<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/NCT03770780</url>
  </required_header>
  <id_info>
    <org_study_id>718-EXM-102</org_study_id>
    <nct_id>NCT03770780</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Electrophysiology, Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Response Using Magnetic Resonance Imaging of SAGE-718 Using a Ketamine Challenge in Healthy Subjects</brief_title>
  <official_title>A PHASE 1, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED CROSSOVER STUDY OF SAGE-718 USING A KETAMINE CHALLENGE, TO EVALUATE SAFETY, TOLERABILITY, PHARMACOKINETICS AND PHARMACODYNAMIC RESPONSE USING MAGNETIC RESONANCE IMAGING IN HEALTHY SUBJECTS</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 phase 1, double-blind, placebo-controlled crossover study of SAGE-718 using a&#xD;
      ketamine challenge, to evaluate the safety, tolerability, pharmacokinetics, and&#xD;
      pharmacodynamic response using magnetic resonance imaging in healthy subjects&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 12, 2018</start_date>
  <completion_date type="Actual">March 22, 2019</completion_date>
  <primary_completion_date type="Actual">March 8, 2019</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in glutamate and glutamine (GLX) in the anterior cingulate cortex (ACC), hippocampus, and pons as measured with magnetic resonance spectroscopy (MRS)</measure>
    <time_frame>Between Day 1 and Day 11</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in glutamate in the ACC, hippocampus, and pons, as measured with MRS</measure>
    <time_frame>Between Day 1 and Day 11</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by incidence of adverse events (AEs)/serious AEs (SAEs)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electroencephalograms (EEGs)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
    <description>Observed values and change from baseline in EEGs in patients post study drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electrocardiograms (ECGs)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
    <description>Observed values and change from baseline in ECGs in patients post study drug administration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Brief Psychiatric Rating Scale (BPRS)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Clinician Administered Dissociative State Scale (CADSS)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Observer's Assessment of Alertness and Sedation (OAAS)</measure>
    <time_frame>Between Baseline and Day 27</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Healthy Volunteer</condition>
  <arm_group>
    <arm_group_label>SAGE-718</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAGE-718</intervention_name>
    <description>SAGE-718 in combination with Ketamine</description>
    <arm_group_label>SAGE-718</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo in combination with Ketamine</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Subject is willing and able to provide 2 forms of identification; at least 1 must have&#xD;
             a photo.&#xD;
&#xD;
          2. Subject has a body weight ≥50 kg and body mass index ≥18.0 and ≤30.0 kg/m2 at&#xD;
             screening.&#xD;
&#xD;
          3. Subject is healthy with no history or evidence of clinically relevant medical&#xD;
             disorders as determined by the Investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subject has a history or presence of any psychiatric disease or condition including&#xD;
             suicidal ideation or behavior, has answered YES to any question on the C-SSRS at&#xD;
             screening or admission, or is currently at risk of suicide in the opinion of the&#xD;
             Investigator&#xD;
&#xD;
          2. Subject has a history or presence of a neurologic disease or condition, including but&#xD;
             not limited to epilepsy, closed head trauma with clinically significant sequelae, or a&#xD;
             prior seizure.&#xD;
&#xD;
          3. Subject has a family history of epilepsy.&#xD;
&#xD;
          4. Subject has evidence of any metal in the body that may be contraindicated for&#xD;
             receiving an MRI. This includes, but is not limited to: cardiac pacemaker, surgical&#xD;
             implants, previous accident resulting in metal or shrapnel lodged internally, tattoos&#xD;
             inked with metallic dyes, or a history of metal work without using protective eyewear.&#xD;
&#xD;
          5. Subject has claustrophobia or a history of claustrophobia.&#xD;
&#xD;
          6. Subject is unable or unwilling to remove piercings and/or jewelry that contain metal.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90806</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>November 7, 2018</study_first_submitted>
  <study_first_submitted_qc>December 7, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 10, 2018</study_first_posted>
  <last_update_submitted>January 20, 2022</last_update_submitted>
  <last_update_submitted_qc>January 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03770780
org study id: 718-EXM-102
nct id: NCT03770780
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is a phase 1, double-blind, placebo-controlled crossover study of SAGE-718 using a
      ketamine challenge, to evaluate the safety, tolerability, pharmacokinetics, and
      pharmacodynamic response using magnetic resonance imaging in healthy subjects
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in glutamate and glutamine (GLX) in the anterior cingulate cortex (ACC), hippocampus, and pons as measured with magnetic resonance spectroscopy (MRS)
time frame: Between Day 1 and Day 11
measure: Change in glutamate in the ACC, hippocampus, and pons, as measured with MRS
time frame: Between Day 1 and Day 11
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by incidence of adverse events (AEs)/serious AEs (SAEs)
time frame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electroencephalograms (EEGs)
time frame: Between Baseline and Day 27
description: Observed values and change from baseline in EEGs in patients post study drug administration
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by electrocardiograms (ECGs)
time frame: Between Baseline and Day 27
description: Observed values and change from baseline in ECGs in patients post study drug administration
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Columbia-Suicide Severity Rating Scale (C-SSRS)
time frame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Brief Psychiatric Rating Scale (BPRS)
time frame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Clinician Administered Dissociative State Scale (CADSS)
time frame: Between Baseline and Day 27
measure: Safety and tolerability of SAGE-718 alone and in combination with ketamine, as assessed by Observer's Assessment of Alertness and Sedation (OAAS)
time frame: Between Baseline and Day 27
arm group label: SAGE-718
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: SAGE-718
description: SAGE-718 in combination with Ketamine
arm group label: SAGE-718
intervention type: Drug
intervention name: Placebo
description: Placebo in combination with Ketamine
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
ipd description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.