<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/NCT04476017</url>
  </required_header>
  <id_info>
    <org_study_id>718-CNP-201</org_study_id>
    <nct_id>NCT04476017</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety and Tolerability of SAGE-718 in Participants With Parkinson's Disease Mild Cognitive Impairment (PD-MCI)</brief_title>
  <official_title>An Open-Label Evaluation of the Safety and Tolerability of SAGE-718 in Participants With Parkinson's Disease Mild Cognitive Impairment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sage Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sage Therapeutics</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary purpose of this two-part study was to evaluate the safety and tolerability of&#xD;
      SAGE-718 and its effects on cognitive, neuropsychiatric, and motor symptoms in participants&#xD;
      with Parkinson's disease mild cognitive impairment (PD-MCI).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2020</start_date>
  <completion_date type="Actual">March 25, 2022</completion_date>
  <primary_completion_date type="Actual">March 25, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>The study had two parts: Part A and Part B with unique participants for each study part. Part B was started after Part A was completed.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</measure>
    <time_frame>From first dose of study drug up to 28 days</time_frame>
    <description>An adverse event (AE) was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</measure>
    <time_frame>From first dose of study drug up to 42 days</time_frame>
    <description>An AE was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements</measure>
    <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
    <description>Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments</measure>
    <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
    <description>Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements</measure>
    <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
    <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia [QTcF]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
    <description>The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included &quot;yes&quot; or &quot;no&quot;' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Cognitive Dysfunction</condition>
  <arm_group>
    <arm_group_label>Part A: SAGE-718 3 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SAGE-718 3 milligrams (mg) tablets, once daily with food in the morning for 14 days.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: SAGE-718 3 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SAGE-718</intervention_name>
    <description>Oral tablets.</description>
    <arm_group_label>Part A: SAGE-718 3 mg</arm_group_label>
    <arm_group_label>Part B: SAGE-718 3 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Meet the following criteria for PD-MCI: Have a confirmed diagnosis of idiopathic PD&#xD;
             according to 2015 Movement Disorder Society (MDS) clinical diagnostic criteria; Meet&#xD;
             MDS Task Force Criteria for MCI in PD.&#xD;
&#xD;
          2. Have a score of 20 to 25 (inclusive) on the Montreal Cognitive Assessment (MoCA) at&#xD;
             Screening.&#xD;
&#xD;
          3. Meet criteria for Hoehn &amp; Yahr Stage I to III (mild to moderate motor severity) at&#xD;
             Screening.&#xD;
&#xD;
          4. Have stable motor symptoms for at least 4 weeks prior to screening, in the opinion of&#xD;
             the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Have a diagnosis of dementia of any etiology, including but not limited to: Dementia&#xD;
             associated with PD (probable or possible), Dementia with Lewy Bodies, Alzheimer's&#xD;
             Dementia, and Vascular Dementia.&#xD;
&#xD;
          2. Have any indication of parkinsonism other than idiopathic PD.&#xD;
&#xD;
          3. In the opinion of the investigator, be experiencing unpredictable fluctuations in&#xD;
             motor and/or nonmotor symptoms associated with PD.&#xD;
&#xD;
          4. Have an ongoing central nervous system condition other than idiopathic PD, including&#xD;
             active neurologic and/or nonremitted psychiatric disorders, in the opinion of the&#xD;
             investigator.&#xD;
&#xD;
          5. Have a history of brain surgery, deep brain stimulation, a significant head injury&#xD;
             causing loss of consciousness greater than 30 minutes, or hospitalization due to a&#xD;
             brain injury.&#xD;
&#xD;
          6. Have experienced significant psychotic symptoms within the past 3 months, including&#xD;
             those associated with PD medications, as determined by the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</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>Port Charlotte</city>
        <state>Florida</state>
        <zip>33980</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>West Palm Beach</city>
        <state>Florida</state>
        <zip>33407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sage Investigational Site</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 15, 2020</study_first_submitted>
  <study_first_submitted_qc>July 15, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 17, 2020</study_first_posted>
  <results_first_submitted>May 9, 2023</results_first_submitted>
  <results_first_submitted_qc>May 9, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">June 6, 2023</results_first_posted>
  <last_update_submitted>July 20, 2023</last_update_submitted>
  <last_update_submitted_qc>July 20, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease</keyword>
  <keyword>Cognitive Dysfunction</keyword>
  <keyword>SAGE-718</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</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>April 29, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT04476017/Prot_002.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>May 6, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT04476017/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were enrolled in the study at 4 investigative sites in the United States and took part in the study that ran from 31 July 2020 to 25 March 2022.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Part A: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 milligrams (mg) tablets, once daily with food in the morning for 14 days in Part A of study.</description>
        </group>
        <group group_id="P2">
          <title>Part B: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Part A (28 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="11"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Part B (42 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety Set included all participants who were administered investigational product (IP).</population>
      <group_list>
        <group group_id="B1">
          <title>Part A: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
        </group>
        <group group_id="B2">
          <title>Part B: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</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="11"/>
            <count group_id="B2" value="7"/>
            <count group_id="B3" value="18"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="69.1" lower_limit="51" upper_limit="74"/>
                    <measurement group_id="B2" value="70.3" lower_limit="63" upper_limit="75"/>
                    <measurement group_id="B3" value="69.6" lower_limit="51" upper_limit="75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="18"/>
                  </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 (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</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>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_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_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
        <description>An adverse event (AE) was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
        <time_frame>From first dose of study drug up to 28 days</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
          <description>An adverse event (AE) was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
        <description>An AE was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
        <time_frame>From first dose of study drug up to 42 days</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part B: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)</title>
          <description>An AE was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements</title>
        <description>Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.</description>
        <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
          </group>
          <group group_id="O2">
            <title>Part B: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements</title>
          <description>Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="7"/>
              </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>Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments</title>
        <description>Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.</description>
        <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
          </group>
          <group group_id="O2">
            <title>Part B: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments</title>
          <description>Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="7"/>
              </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>Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements</title>
        <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia [QTcF]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.</description>
        <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
          </group>
          <group group_id="O2">
            <title>Part B: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements</title>
          <description>Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia [QTcF]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="7"/>
              </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>Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
        <description>The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included &quot;yes&quot; or &quot;no&quot;' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.</description>
        <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
        <population>Safety Set included all participants who were administered IP.</population>
        <group_list>
          <group group_id="O1">
            <title>Part A: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
          </group>
          <group group_id="O2">
            <title>Part B: SAGE-718 3 mg</title>
            <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
          </group>
        </group_list>
        <measure>
          <title>Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
          <description>The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included &quot;yes&quot; or &quot;no&quot;' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.</description>
          <population>Safety Set included all participants who were administered IP.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Suicidal Ideation</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>
              <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_list>

    <reported_events>
      <time_frame>From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B</time_frame>
      <desc>Safety Set included all participants who were administered IP.</desc>
      <group_list>
        <group group_id="E1">
          <title>Part A: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 14 days in Part A of study.</description>
        </group>
        <group group_id="E2">
          <title>Part B: SAGE-718 3 mg</title>
          <description>Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days in Part B of study.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (23.0)</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="5" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Large intestine polyp</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Abdominal discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Eye contusions</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Activated partial thromboplastin time prolonged</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>International normalized ratio increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Parkinsonism</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocyturia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="11"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="7"/>
              </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>
    <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/NCT04476017
org study id: 718-CNP-201
nct id: NCT04476017
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
The primary purpose of this two-part study was to evaluate the safety and tolerability of
      SAGE-718 and its effects on cognitive, neuropsychiatric, and motor symptoms in participants
      with Parkinson's disease mild cognitive impairment (PD-MCI).
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: The study had two parts: Part A and Part B with unique participants for each study part. Part B was started after Part A was completed.
primary purpose: Treatment
masking: None (Open Label)
measure: Part A: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
time frame: From first dose of study drug up to 28 days
description: An adverse event (AE) was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
measure: Part B: Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE)
time frame: From first dose of study drug up to 42 days
description: An AE was any untoward medical occurrence in a participant administered with 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, symptom, or disease temporally associated with the use of an IP whether or not related to the product. An AE can include any undesirable medical condition, even if no study treatment has been administered. TEAEs were defined as an AE with an onset date on or after the date of the first dose of IP or any worsening of a pre-existing medical condition/AE with onset after the start of IP and throughout the study. Percentages are rounded off to the nearest single decimal.
measure: Part A and B: Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements
time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
description: Vital signs included temperature, respiratory rate, heart rate (supine and standing), systolic blood pressure (supine and standing) and diastolic blood pressure (supine and standing). Percentage of participants with clinically significant change in vital signs measurements which were deemed clinically significant by the investigator were reported.
measure: Part A and B: Percentage of Participants With Clinically Significant Changes in Laboratory Assessments
time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
description: Laboratory tests assessments included hematology, biochemistry, coagulation and urinalysis. Percentage of participants with clinically significant change in laboratory assessments which were deemed clinically significant by the investigator were reported.
measure: Part A and B: Percentage of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Measurements
time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
description: Supine 12-lead ECGs were performed in triplicate and the standard intervals (heart rate, PR interval, QRS duration, QT interval, and corrected QT interval by Fridericia [QTcF]). Percentage of participants with clinically significant change in ECG measurements which were deemed clinically significant by the investigator were reported.
measure: Part A and B: Percentage of Participants With a Response of 'Yes' to Any Suicidal Ideation or Suicidal Behaviors Item Assessed Using the Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: From first dose of study drug up to 28 days for Part A, and up to 42 days for Part B
description: The C-SSRS scale consisted of a baseline evaluation (at screening) that assessed the lifetime experience of participants with suicidal ideation (SI) and suicidal behavior (SB) and a postbaseline evaluation that focused on suicidality since the last study visit. The C-SSRS included "yes" or "no"' responses for assessment of suicidal ideation and behavior as well as numeric ratings for the severity of ideation, if present (from 1 to 5, with 5 being the most severe). The C-SSRS SI items involved wish to be dead, non-specific active suicidal thoughts, active SI with any methods, active SI with some intent and active SI with a specific plan. The C-SSRS SB items involved preparatory acts or behavior, aborted attempt, interrupted attempt, actual attempt (non-fatal) and completed suicide. Percentage of participants with a response of 'yes' are reported for both suicidal ideation and behavior in this OM.
arm group label: Part A: SAGE-718 3 mg
arm group type: Experimental
description: Participants received SAGE-718 3 milligrams (mg) tablets, once daily with food in the morning for 14 days.
arm group label: Part B: SAGE-718 3 mg
arm group type: Experimental
description: Participants received SAGE-718 3 mg tablets, once daily with food in the morning for 28 days.
intervention type: Drug
intervention name: SAGE-718
description: Oral tablets.
arm group label: Part A: SAGE-718 3 mg
arm group label: Part B: SAGE-718 3 mg
criteria: 
gender: All
minimum age: 50 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Cognitive Dysfunction
sharing ipd: No
ipd description: Data sharing will be consistent with the results submission policy of ClinicalTrials.gov.
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 