<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/NCT03017508</url>
  </required_header>
  <id_info>
    <org_study_id>1605017768</org_study_id>
    <nct_id>NCT03017508</nct_id>
  </id_info>
  <brief_title>Acute Anxiolytic Effects of Riluzole on Subjects With Social Anxiety Disorder</brief_title>
  <official_title>Double-Blind, Placebo-Controlled, Single-Dose Crossover Study Examining the Effects of Sublingual Riluzole (BHV-0223) on Public Speaking in Social Anxiety Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Yale University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Biohaven Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Yale University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The goal of the current proposal is to examine if sublingual riluzole can reduce anxiety in&#xD;
      people with social anxiety disorder during a public speaking task.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigators propose conducting a double-blind, placebo controlled crossover study&#xD;
      examining the effects of BHV-0223 on public speaking anxiety. Twenty participants with DSM-5&#xD;
      defined social anxiety disorder and clinically significant public speaking anxiety on the&#xD;
      Impromptu Speech Task will be enrolled in a challenge study. Participants will be given&#xD;
      BHV-0223 (or placebo) under double-blind crossover conditions 1 hour prior to performing each&#xD;
      of 2 impromptu speech tasks. The two study days involving BHV-0223 (or placebo)&#xD;
      administration and impromptu speech task will be separated by 2 to 10 days to allow for&#xD;
      medication washout. There will be a final follow-up visit 2 to 10 days later to perform a&#xD;
      complete Physical exam and do follow-up liver function testing and a Complete Blood Count.&#xD;
      Our primary outcome will examine BHV-0223's effects (compared to placebo) on self-rated&#xD;
      anxiety during the impromptu speech task. The investigators will also collect physiological&#xD;
      measures of anxiety, clinician-rated measures of anxiety, and measures of speech performance&#xD;
      as secondary outcomes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2017</start_date>
  <completion_date type="Actual">January 29, 2021</completion_date>
  <primary_completion_date type="Actual">December 2019</primary_completion_date>
  <phase>Phase 2/Phase 3</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>Other</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>VAS-anxiety Immediately After the Impromptu Speech Task</measure>
    <time_frame>up to 60 minutes</time_frame>
    <description>Measure Description: In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents &quot;no anxiety&quot; and the right end (100mm) represents &quot;the worst anxiety ever felt&quot; by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">22</enrollment>
  <condition>Social Anxiety Disorder</condition>
  <condition>Performance Anxiety</condition>
  <arm_group>
    <arm_group_label>BHV-0223 (Sublingual Riluzole)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be given one dose of BHV-0223 (sublingual riluzole) 35mg before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be given one dose of an identical looking sublingual placebo before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BHV-0223</intervention_name>
    <description>35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for 3 hours.</description>
    <arm_group_label>BHV-0223 (Sublingual Riluzole)</arm_group_label>
    <other_name>sublingual riluzole</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for three hours.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female (post-menopausal, surgically sterile, or negative pregnancy test at&#xD;
             screening and agreement to utilize an established birth control, including complete&#xD;
             abstinence, during the testing period) between the age of 18 and 65 yrs.&#xD;
&#xD;
          2. Meet DSM-5 criteria for social anxiety disorder by structured clinical interview&#xD;
             (SCID) and have a LSAS public speaking subscale score &gt;6.&#xD;
&#xD;
          3. Stable psychiatric medications. Participants must have had stable doses of all&#xD;
             psychiatric medications for the month prior to treatment and have been on stable doses&#xD;
             of SSRI and antidepressants for at least 1 month prior to study enrollment. As needed&#xD;
             benzodiazepine use will be permitted as long as subjects refrain from using&#xD;
             benzodiazepines for the 48 hours prior to the study.&#xD;
&#xD;
          4. Medically and neurologically healthy on the basis of physical examination, SMAC-20&#xD;
             (including LFT's, TFT's), VDRL, CBC w/ diff, urinalysis, urine toxicology, EKG, and&#xD;
             medical history. Individuals with stable medical problems that do not have CNS effects&#xD;
             or interfere with medications administered (e.g., oral hypoglycemics) may be included&#xD;
             if their medications have not been adjusted in the month prior to entry;&#xD;
&#xD;
          5. Urine toxicology screen negative for drug of abuse.&#xD;
&#xD;
          6. Able to provide written informed consent according to the Yale Human Investigation&#xD;
             Committee (HIC) guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Positive pregnancy test&#xD;
&#xD;
          2. Breastfeeding females&#xD;
&#xD;
          3. History of substance abuse disorder (ETOH, cocaine, opiates, PCP) within the last 6&#xD;
             months or positive urine toxicology on screening (within the previous 6 months).&#xD;
&#xD;
          4. History of pervasive developmental disorder or psychotic disorder by DSM-IV-TR&#xD;
             criteria.&#xD;
&#xD;
          5. Presence of dentures, braces, piercings at the time of dosing, or any physical&#xD;
             findings in the mouth or tongue that, in the opinion of the Principal Investigator,&#xD;
             would be likely to interfere with successful completion of the dosing procedure.&#xD;
&#xD;
          6. Participants with a medical condition that might interfere with the physiological&#xD;
             absorption and motility (ie, gastric bypass, duodenectomy) or gastric bands.&#xD;
&#xD;
          7. Participants with any clinically significant abnormality or abnormal laboratory test&#xD;
             results.&#xD;
&#xD;
          8. Participant has a current diagnosis of viral hepatitis (HBsAG or HVC) or a history of&#xD;
             liver disease.&#xD;
&#xD;
          9. Participant has significant history of seizure disorder other than a single childhood&#xD;
             febrile seizure (eg. Epilepsy)&#xD;
&#xD;
         10. Participant using any drugs known to induce or inhibit CYP 1A2 metabolism (examples of&#xD;
             inducers: rifampin, carbamazepine, etc.; examples of inhibitors: fluvoxamine,&#xD;
             ciprofloxacin, fluoroquinolones, etc.) within 30 days prior to the first study drug&#xD;
             administration.&#xD;
&#xD;
         11. Participants with a history of allergic reactions to riluzole or other related drugs.&#xD;
&#xD;
         12. Participant has a history of anaphylaxis, a documented hypersensitivity reaction, or a&#xD;
             clinically important reaction to any drug.&#xD;
&#xD;
         13. Participant has received another investigational drug or device within the 30 days (90&#xD;
             days for biologics) prior to the first dosing or is currently participating in an&#xD;
             investigational study involving no drug administration.&#xD;
&#xD;
         14. Participant with clinically significant electrocardiogram (ECG) abnormalities (QTcF&#xD;
             &gt;450 msec) or vital sign abnormalities (systolic blood pressure lower than 90 or over&#xD;
             140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or heart rate less&#xD;
             than 50 or over 100 bpm) at Screening or Baseline (Day -1).&#xD;
&#xD;
         15. Any reason which, in the opinion of the Principal Investigator, would prevent the&#xD;
             participant from being in the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michael H. Bloch, MD, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Connecticut Mental Health Center</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06508</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Davidson JR. Use of benzodiazepines in social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. J Clin Psychiatry. 2004;65 Suppl 5:29-33.</citation>
    <PMID>15078116</PMID>
  </reference>
  <reference>
    <citation>Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM. Open-label trial of riluzole in generalized anxiety disorder. Am J Psychiatry. 2005 Dec;162(12):2379-81. doi: 10.1176/appi.ajp.162.12.2379.</citation>
    <PMID>16330605</PMID>
  </reference>
  <reference>
    <citation>Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs. 2008;22(9):761-86. doi: 10.2165/00023210-200822090-00004.</citation>
    <PMID>18698875</PMID>
  </reference>
  <reference>
    <citation>Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007 Mar 15;61(6):822-5. doi: 10.1016/j.biopsych.2006.08.037. Epub 2006 Dec 4.</citation>
    <PMID>17141740</PMID>
  </reference>
  <reference>
    <citation>Baker SL, Heinrichs N, Kim HJ, Hofmann SG. The liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis. Behav Res Ther. 2002 Jun;40(6):701-15. doi: 10.1016/s0005-7967(01)00060-2.</citation>
    <PMID>12051488</PMID>
  </reference>
  <reference>
    <citation>Ries BJ, McNeil DW, Boone ML, Turk CL, Carter LE, Heimberg RG. Assessment of contemporary social phobia verbal report instruments. Behav Res Ther. 1998 Oct;36(10):983-94. doi: 10.1016/s0005-7967(98)00078-3.</citation>
    <PMID>9714948</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>January 9, 2017</study_first_submitted>
  <study_first_submitted_qc>January 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 11, 2017</study_first_posted>
  <results_first_submitted>March 9, 2021</results_first_submitted>
  <results_first_submitted_qc>April 30, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">May 20, 2021</results_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 20, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cross-over study</keyword>
  <keyword>Riluzole</keyword>
  <keyword>Double-blind study</keyword>
  <keyword>Speech task</keyword>
  <keyword>Social Anxiety Disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety Disorders</mesh_term>
    <mesh_term>Phobia, Social</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Riluzole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 28, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/08/NCT03017508/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>28 participants were screened in person at the Yale Child Study Center. Of these, 22 were enrolled and 6 were excluded (2 did not have a diagnosis of Public Speaking Anxiety, 3 had a positive utox and 1 had uncontrolled hypertension).</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Participants Randomized to BHV-0223 First and After a Washout Period of 2-10 Days Received Placebo</title>
          <description>Participants that were randomized to receive sublingual BHV-0223 before performing a 10 minute speech task and were then followed for 3 hours. Participants were then assessed every hour for the next three hours. There was a 2 to 10 days of washout period. These participants would then receive an identical looking sublingual placebo before performing a 10 minute speech task and were followed for 3 hours.</description>
        </group>
        <group group_id="P2">
          <title>Participants Randomized to Placebo First and After a Washout Period of 2-10 Days Received BHV-0223</title>
          <description>Participants that were randomized to receive sublingual placebo before performing a 10 minute speech task and were then followed for 3 hours. Participants were then assessed every hour for the next three hours. There was a 2 to 10 days of washout period. These participants would then receive sublingual BHV-0223 before performing a 10 minute speech task and were followed for 3 hours.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>First Intervention (1 Day)</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Washout (2-10 Days)</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Second Intervention (1 Day)</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="10"/>
              </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>
      <group_list>
        <group group_id="B1">
          <title>Participants That Were Randomized to Receive BHV-0223 (Sublingual Riluzole) First</title>
          <description>Participants were given one dose of BHV-0223 (sublingual riluzole) 35mg before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.&#xD;
BHV-0223: 35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for 3 hours.</description>
        </group>
        <group group_id="B2">
          <title>Participants That Were Randomized to Receive Placebo First</title>
          <description>Participants were given one dose of an identical looking sublingual placebo before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.&#xD;
Placebo: a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for three hours.</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="12"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="22"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</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>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>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="34" lower_limit="18" upper_limit="58"/>
                    <measurement group_id="B2" value="29" lower_limit="20" upper_limit="40"/>
                    <measurement group_id="B3" value="31.7" lower_limit="18" upper_limit="58"/>
                  </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="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="15"/>
                  </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="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Visual Analogue Scale Baseline Score</title>
          <description>In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents &quot;no anxiety&quot; and the right end (100mm) represents &quot;the worst anxiety ever felt&quot; by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum.</description>
          <units>millimeters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="62.25" spread="17.05"/>
                    <measurement group_id="B2" value="46.6" spread="22.5"/>
                    <measurement group_id="B3" value="55.1" spread="20.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>VAS-anxiety Immediately After the Impromptu Speech Task</title>
        <description>Measure Description: In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents &quot;no anxiety&quot; and the right end (100mm) represents &quot;the worst anxiety ever felt&quot; by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum</description>
        <time_frame>up to 60 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BHV-0223 (Sublingual Riluzole)</title>
            <description>Participants will be given one dose of BHV-0223 (sublingual riluzole) 35mg before performing a 10 minute speech task. Participants will then be assessed immediately after finishing speech task.&#xD;
BHV-0223: 35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed immediately after finishing the speech task.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Participants will be given one dose of an identical looking sublingual placebo before performing a 10 minute speech task. Participants will then be assessed immediately after finishing the speech task.&#xD;
Placebo: a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed immediately after finishing the speech task.</description>
          </group>
        </group_list>
        <measure>
          <title>VAS-anxiety Immediately After the Impromptu Speech Task</title>
          <description>Measure Description: In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents &quot;no anxiety&quot; and the right end (100mm) represents &quot;the worst anxiety ever felt&quot; by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum</description>
          <units>millimeters (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="22"/>
                <count group_id="O2" value="22"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.3" spread="23.6"/>
                    <measurement group_id="O2" value="62.6" spread="13.7"/>
                  </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>Paired t-test on VAS scores during speech comparing sublingual riluzole to placebo</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.056</p_value>
            <method>t-test, 2 sided</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-8.34</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>18.34</dispersion_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 1 hour.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>BHV-0223 (Sublingual Riluzole)</title>
          <description>Participants will be given one dose of BHV-0223 (sublingual riluzole) 35mg before performing a 10 minute speech task. Participants will then be assessed immediately after finishing speech task.&#xD;
BHV-0223: 35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed immediately after finishing the speech task.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Participants will be given one dose of an identical looking sublingual placebo before performing a 10 minute speech task. Participants will then be assessed immediately after finishing the speech task.&#xD;
Placebo: a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed immediately after finishing the speech task.</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="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-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="13" subjects_at_risk="22"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="22"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Temporary perioral numbing</sub_title>
                <counts group_id="E1" events="13" subjects_affected="13" subjects_at_risk="22"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="22"/>
              </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>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Angeli Landeros</name_or_title>
      <organization>Yale University</organization>
      <phone>203-737-4809</phone>
      <email>angeli.landeros@yale.edu</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/NCT03017508
org study id: 1605017768
nct id: NCT03017508
lead sponsor: 
collaborator: 
has dmc: No
The goal of the current proposal is to examine if sublingual riluzole can reduce anxiety in
      people with social anxiety disorder during a public speaking task.
The investigators propose conducting a double-blind, placebo controlled crossover study
      examining the effects of BHV-0223 on public speaking anxiety. Twenty participants with DSM-5
      defined social anxiety disorder and clinically significant public speaking anxiety on the
      Impromptu Speech Task will be enrolled in a challenge study. Participants will be given
      BHV-0223 (or placebo) under double-blind crossover conditions 1 hour prior to performing each
      of 2 impromptu speech tasks. The two study days involving BHV-0223 (or placebo)
      administration and impromptu speech task will be separated by 2 to 10 days to allow for
      medication washout. There will be a final follow-up visit 2 to 10 days later to perform a
      complete Physical exam and do follow-up liver function testing and a Complete Blood Count.
      Our primary outcome will examine BHV-0223's effects (compared to placebo) on self-rated
      anxiety during the impromptu speech task. The investigators will also collect physiological
      measures of anxiety, clinician-rated measures of anxiety, and measures of speech performance
      as secondary outcomes.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: VAS-anxiety Immediately After the Impromptu Speech Task
time frame: up to 60 minutes
description: Measure Description: In the Visual Analogue Scale (VAS) participants are presented with a straight horizontal line of 100 mm in length and asked to mark the placement that would best describe the intensity of the anxiety felt at that moment. The left end (0mm) represents "no anxiety" and the right end (100mm) represents "the worst anxiety ever felt" by the participant.The VAS score is determined by measuring in millimeters from the left hand end of the line to the point that the patient marks, generating a numerical score along a continuum
arm group label: BHV-0223 (Sublingual Riluzole)
arm group type: Experimental
description: Participants will be given one dose of BHV-0223 (sublingual riluzole) 35mg before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants will be given one dose of an identical looking sublingual placebo before performing a 10 minute speech task. Participants will then be assessed every hour for the next three hours. There will be 2 to 10 days of washout period between the randomly assigned arms of the study.
intervention type: Drug
intervention name: BHV-0223
description: 35mg of sublingual riluzole before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for 3 hours.
arm group label: BHV-0223 (Sublingual Riluzole)
other name: sublingual riluzole
intervention type: Drug
intervention name: Placebo
description: a sublingual tablet identical to the active drug will be given before performing an anxiety provoking speech task. Participants will then be clinically assessed every hour for three hours.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Michael H. Bloch, MD, MS
role: Principal Investigator
affiliation: Associate Professor
facility: 
country: United States
citation: Davidson JR. Use of benzodiazepines in social anxiety disorder, generalized anxiety disorder, and posttraumatic stress disorder. J Clin Psychiatry. 2004;65 Suppl 5:29-33.
PMID: 15078116
citation: Mathew SJ, Amiel JM, Coplan JD, Fitterling HA, Sackeim HA, Gorman JM. Open-label trial of riluzole in generalized anxiety disorder. Am J Psychiatry. 2005 Dec;162(12):2379-81. doi: 10.1176/appi.ajp.162.12.2379.
PMID: 16330605
citation: Pittenger C, Coric V, Banasr M, Bloch M, Krystal JH, Sanacora G. Riluzole in the treatment of mood and anxiety disorders. CNS Drugs. 2008;22(9):761-86. doi: 10.2165/00023210-200822090-00004.
PMID: 18698875
citation: Sanacora G, Kendell SF, Levin Y, Simen AA, Fenton LR, Coric V, Krystal JH. Preliminary evidence of riluzole efficacy in antidepressant-treated patients with residual depressive symptoms. Biol Psychiatry. 2007 Mar 15;61(6):822-5. doi: 10.1016/j.biopsych.2006.08.037. Epub 2006 Dec 4.
PMID: 17141740
citation: Baker SL, Heinrichs N, Kim HJ, Hofmann SG. The liebowitz social anxiety scale as a self-report instrument: a preliminary psychometric analysis. Behav Res Ther. 2002 Jun;40(6):701-15. doi: 10.1016/s0005-7967(01)00060-2.
PMID: 12051488
citation: Ries BJ, McNeil DW, Boone ML, Turk CL, Carter LE, Heimberg RG. Assessment of contemporary social phobia verbal report instruments. Behav Res Ther. 1998 Oct;36(10):983-94. doi: 10.1016/s0005-7967(98)00078-3.
PMID: 9714948
responsible party type: Sponsor
mesh term: Anxiety Disorders
mesh term: Phobia, Social
mesh term: Riluzole
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 