreshold insomnia&quot;, 15 to 21 = &quot;clinical insomnia (moderate severity)&quot;, and 22 to 28 = &quot;clinical insomnia (severe)&quot;. Higher scores indicate severe insomnia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated 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. In this study, the CGI-S was assessed based on the severity of insomnia disorder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale</measure>
    <time_frame>Day 15</time_frame>
    <description>The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score</measure>
    <time_frame>Baseline and Day 15</time_frame>
    <description>PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. 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. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 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. Higher scores indicate severe depression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</measure>
    <time_frame>From first dose of drug up to last follow-up visit (approximately 72 days)</time_frame>
    <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Potentially Clinically Significant Vital Signs</measure>
    <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
    <description>Potentially clinically significant vital signs reported include supine and standing systolic blood pressure (SBP) [millimeters of mercury (mmHg)]: &lt;90, &gt;180, increase and decrease from baseline of &gt;=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline &gt;=20; Standing heart rate (&gt;120 beats per minute); Orthostatic SBP (&gt;=20); Orthostatic DBP (&gt;=10); Orthostatic hypotension (SBP &gt;=20 and DBP &gt;=10, SBP &gt;=20 or DBP &gt;=10).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Potentially Clinically Significant Laboratory Abnormalities</measure>
    <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
    <description>Laboratory parameters include serum chemistry- Alanine aminotransferase: &gt;3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: &gt;3x ULN; Bilirubin: &gt;1.5x ULN, &gt;2x ULN; Calcium: &lt;2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase [units per liter (U/L)]: &gt;3xULN; Potassium: &gt;5.4 mmol/L; Sodium: &gt;150 mmol/L; Hematology- Hematocrit : Male &lt;0.385 liter/liter (L/L) and Female &lt;0.345 L/L and Male &gt;0.55 L/L and Female &gt;0.49 L/L; Hemoglobin: Male &lt;115 grams/liter (g/L) and Female &lt;100 g/L; Neutrophils: &lt;1.5 10^9/L.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities</measure>
    <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
    <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for potentially clinically significant ECG abnormalities included QTcF interval (msec)- females: &gt;450 to 480, male: &gt;450 to 470, females: &gt;480 to 500, male: &gt;470 to 500 or &gt;500.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
    <description>C-SSRS scale was used to monitor suicidality. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: when response is &quot;yes&quot; for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is &quot;yes&quot; for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score</measure>
    <time_frame>Baseline, Days 18, 22, 28, 35 and 42</time_frame>
    <description>The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity [sound, smell, touch, pain], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">87</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Insomnia</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out [polysomnography (PSG)] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SAGE-217</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 milligrams (mg) capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAGE-217</intervention_name>
    <description>Administered as capsules.</description>
    <arm_group_label>SAGE-217</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Administered as capsules.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Participant had a diagnosis of MDD as diagnosed by structured clinical interview for&#xD;
             diagnostic and statistical manual of mental disorders, fifth edition, clinical trials&#xD;
             version (SCID-5-CT), with symptoms that have been present for at least a 4-week&#xD;
             period.&#xD;
&#xD;
          2. Participant had a diagnosis of Insomnia that is confirmed at screening based on the&#xD;
             diagnostic and statistical manual of mental disorders, fifth edition (DSM-5)&#xD;
             diagnostic criteria using the SCID-5-CT.&#xD;
&#xD;
          3. Participant had an Insomnia Severity Index (ISI) score greater than or equal to (&gt;=)&#xD;
             15 (moderate to severe insomnia).&#xD;
&#xD;
          4. Participant had a Montgomery-Åsberg Depression Rating Scale (MADRS) score of ≥28 prior&#xD;
             to dosing and a Hamilton Rating Scale for Depression (HAM-D) total score of ≥20.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Participant had attempted suicide associated within the current episode of MDD.&#xD;
&#xD;
          2. Participant had onset of the current depressive episode during pregnancy or 4 weeks&#xD;
             postpartum, or the participant had presented for screening during the 6-month&#xD;
             postpartum period.&#xD;
&#xD;
          3. Participant had a medical history of bipolar disorder, schizophrenia, and/or&#xD;
             schizoaffective disorder.&#xD;
&#xD;
          4. Participant had a medical history of seizures.&#xD;
&#xD;
          5. Participant had active psychosis per Investigator assessment.&#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>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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>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>Oceanside</city>
        <state>California</state>
        <zip>92056</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>Fort Myers</city>
        <state>Florida</state>
        <zip>33912</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>Miami Lakes</city>
        <state>Florida</state>
        <zip>33016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</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>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</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>Chicago</city>
        <state>Illinois</state>
        <zip>60634</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Lake Charles</city>
        <state>Louisiana</state>
        <zip>70629</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>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</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>Berlin</city>
        <state>New Jersey</state>
        <zip>08009</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>11235</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10019</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>Dayton</city>
        <state>Ohio</state>
        <zip>45417</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Salem</city>
        <state>Oregon</state>
        <zip>97301</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78754</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>December 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <results_first_submitted>August 31, 2022</results_first_submitted>
  <results_first_submitted_qc>October 13, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">October 20, 2022</results_first_posted>
  <disposition_first_submitted>October 8, 2021</disposition_first_submitted>
  <disposition_first_submitted_qc>October 13, 2022</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">October 20, 2022</disposition_first_posted>
  <last_update_submitted>October 13, 2022</last_update_submitted>
  <last_update_submitted_qc>October 13, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
    <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>
  <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 18, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03771664/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 24, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/64/NCT03771664/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled in the study at 27 investigative sites in the United States from 04 February 2019 to 17 January 2020.</recruitment_details>
      <pre_assignment_details>A total of 87 participants were randomized and 86 received drug or placebo. This study consisted of up to a 2-day single-blind placebo run-in, a 14-day double-blind treatment followed by a 7-day single-blind placebo run-out and a follow-up of up to 27 days.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out [polysomnography (PSG)] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
        <group group_id="P2">
          <title>SAGE-217</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 milligrams (mg) capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="44"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Full Analysis Set (FAS)</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety Set</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="43"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" 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="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Participant</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Randomized but not Treated</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
        <group group_id="B2">
          <title>SAGE-217</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="43"/>
            <count group_id="B2" value="43"/>
            <count group_id="B3" value="86"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42.0" spread="11.60"/>
                    <measurement group_id="B2" value="44.6" spread="12.50"/>
                    <measurement group_id="B3" value="43.3" spread="12.06"/>
                  </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="31"/>
                    <measurement group_id="B2" value="28"/>
                    <measurement group_id="B3" value="59"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="36"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="66"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="31"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African-American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14</title>
        <description>Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.</description>
        <time_frame>Baseline and Days 13, 14</time_frame>
        <population>Full analysis set (FAS) included all randomized participants who received at least 1 dose of double-blind investigational product (IP) with valid baseline and at least one post-baseline efficacy evaluation. Number analyzed signifies the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14</title>
          <description>Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.</description>
          <population>Full analysis set (FAS) included all randomized participants who received at least 1 dose of double-blind investigational product (IP) with valid baseline and at least one post-baseline efficacy evaluation. Number analyzed signifies the number of participants with data available for analyses at the specified time point.</population>
          <units>percentage of time asleep</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="43"/>
                    <count group_id="O2" value="43"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67.702" spread="14.9367"/>
                    <measurement group_id="O2" value="73.667" spread="9.8100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Average Change From Baseline at Days 13, 14</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="40"/>
                    <count group_id="O2" value="40"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.921" spread="12.1835"/>
                    <measurement group_id="O2" value="4.692" spread="8.5619"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1537</p_value>
            <p_value_desc>Average change from baseline in SE was analyzed by analysis of covariance (ANCOVA) with explanatory (treatment, baseline antidepressant use, baseline SE) and response variables [change from baseline in sleep efficiency at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>Least Square (LS) Mean Difference</param_type>
            <param_value>3.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.23</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.2</ci_lower_limit>
            <ci_upper_limit>7.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)</title>
        <description>WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.</description>
        <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)</title>
          <description>WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in WASO for Overall Duration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7.0" spread="5.87"/>
                    <measurement group_id="O2" value="-20.0" spread="5.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in WASO in Quarter 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.5" spread="1.23"/>
                    <measurement group_id="O2" value="-1.6" spread="1.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in WASO in Quarter 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.3" spread="2.33"/>
                    <measurement group_id="O2" value="-5.6" spread="2.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in WASO in Quarter 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.1" spread="2.89"/>
                    <measurement group_id="O2" value="-3.9" spread="2.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in WASO in Quarter 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="3.09"/>
                    <measurement group_id="O2" value="-11.0" spread="3.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from baseline (BL) in overall WASO</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1126</p_value>
            <p_value_desc>Change from BL in overall WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-13.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>8.07</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-29.0</ci_lower_limit>
            <ci_upper_limit>3.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in WASO in quarter 1</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9819</p_value>
            <p_value_desc>Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.63</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.3</ci_lower_limit>
            <ci_upper_limit>3.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in WASO in quarter 2</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1838</p_value>
            <p_value_desc>Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-4.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.19</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.6</ci_lower_limit>
            <ci_upper_limit>2.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in WASO in quarter 3</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0797</p_value>
            <p_value_desc>Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, baseline PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-7.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.97</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-15.0</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in WASO in quarter 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1559</p_value>
            <p_value_desc>Change from BL in WASO was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, baseline PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-6.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.24</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-14.5</ci_lower_limit>
            <ci_upper_limit>2.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Total Sleep Time (TST)</title>
        <description>TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.</description>
        <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Total Sleep Time (TST)</title>
          <description>TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in TST for Overall Duration</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.5" spread="7.73"/>
                    <measurement group_id="O2" value="28.2" spread="7.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in TST in Quarter 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.4" spread="4.00"/>
                    <measurement group_id="O2" value="7.1" spread="4.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in TST in Quarter 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.7" spread="3.02"/>
                    <measurement group_id="O2" value="8.5" spread="3.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in TST in Quarter 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.7" spread="2.93"/>
                    <measurement group_id="O2" value="3.3" spread="2.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in TST in Quarter 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.0" spread="3.10"/>
                    <measurement group_id="O2" value="11.5" spread="3.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in overall TST</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1441</p_value>
            <p_value_desc>Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>15.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.67</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.5</ci_lower_limit>
            <ci_upper_limit>37.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in TST in quarter 1</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3951</p_value>
            <p_value_desc>Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>4.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.47</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.2</ci_lower_limit>
            <ci_upper_limit>15.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in TST in quarter 2</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3705</p_value>
            <p_value_desc>Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BLPSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>3.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.16</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.5</ci_lower_limit>
            <ci_upper_limit>12.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in TST in quarter 3</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1412</p_value>
            <p_value_desc>Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>6.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.04</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>14.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in TST in quarter 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1298</p_value>
            <p_value_desc>Change from BL in TST was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>6.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.24</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>15.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Latency to Persistent Sleep (LPS)</title>
        <description>LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Latency to Persistent Sleep (LPS)</title>
          <description>LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.9" spread="5.73"/>
                    <measurement group_id="O2" value="-9.4" spread="5.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.7526</p_value>
            <p_value_desc>Change from BL in LPS was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-2.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.87</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-18.2</ci_lower_limit>
            <ci_upper_limit>13.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Number of Awakenings (NAW)</title>
        <description>NAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or REM sleep.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Number of Awakenings (NAW)</title>
          <description>NAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or REM sleep.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>awakenings</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1" spread="0.60"/>
                    <measurement group_id="O2" value="-0.2" spread="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.6769</p_value>
            <p_value_desc>Change from BL in NAW was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.83</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.0</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Duration of Awakenings</title>
        <description>An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.</description>
        <time_frame>Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Duration of Awakenings</title>
          <description>An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in Mean Duration of Awakenings in Overall</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.23"/>
                    <measurement group_id="O2" value="-3.3" spread="1.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Mean Duration of Awakenings in Quarter 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="0.80"/>
                    <measurement group_id="O2" value="-2.1" spread="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Mean Duration of Awakenings in Quarter 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.2" spread="2.21"/>
                    <measurement group_id="O2" value="-2.3" spread="2.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Mean Duration of Awakenings in Quarter 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.5" spread="2.43"/>
                    <measurement group_id="O2" value="-4.0" spread="2.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Mean Duration of Awakenings in Quarter 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.8" spread="0.49"/>
                    <measurement group_id="O2" value="-2.3" spread="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in mean duration of awakenings (MDA) in total</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0824</p_value>
            <p_value_desc>Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-3.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.70</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.4</ci_lower_limit>
            <ci_upper_limit>0.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in MDA in quarter 1</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4269</p_value>
            <p_value_desc>Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.07</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.0</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in MDA in quarter 2</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</non_inferiority_desc>
            <p_value>0.2482</p_value>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-3.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.02</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-9.5</ci_lower_limit>
            <ci_upper_limit>2.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in MDA in quarter 3</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3076</p_value>
            <p_value_desc>Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-3.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.34</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.1</ci_lower_limit>
            <ci_upper_limit>3.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in MDA in quarter 4</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4491</p_value>
            <p_value_desc>Change from BL in MDA was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-0.5</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.68</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.9</ci_lower_limit>
            <ci_upper_limit>0.8</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)</title>
        <description>The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)</title>
          <description>The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in Duration of Stage N1 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.3" spread="1.78"/>
                    <measurement group_id="O2" value="0.1" spread="1.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Duration of Stage N2 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.1" spread="5.90"/>
                    <measurement group_id="O2" value="31.7" spread="5.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Duration of Stage N3 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.4" spread="4.08"/>
                    <measurement group_id="O2" value="4.5" spread="4.09"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Duration of REM Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.7" spread="3.46"/>
                    <measurement group_id="O2" value="-9.5" spread="3.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in duration of stage (DS) N1 sleep</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8724</p_value>
            <p_value_desc>Change from BL in DS N1 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.47</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.5</ci_lower_limit>
            <ci_upper_limit>5.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in DS N2 sleep</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0238</p_value>
            <p_value_desc>Change from BL in DS N2 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>18.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>8.08</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.5</ci_lower_limit>
            <ci_upper_limit>34.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in DS N3 sleep</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3863</p_value>
            <p_value_desc>Change from BL in DS N3 sleep was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>4.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>5.62</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.3</ci_lower_limit>
            <ci_upper_limit>16.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in duration of REM sleep</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0320</p_value>
            <p_value_desc>Change from BL in REM sleep duration was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14(EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-10.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>4.69</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-19.6</ci_lower_limit>
            <ci_upper_limit>-0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration</title>
        <description>The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration</title>
          <description>The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>percentage of sleep time</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in Percentage of Stage N1 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="0.59"/>
                    <measurement group_id="O2" value="-1.0" spread="0.59"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Percentage of Stage N2 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.6" spread="1.13"/>
                    <measurement group_id="O2" value="4.3" spread="1.14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Percentage of Stage N3 Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.7" spread="1.10"/>
                    <measurement group_id="O2" value="0.5" spread="1.11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Percentage of REM Sleep</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.1" spread="0.78"/>
                    <measurement group_id="O2" value="-3.9" spread="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in percentage of stage (PS) N1 sleep time</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9524</p_value>
            <p_value_desc>Change from BL in PS N1 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score;Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>0.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.80</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.7</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in PS N2 sleep time</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0930</p_value>
            <p_value_desc>Change from BL in PS N2 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>2.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.55</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>5.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in PS N3 sleep time</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4427</p_value>
            <p_value_desc>Change from BL in PS N3 sleep time was analyzed by ANCOVA with explanatory variables: Treatment, BL antidepressant use, BL PSG-derived sleep variables score; Response variable: Change from BL in PSG-derived sleep variables at Day 14 (EODBT).</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>1.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.52</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.9</ci_lower_limit>
            <ci_upper_limit>4.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in percentage (%) of REM sleep time</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0006</p_value>
            <p_value_desc>Change from BL in % of REM sleep duration was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-3.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>1.06</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-5.9</ci_lower_limit>
            <ci_upper_limit>-1.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep</title>
        <description>Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep</title>
          <description>Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation.</population>
          <units>minutes</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in Latency to the First REM Period</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.0" spread="9.17"/>
                    <measurement group_id="O2" value="36.6" spread="9.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Latency to the Second REM Period</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="8.34"/>
                    <measurement group_id="O2" value="41.5" spread="8.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Latency to the Third REM Period</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.3" spread="8.79"/>
                    <measurement group_id="O2" value="34.9" spread="8.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in Latency to the Fourth REM Period</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.2" spread="15.42"/>
                    <measurement group_id="O2" value="45.2" spread="13.88"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in latency to the first REM period</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0083</p_value>
            <p_value_desc>Change from BL in latency to first REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>33.7</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>12.42</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>8.9</ci_lower_limit>
            <ci_upper_limit>58.4</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in latency to the second REM period</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0002</p_value>
            <p_value_desc>Change from BL in latency to second REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>43.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.95</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>21.3</ci_lower_limit>
            <ci_upper_limit>65.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in latency to the third REM period</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0009</p_value>
            <p_value_desc>Change from BL in latency to third REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>38.2</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>10.99</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>16.2</ci_lower_limit>
            <ci_upper_limit>60.2</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in latency to the fourth REM period</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0899</p_value>
            <p_value_desc>Change from BL in latency to fourth REM period was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>26.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>14.84</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.3</ci_lower_limit>
            <ci_upper_limit>56.3</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in REM Density</title>
        <description>REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in REM Density</title>
          <description>REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>number of REM per hour</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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14.2" spread="34.30"/>
                    <measurement group_id="O2" value="-185.3" spread="33.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0004</p_value>
            <p_value_desc>Change from BL in REM density was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, BL PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-171.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>46.06</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-262.9</ci_lower_limit>
            <ci_upper_limit>-79.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in REM Activity (REMA)</title>
        <description>REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.</description>
        <time_frame>Baseline and Day 14 (EODBT)</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in REM Activity (REMA)</title>
          <description>REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>number of REM</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="40"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.7" spread="50.33"/>
                    <measurement group_id="O2" value="-281.3" spread="50.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.0001</p_value>
            <p_value_desc>Change from BL in REMA was analyzed by ANCOVA with explanatory (Treatment, BL antidepressant use, baseline PSG-derived sleep variables score) and response variables [Change from BL in PSG-derived sleep variables at Day 14 (EODBT)].</p_value_desc>
            <method>ANCOVA</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-288.0</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>68.81</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-425.1</ci_lower_limit>
            <ci_upper_limit>-151.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Insomnia Severity Index (ISI) Score</title>
        <description>ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). The ISI possible total score range is from 0 to 28, categorized as follows: 0 to 7 = &quot;no clinically significant insomnia&quot;, 8 to 14 = &quot;subthreshold insomnia&quot;, 15 to 21 = &quot;clinical insomnia (moderate severity)&quot;, and 22 to 28 = &quot;clinical insomnia (severe)&quot;. Higher scores indicate severe insomnia.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Insomnia Severity Index (ISI) Score</title>
          <description>ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). The ISI possible total score range is from 0 to 28, categorized as follows: 0 to 7 = &quot;no clinically significant insomnia&quot;, 8 to 14 = &quot;subthreshold insomnia&quot;, 15 to 21 = &quot;clinical insomnia (moderate severity)&quot;, and 22 to 28 = &quot;clinical insomnia (severe)&quot;. Higher scores indicate severe insomnia.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>score 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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.1" spread="5.41"/>
                    <measurement group_id="O2" value="-6.4" spread="6.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters</title>
        <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters</title>
          <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>minutes</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="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline in sTST</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="39.9" spread="10.59"/>
                    <measurement group_id="O2" value="50.3" spread="10.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in sWASO</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.5" spread="4.72"/>
                    <measurement group_id="O2" value="-27.4" spread="4.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline in sSL</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-15.7" spread="5.26"/>
                    <measurement group_id="O2" value="-9.1" spread="5.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in sTST</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4814</p_value>
            <p_value_desc>Change from BL in sTST was analyzed by Mixed Model Repeated Measures (MMRM) with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.</p_value_desc>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>10.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>14.65</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-18.8</ci_lower_limit>
            <ci_upper_limit>39.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in sWASO</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0964</p_value>
            <p_value_desc>Change from BL in sWASO was analyzed by MMRM with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.</p_value_desc>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>-10.9</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>6.45</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-23.7</ci_lower_limit>
            <ci_upper_limit>2.0</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Change from BL in sSL</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3672</p_value>
            <p_value_desc>Change from BL in sSL was analyzed by MMRM with treatment baseline antidepressant use, baseline CSD-C value, assessment time point, and time point-by-treatment interaction as fixed effects.</p_value_desc>
            <method>MMRM</method>
            <param_type>LS Mean Difference</param_type>
            <param_value>6.6</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>7.32</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-7.9</ci_lower_limit>
            <ci_upper_limit>21.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)</title>
        <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)</title>
          <description>The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.341" spread="0.6615"/>
                    <measurement group_id="O2" value="0.521" spread="0.6175"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale</title>
        <description>The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated 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. In this study, the CGI-S was assessed based on the severity of insomnia disorder.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale</title>
          <description>The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated 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. In this study, the CGI-S was assessed based on the severity of insomnia disorder.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>score 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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.8" spread="1.07"/>
                    <measurement group_id="O2" value="-1.1" spread="1.03"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale</title>
        <description>The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.</description>
        <time_frame>Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale</title>
          <description>The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>score 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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.4" spread="0.96"/>
                    <measurement group_id="O2" value="2.9" spread="0.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score</title>
        <description>The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score</title>
          <description>The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>score 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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-6.4" spread="6.53"/>
                    <measurement group_id="O2" value="-7.9" spread="7.60"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score</title>
        <description>PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. 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. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 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. Higher scores indicate severe depression.</description>
        <time_frame>Baseline and Day 15</time_frame>
        <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score</title>
          <description>PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. 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. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 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. Higher scores indicate severe depression.</description>
          <population>FAS included all randomized participants who received at least 1 dose of double-blind IP with valid baseline and at least one post-baseline efficacy evaluation. Overall number of participants analyzed indicates the number of participants with data available for analysis for this outcome measure.</population>
          <units>score 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="39"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5.8" spread="5.69"/>
                    <measurement group_id="O2" value="-7.4" spread="6.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
        <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.</description>
        <time_frame>From first dose of drug up to last follow-up visit (approximately 72 days)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)</title>
          <description>An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Potentially Clinically Significant Vital Signs</title>
        <description>Potentially clinically significant vital signs reported include supine and standing systolic blood pressure (SBP) [millimeters of mercury (mmHg)]: &lt;90, &gt;180, increase and decrease from baseline of &gt;=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline &gt;=20; Standing heart rate (&gt;120 beats per minute); Orthostatic SBP (&gt;=20); Orthostatic DBP (&gt;=10); Orthostatic hypotension (SBP &gt;=20 and DBP &gt;=10, SBP &gt;=20 or DBP &gt;=10).</description>
        <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Potentially Clinically Significant Vital Signs</title>
          <description>Potentially clinically significant vital signs reported include supine and standing systolic blood pressure (SBP) [millimeters of mercury (mmHg)]: &lt;90, &gt;180, increase and decrease from baseline of &gt;=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline &gt;=20; Standing heart rate (&gt;120 beats per minute); Orthostatic SBP (&gt;=20); Orthostatic DBP (&gt;=10); Orthostatic hypotension (SBP &gt;=20 and DBP &gt;=10, SBP &gt;=20 or DBP &gt;=10).</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Supine SBP (mmHg): &lt;90</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP (mmHg): Decrease From Baseline of &gt;= 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine SBP (mmHg): Increase From Baseline of &gt;= 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP (mmHg): &lt;90</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP (mmHg): &gt;180</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP (mmHg): Decrease From Baseline of &gt;= 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing SBP (mmHg): Increase From Baseline of &gt;= 30</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP (mmHg): Decrease From Baseline of &gt;= 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Supine DBP (mmHg): Increase From Baseline of &gt;= 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing DBP (mmHg): Decrease From Baseline of &gt;= 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing DBP (mmHg): Increase From Baseline of &gt;= 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Standing Heart Rate (beats per minute): &gt;120</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Orthostatic SBP: &gt;= 20</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Orthostatic DBP: &gt;= 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Orthostatic Hypotension: SBP&gt;=20 and DBP&gt;=10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Orthostatic Hypotension: SBP&gt;=20 or DBP&gt;=10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Potentially Clinically Significant Laboratory Abnormalities</title>
        <description>Laboratory parameters include serum chemistry- Alanine aminotransferase: &gt;3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: &gt;3x ULN; Bilirubin: &gt;1.5x ULN, &gt;2x ULN; Calcium: &lt;2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase [units per liter (U/L)]: &gt;3xULN; Potassium: &gt;5.4 mmol/L; Sodium: &gt;150 mmol/L; Hematology- Hematocrit : Male &lt;0.385 liter/liter (L/L) and Female &lt;0.345 L/L and Male &gt;0.55 L/L and Female &gt;0.49 L/L; Hemoglobin: Male &lt;115 grams/liter (g/L) and Female &lt;100 g/L; Neutrophils: &lt;1.5 10^9/L.</description>
        <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Potentially Clinically Significant Laboratory Abnormalities</title>
          <description>Laboratory parameters include serum chemistry- Alanine aminotransferase: &gt;3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: &gt;3x ULN; Bilirubin: &gt;1.5x ULN, &gt;2x ULN; Calcium: &lt;2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase [units per liter (U/L)]: &gt;3xULN; Potassium: &gt;5.4 mmol/L; Sodium: &gt;150 mmol/L; Hematology- Hematocrit : Male &lt;0.385 liter/liter (L/L) and Female &lt;0.345 L/L and Male &gt;0.55 L/L and Female &gt;0.49 L/L; Hemoglobin: Male &lt;115 grams/liter (g/L) and Female &lt;100 g/L; Neutrophils: &lt;1.5 10^9/L.</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Alanine Aminotransferase: &gt;3x ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Alanine Aminotransferase or Aspartate Aminotransferase: &gt;3x ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: &gt;1.5x ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Bilirubin: &gt;2x ULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Calcium: &lt;2.0 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Gamma Glutamyl Transferase (U/L): &gt;3xULN</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Potassium: &gt;5.4 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Sodium: &gt;150 mmol/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematocrit: Male &lt;0.385 L/L, Female &lt;0.345 L/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hematocrit: Male &gt;0.55 L/L, Female &gt;0.49 L/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Hemoglobin: Male &lt;115 g/L, Female &lt;100 g/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Neutrophils: &lt;1.5 10^9/L</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities</title>
        <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for potentially clinically significant ECG abnormalities included QTcF interval (msec)- females: &gt;450 to 480, male: &gt;450 to 470, females: &gt;480 to 500, male: &gt;470 to 500 or &gt;500.</description>
        <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities</title>
          <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for potentially clinically significant ECG abnormalities included QTcF interval (msec)- females: &gt;450 to 480, male: &gt;450 to 470, females: &gt;480 to 500, male: &gt;470 to 500 or &gt;500.</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
        <description>C-SSRS scale was used to monitor suicidality. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: when response is &quot;yes&quot; for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is &quot;yes&quot; for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.</description>
        <time_frame>Screening up to last follow-up visit (approximately 72 days)</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
          <description>C-SSRS scale was used to monitor suicidality. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: when response is &quot;yes&quot; for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is &quot;yes&quot; for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug.</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="43"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Suicidal Ideation</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Suicidal Behavior</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score</title>
        <description>The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity [sound, smell, touch, pain], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.</description>
        <time_frame>Baseline, Days 18, 22, 28, 35 and 42</time_frame>
        <population>Safety set included all participants who received at least 1 dose of double-blind study drug. Overall number of participants analyzed signifies the number of participants with data available for analyses for this outcome measure. Number analyzed signifies the number of participants with data available for analyses at the specified time point.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
          <group group_id="O2">
            <title>SAGE-217</title>
            <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score</title>
          <description>The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity [sound, smell, touch, pain], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.</description>
          <population>Safety set included all participants who received at least 1 dose of double-blind study drug. Overall number of participants analyzed signifies the number of participants with data available for analyses for this outcome measure. Number analyzed signifies the number of participants with data available for analyses at the specified time point.</population>
          <units>score 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="40"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Change From Baseline at Day 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="4.70"/>
                    <measurement group_id="O2" value="-1.0" spread="5.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline at Day 22</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="38"/>
                    <count group_id="O2" value="41"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.9" spread="5.08"/>
                    <measurement group_id="O2" value="-2.5" spread="4.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline at Day 28</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="39"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.2" spread="5.56"/>
                    <measurement group_id="O2" value="-0.1" spread="6.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline at Day 35</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.6" spread="6.47"/>
                    <measurement group_id="O2" value="0.1" spread="5.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Change From Baseline at Day 42</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="39"/>
                    <count group_id="O2" value="37"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.6" spread="6.58"/>
                    <measurement group_id="O2" value="-0.8" spread="5.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of drug up to last follow-up visit (approximately 72 days)</time_frame>
      <desc>Safety set included all participants who received at least 1 dose of double-blind study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
        <group group_id="E2">
          <title>SAGE-217</title>
          <description>Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 mg capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 21.1</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="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Focal dyscognitive seizures</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="18" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="17" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="43"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="43"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="43"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="43"/>
              </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 PI can either be a party and subject to the same restrictions as the institution, or if not a party, the restrictions are described on the face of the contract (i.e., PI is a contractor of the institution; PI is part of a larger group of study personnel; institution has contracted with or otherwise bound all study personnel under confidentiality obligations and requirements to vest intellectual property to the institution).</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated early due to sponsor's decision and there were no safety concerns.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Monitor</name_or_title>
      <organization>Sage Therapeutics</organization>
      <phone>(617) 299-8380</phone>
      <email>info@sagerx.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/NCT03771664
org study id: 217-MDD-304
nct id: NCT03771664
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is a randomized, double-blind, placebo-controlled study of the safety,
      tolerability, and efficacy of SAGE-217 compared to placebo in adult participants with
      comorbid major depressive disorder (MDD) and insomnia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Average Change From Baseline in Sleep Efficiency (SE) as Assessed by Polysomnogram (PSG) at Days 13 and 14
time frame: Baseline and Days 13, 14
description: Sleep Efficiency (SE) is the percentage of time in bed spent asleep, determined during an 8-hour overnight PSG recording. The PSG measures the physiological process of sleep by monitoring body functions including brain waves, eye movements, muscle activity or skeletal muscle activation, heart rhythm, blood oxygen saturation, and breathing functions. Stages of sleep include rapid eye movement (REM), non-rapid eye movement (NREM), NREM stage 1 (N1), NREM stage 2 (N2), and NREM stage 3 (N3), scored through evaluation of the electroencephalogram (EEG) signal. The average of 2 nights' PSG measurements at Days 13 and 14 is reported in this outcome measure.
measure: Change From Baseline in Wake After Sleep Onset (WASO) From Persistent Sleep Onset to Lights-on (Final Wake Time)
time frame: Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording
description: WASO is the total wake time (in minutes) calculated from persistent sleep onset to lights-on (final wake time). In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) WASO and in each quarter (for the each 2-hour duration) WASO of the 8-hour PSG recording is reported.
measure: Change From Baseline in Total Sleep Time (TST)
time frame: Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording
description: TST is the duration of total sleep time (NREM + REM) (in minutes) from lights off to lights on during PSG recording. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) TST and in each quarter (for the each 2-hour duration) TST of the 8-hour PSG recording is reported.
measure: Change From Baseline in Latency to Persistent Sleep (LPS)
time frame: Baseline and Day 14 (EODBT)
description: LPS is duration in minutes from lights off to the first epoch of 20 consecutive non-wake epochs.
measure: Change From Baseline in Number of Awakenings (NAW)
time frame: Baseline and Day 14 (EODBT)
description: NAW was calculated from the onset of persistent sleep until lights on. An awakening is defined as at least 2 consecutive epochs of wake. Individual awakenings were separated by at least 1 epoch of Stage N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) or REM sleep.
measure: Change From Baseline in Mean Duration of Awakenings
time frame: Baseline, Day 14: Overall duration (8 hours) and each 2-hour quarter duration (quarter 1: 0 to 2 hours, quarter 2: 2 to 4 hours, quarter 3: 4 to 6 hours, quarter 4: 6 to 8 hours) of PSG recording
description: An awakening is defined as at least 2 consecutive epochs of wake. Mean duration of awakenings is an arithmetic mean calculated as the sum of duration of all awakenings (in minutes) divided by the number of awakenings. In this outcome measure, change from baseline at Day 14 in overall (for the whole 8-hour period) mean duration of awakenings and in each quarter (for the each 2-hour duration) mean duration of awakenings is reported.
measure: Change From Baseline in Duration of Stage N1, N2, N3, and REM Sleep (in Minutes)
time frame: Baseline and Day 14 (EODBT)
description: The change in duration (minutes) of NREM sleep stages: N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep time from lights off to lights on during PSG recording was reported.
measure: Change From Baseline in Percentage of N1, N2, N3 Stages, and REM Sleep Duration
time frame: Baseline and Day 14 (EODBT)
description: The change from baseline in duration of sleep time (percentage) of NREM sleep stages N1 (light sleep), N2 (also fairly light, with sudden increases in brain wave frequency known as sleep spindles), N3 (slow wave or deep sleep) and REM sleep was reported. Duration of sleep time was calculated from lights off to lights on during PSG recording.
measure: Change From Baseline in Latency to the First Period and Each Subsequent Period (Periods 2, 3, 4) of REM Sleep
time frame: Baseline and Day 14 (EODBT)
description: Latency to REM sleep (REML) for first period is the number of non-REM epochs in terms of minutes (stages N1 [light sleep], N2 [also fairly light, with sudden increases in brain wave frequency known as sleep spindles], N3 [slow wave or deep sleep]) from LPS to the first epoch of REM sleep. REML for second and subsequent REM periods is the number of non-REM and REM epochs in terms of minutes (stages N1, N2, N3, and REM) from LPS to the first epoch of the 2nd REM period, or subsequent REM period.
measure: Change From Baseline in REM Density
time frame: Baseline and Day 14 (EODBT)
description: REM density is the total number of REMs divided by the total duration of REM sleep in hours during time in bed (TIB).
measure: Change From Baseline in REM Activity (REMA)
time frame: Baseline and Day 14 (EODBT)
description: REMA is the total number of REMs during REM sleep, observed on the electrooculographic (EOG) channels of the PSG. The rapid eye movements must be at least 25 microvolts (uV) in amplitude.
measure: Change From Baseline in Insomnia Severity Index (ISI) Score
time frame: Baseline and Day 15
description: ISI is a validated questionnaire designed to assess the nature, severity, and impact of insomnia. The ISI uses a 5-point Likert scale to measure various aspects of insomnia severity (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe), satisfaction with current sleep pattern (0 = very satisfied, 1 = satisfied, 2 = neutral, 3 = dissatisfied, 4 = very dissatisfied), and various aspects of the impact of insomnia on daily functioning (0 = not at all, 1 = a little, 2 = somewhat, 3 = much, 4 = very much). The ISI possible total score range is from 0 to 28, categorized as follows: 0 to 7 = "no clinically significant insomnia", 8 to 14 = "subthreshold insomnia", 15 to 21 = "clinical insomnia (moderate severity)", and 22 to 28 = "clinical insomnia (severe)". Higher scores indicate severe insomnia.
measure: Change From Baseline in Consensus Sleep Diary - Core (CSD-C) Parameters
time frame: Baseline and Day 15
description: The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including subjective sleep latency (sSL), subjective TST (sTST), subjective WASO (sWASO), and subjective sleep quality (sSQ), were derived from the CSD-C responses. Change from baseline in sSL, sTST and sWASO was reported in this outcome measure.
measure: Change From Baseline in CSD-C Parameter: Subjective Sleep Quality (sSQ)
time frame: Baseline and Day 15
description: The CSD-C collects subjective responses to a series of questions related to participant's daily sleep pattern (i.e., time to bed, time to fall asleep, time to final awakening, and a question related to quality of sleep). Sleep parameters including sSL, sTST, sWASO, and sSQ, were derived from the CSD-C responses. Change from baseline in sSQ was reported in this outcome measure. Sleep quality is rated on a 5-point Likert scale ranging from 1 (very poor) to 5 (very good). Higher ratings indicate better sleep quality.
measure: Change From Baseline in Clinical Global Impression - Severity (CGI-S) Scale
time frame: Baseline and Day 15
description: The severity of illness for each participant was rated using the CGI-S on a 7-point Likert scale with a total score range of 1-7 where a higher score represented a worse outcome. The participants were rated 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. In this study, the CGI-S was assessed based on the severity of insomnia disorder.
measure: Mean Score of the Clinical Global Impression - Improvement (CGI-I) Scale
time frame: Day 15
description: The overall improvement in the participant's condition was assessed using CGI-I on a 7-point Likert scale with a total score range of 0-7 where a higher score represented a worse outcome. The participants were rated as: 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. In this study, the CGI-I was assessed based on the improvement of insomnia disorder.
measure: Change From Baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D) Total Score
time frame: Baseline and Day 15
description: The 17-item HAM-D was used to rate the severity of depression in participants who were already diagnosed as depressed. The 17-item HAM-D comprises individual ratings related to the following symptoms: Depressed mood (sadness, hopeless, helpless, worthless), feelings of guilt, suicide, insomnia (early, middle, late), work and activities, retardation (slowness of thought and speech; Impaired ability to concentrate; Decreased motor activity), agitation, anxiety (psychic and somatic), somatic symptoms (gastrointestinal and general), genital symptoms, hypochondriasis, loss of weight, and insight. The HAM-D total score was calculated as the sum of the 17 individual item scores and could range from 0 to 52. Higher scores indicate severe depression.
measure: Change From Baseline in the 9-item Patient Health Questionnaire (PHQ-9) Score
time frame: Baseline and Day 15
description: PHQ-9 is a participant-rated depressive symptom severity scale to monitor severity over time for newly diagnosed participants or participants in current treatment for depression. 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. The PHQ-9 total score was calculated as the sum of the 9 individual item scores. The PHQ-9 total score was categorized as follows: 1 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. Higher scores indicate severe depression.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
time frame: From first dose of drug up to last follow-up visit (approximately 72 days)
description: An adverse event (AE) is any untoward medical occurrence in a clinical trial participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE is an AE that occurs after the first administration of double-blind study drug or placebo. SAE is any untoward medical occurrence that at any dose results in death, is immediately life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, results in a congenital abnormality or birth defect.
measure: Number of Participants With Potentially Clinically Significant Vital Signs
time frame: Screening up to last follow-up visit (approximately 72 days)
description: Potentially clinically significant vital signs reported include supine and standing systolic blood pressure (SBP) [millimeters of mercury (mmHg)]: <90, >180, increase and decrease from baseline of >=30; Supine and standing diastolic blood pressure (DBP) (mmHg): Increase and decrease from baseline >=20; Standing heart rate (>120 beats per minute); Orthostatic SBP (>=20); Orthostatic DBP (>=10); Orthostatic hypotension (SBP >=20 and DBP >=10, SBP >=20 or DBP >=10).
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities
time frame: Screening up to last follow-up visit (approximately 72 days)
description: Laboratory parameters include serum chemistry- Alanine aminotransferase: >3x upper limit of normal (ULN); Alanine aminotransferase or aspartate aminotransferase: >3x ULN; Bilirubin: >1.5x ULN, >2x ULN; Calcium: <2.0 millimoles per liter (mmol/L); Gamma Glutamyl Transferase [units per liter (U/L)]: >3xULN; Potassium: >5.4 mmol/L; Sodium: >150 mmol/L; Hematology- Hematocrit : Male <0.385 liter/liter (L/L) and Female <0.345 L/L and Male >0.55 L/L and Female >0.49 L/L; Hemoglobin: Male <115 grams/liter (g/L) and Female <100 g/L; Neutrophils: <1.5 10^9/L.
measure: Number of Participants With Potentially Clinically Significant Electrocardiogram (ECG) Abnormalities
time frame: Screening up to last follow-up visit (approximately 72 days)
description: Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR, QRS, QT, and QTcF) as well as any rhythm abnormalities were recorded. Criteria for potentially clinically significant ECG abnormalities included QTcF interval (msec)- females: >450 to 480, male: >450 to 470, females: >480 to 500, male: >470 to 500 or >500.
measure: Number of Participants With Suicidal Ideation and Suicidal Behavior Using the Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Screening up to last follow-up visit (approximately 72 days)
description: C-SSRS scale was used to monitor suicidality. The C-SSRS includes 'yes' or 'no' responses for 5 questions for assessment of suicidal ideation and behavior. Any suicidal behavior: when response is "yes" for any these questions- actual attempt to suicide, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt, preparatory acts. Any suicidal ideation: when response is "yes" for any of these questions- wish to be dead, non-specific active suicidal thoughts, active suicidal ideation with methods without intent to act or some intent to act, without specific plan or with specific plan and intent to suicide.
measure: Change From Baseline in the Withdrawal Symptoms as Measured by the Physician Withdrawal Checklist (PWC-20) Total Score
time frame: Baseline, Days 18, 22, 28, 35 and 42
description: The PWC-20 was used to monitor for the presence of potential withdrawal symptoms following discontinuation of IP. It consists of a list of 20 symptoms (loss of appetite, nausea-vomiting, diarrhea, anxiety-nervousness, irritability, dysphoric mood-depression, insomnia, fatigue-lethargy-lack of energy, poor coordination, restlessness-agitation, diaphoresis, tremor-tremulousness, dizziness-lightheadedness, headaches, muscle aches or stiffness, weakness, increased acuity [sound, smell, touch, pain], paresthesia, difficulty concentrating and remembering, depersonalization-derealization) that were rated by the investigator on a scale of 0 (not present) to 3 (severe). The total score was derived as the sum of individual item scores, which ranges from 0 to 60. Higher scores indicate severe withdrawal. The total scores of PWC-20 were reported in this outcome measure.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217 matching placebo capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217 matching placebo capsules, orally, once daily, 30 minutes prior to lights out [polysomnography (PSG)] on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
arm group label: SAGE-217
arm group type: Experimental
description: Participants received SAGE-217 matching placebo capsules (single-blind), orally, once daily prior to Day 1 (Days -2 and -1) followed by self-administration of SAGE-217, 30 milligrams (mg) capsules, orally, once daily for 12 days. Thereafter participants received SAGE-217, 30 mg capsules, orally, once daily, 30 minutes prior to lights out (PSG) on Days 13 and 14 (double-blind). Thereafter participants self-administered SAGE-217 matching placebo capsules (single-blind), orally, once daily on Days 15 to 21.
intervention type: Drug
intervention name: SAGE-217
description: Administered as capsules.
arm group label: SAGE-217
intervention type: Drug
intervention name: Placebo
description: Administered as capsules.
arm group label: 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: Sleep Initiation and Maintenance Disorders
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.
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limitations and caveats: The study was terminated early due to sponsor's decision and there were no safety concerns.
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