<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/NCT02195700</url>
  </required_header>
  <id_info>
    <org_study_id>SD-809-C-18</org_study_id>
    <nct_id>NCT02195700</nct_id>
  </id_info>
  <brief_title>Aim to Reduce Movements in Tardive Dyskinesia</brief_title>
  <acronym>ARM-TD</acronym>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled Study of SD-809 (Deutetrabenazine) for the Treatment of Moderate to Severe Tardive Dyskinesia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Auspex Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Teva Branded Pharmaceutical Products R&amp;D, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether an investigational drug, SD-809&#xD;
      (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive&#xD;
      dyskinesia.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 2015</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis</measure>
    <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
    <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)</measure>
    <time_frame>Week 12</time_frame>
    <description>The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)</measure>
    <time_frame>Week 12</time_frame>
    <description>The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)</measure>
    <time_frame>Day 0 (Baseline), Week 12 with last observation carried forward</time_frame>
    <description>The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Participants With Adverse Events for the Overall Treatment Period</measure>
    <time_frame>Day 1 to Week 12</time_frame>
    <description>An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</measure>
    <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
    <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.&#xD;
The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12</measure>
    <time_frame>Day 0 (Baseline), Week 12</time_frame>
    <description>Response level represents the % improvement in AIMS from baseline. AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).&#xD;
Patients with a missing AIMS score were considered to be AIMS nonresponders.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</measure>
    <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
    <description>This outcome is similar to the primary outcome except that AIMS was read locally.&#xD;
AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. This outcome reports the local reading of AIMS data.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">117</enrollment>
  <condition>Tardive Dyskinesia</condition>
  <arm_group>
    <arm_group_label>SD-809</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SD-809 tablets taken twice daily for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar Pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo tablets taken twice daily for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SD-809</intervention_name>
    <description>SD-809 tablets taken twice daily for 12 weeks, includes a dose titration period and maintenance period.</description>
    <arm_group_label>SD-809</arm_group_label>
    <other_name>deutetrabenazine</other_name>
    <other_name>AUSTEDO®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo tablets taken twice daily for 12 weeks.</description>
    <arm_group_label>Sugar Pill</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  History of using a dopamine receptor antagonist for at least 3 months&#xD;
&#xD;
          -  Clinical diagnosis of tardive dyskinesia and has had symptoms for at least 3 months&#xD;
             prior to screening&#xD;
&#xD;
          -  Subjects with underlying psychiatric diagnosis are stable and have no change in&#xD;
             psychoactive medications&#xD;
&#xD;
          -  Have a mental health provider and does not anticipate any changes to treatment regimen&#xD;
             in the next 3 months&#xD;
&#xD;
          -  History of being compliant with prescribed medications&#xD;
&#xD;
          -  Able to swallow study drug whole&#xD;
&#xD;
          -  Be in good general health and is expected to attend all study visits and complete&#xD;
             study assessments&#xD;
&#xD;
          -  Female subjects must not be pregnant and agree to an acceptable method of&#xD;
             contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Currently receiving medication for the treatment of tardive dyskinesia&#xD;
&#xD;
          -  Have a neurological condition other than tardive dyskinesia that may interfere with&#xD;
             assessing the severity of dyskinesias&#xD;
&#xD;
          -  Have a serious untreated or undertreated psychiatric illness&#xD;
&#xD;
          -  Have recent history or presence of violent behavior&#xD;
&#xD;
          -  Have unstable or serious medical illness&#xD;
&#xD;
          -  Have evidence of hepatic impairment&#xD;
&#xD;
          -  Have evidence of renal impairment&#xD;
&#xD;
          -  Have known allergy to any component of SD-809 or tetrabenazine&#xD;
&#xD;
          -  Has participated in an investigational drug or device trial and received study drug&#xD;
             within 30 days&#xD;
&#xD;
          -  Have acknowledged use of illicit drugs&#xD;
&#xD;
          -  Have a history of alcohol or substance abuse in the previous 12 months&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Teva Medical Expert, M.D.</last_name>
    <role>Study Director</role>
    <affiliation>Teva Branded Pharmaceutical Products R&amp;D, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Tuscaloosa</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orange</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Bernardino</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Stamford</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lake City</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Port Charlotte</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Asheville</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Prague</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Gdansk</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Katowice</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Krakow</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lodz</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lublin</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Torun</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hronovce</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Roznava</city>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Czechia</country>
    <country>Poland</country>
    <country>Slovakia</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
  </removed_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>July 18, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 21, 2014</study_first_posted>
  <results_first_submitted>January 3, 2018</results_first_submitted>
  <results_first_submitted_qc>February 19, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">March 20, 2018</results_first_posted>
  <disposition_first_submitted>April 24, 2017</disposition_first_submitted>
  <disposition_first_submitted_qc>April 24, 2017</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">April 25, 2017</disposition_first_posted>
  <last_update_submitted>November 5, 2021</last_update_submitted>
  <last_update_submitted_qc>November 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Dyskinesias</keyword>
  <keyword>Movement Disorders</keyword>
  <keyword>Central Nervous System Diseases</keyword>
  <keyword>Nervous System Diseases</keyword>
  <keyword>Neurologic Manifestations</keyword>
  <keyword>Signs and Symptoms</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyskinesias</mesh_term>
    <mesh_term>Tardive Dyskinesia</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>202 patients were screened and gave informed consent to enter the study. 85 were either ineligible for entry into the study or declined study participation. The most common reason for ineligibility (49 patients) was insufficient TD severity as assessed with Abnormal Involuntary Movement Scale (AIMS). 117 patients were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>SD-809</title>
          <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
        </group>
        <group group_id="P2">
          <title>Placebo</title>
          <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Safety and ITT Populations</title>
              <participants_list>
                <participants group_id="P1" count="58"/>
                <participants group_id="P2" count="59"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Modified ITT Population</title>
              <participants_list>
                <participants group_id="P1" count="56">ITT who received study drug and &gt;=1 centrally read post-baseline AIMS from weeks 2, 4, 6, 9, or 12</participants>
                <participants group_id="P2" count="57">ITT who received study drug and &gt;=1 centrally read post-baseline AIMS from weeks 2, 4, 6, 9, or 12</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Maintenance Period</title>
              <participants_list>
                <participants group_id="P1" count="53"/>
                <participants group_id="P2" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="52"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Noncompliance</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>ITT population</population>
      <group_list>
        <group group_id="B1">
          <title>SD-809</title>
          <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
        </group>
        <group group_id="B2">
          <title>Placebo</title>
          <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</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="58"/>
            <count group_id="B2" value="59"/>
            <count group_id="B3" value="117"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55.9" spread="9.82"/>
                    <measurement group_id="B2" value="53.3" spread="10.64"/>
                    <measurement group_id="B3" value="54.6" spread="10.28"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="56"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="47"/>
                    <measurement group_id="B3" value="100"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</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_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="19"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="44"/>
                    <measurement group_id="B3" value="81"/>
                  </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>
          <title>Education Level</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>=12 years or fewer of formal education</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="30"/>
                    <measurement group_id="B3" value="60"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;12 years of formal education</title>
                  <measurement_list>
                    <measurement group_id="B1" value="28"/>
                    <measurement group_id="B2" value="29"/>
                    <measurement group_id="B3" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Weight</title>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="86.94" spread="24.081"/>
                    <measurement group_id="B2" value="84.95" spread="20.975"/>
                    <measurement group_id="B3" value="85.94" spread="22.493"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Height</title>
          <units>cm</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="169.23" spread="11.462"/>
                    <measurement group_id="B2" value="169.72" spread="10.098"/>
                    <measurement group_id="B3" value="169.48" spread="10.752"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.35" spread="7.926"/>
                    <measurement group_id="B2" value="29.45" spread="6.958"/>
                    <measurement group_id="B3" value="29.89" spread="7.435"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Using a Dopamine Receptor Antagonist (DRA)</title>
          <description>The randomization was stratified by baseline use of DRA (currently taking versus not currently taking a DRA).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Yes</title>
                  <measurement_list>
                    <measurement group_id="B1" value="45"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="94"/>
                  </measurement_list>
                </category>
                <category>
                  <title>No</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="23"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Duration of tardive dyskinesia</title>
          <units>months</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="59"/>
                    <count group_id="B3" value="117"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="72.6" spread="81.65"/>
                    <measurement group_id="B2" value="76.8" spread="82.05"/>
                    <measurement group_id="B3" value="74.7" spread="81.53"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score</title>
          <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This data sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).</description>
          <population>Central reading was not available for one placebo patient.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="58"/>
                    <count group_id="B3" value="116"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.6" spread="4.07"/>
                    <measurement group_id="B2" value="9.6" spread="3.77"/>
                    <measurement group_id="B3" value="9.6" spread="3.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Modified Craniocervical Dystonia Questionnaire (CDQ-24)</title>
          <description>The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. Each of the 24 questions was rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment).</description>
          <population>Baseline CDQ-24 was not completed by two placebo patients.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="58"/>
                    <count group_id="B2" value="57"/>
                    <count group_id="B3" value="115"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.4" spread="20.41"/>
                    <measurement group_id="B2" value="39.7" spread="18.17"/>
                    <measurement group_id="B3" value="39.1" spread="19.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis</title>
        <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.</description>
        <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
        <population>The Modified ITT (mITT) Population was defined as all patients in the ITT Population who received study drug and had at least 1 centrally read post-baseline assessment of the AIMS from at least 1 scheduled post-baseline time point. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis</title>
          <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.</description>
          <population>The Modified ITT (mITT) Population was defined as all patients in the ITT Population who received study drug and had at least 1 centrally read post-baseline assessment of the AIMS from at least 1 scheduled post-baseline time point. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-3.0" spread="0.45"/>
                    <measurement group_id="O2" value="-1.6" spread="0.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The linear mixed model for repeated measurements (MMRM) included fixed effects for treatment, each scheduled time point (5 levels: weeks 2, 4, 6, 9, and 12), the treatment-by-time point interaction, and the DRA status. Baseline AIMS score was a covariate. The unstructured covariance model was used, and the primary analysis compared the SD-809 and placebo groups at week 12. This was based on the F-test using the Satterhwaite method to compute the denominator degrees of freedom.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0188</p_value>
            <p_value_desc>5% level of significance (2-sided)</p_value_desc>
            <method>unstructured covariance</method>
            <param_type>LSM difference</param_type>
            <param_value>-1.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.60</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.6</ci_lower_limit>
            <ci_upper_limit>-0.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)</title>
        <description>The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
        <time_frame>Week 12</time_frame>
        <population>modified intent to treat population</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)</title>
          <description>The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
          <population>modified intent to treat population</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="56"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.2"/>
                    <measurement group_id="O2" value="40.4"/>
                  </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>The secondary efficacy endpoints were analyzed using a hierarchical testing procedure. If the primary analysis was statistically significant (p&lt;0.05), then the first key secondary endpoint was to be analyzed. If the first key secondary endpoint was statistically significant, then the second key secondary endpoint was to be similarly analyzed. For any analysis that was not statistically significant, all subsequent analyses of key secondary endpoints were exploratory rather than confirmatory.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4001</p_value>
            <p_value_desc>5% level of significance (2-sided)</p_value_desc>
            <method>Pearson's chi-square test</method>
            <param_type>Differences in %</param_type>
            <param_value>7.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-10.2</ci_lower_limit>
            <ci_upper_limit>25.2</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)</title>
        <description>The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
        <time_frame>Week 12</time_frame>
        <population>modified intent to treat population</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)</title>
          <description>The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not &quot;much improved&quot; or &quot;very much improved&quot; at the week 12 visit, were considered treatment failures.</description>
          <population>modified intent to treat population</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="56"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.9"/>
                    <measurement group_id="O2" value="29.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)</title>
        <description>The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.</description>
        <time_frame>Day 0 (Baseline), Week 12 with last observation carried forward</time_frame>
        <population>modified intent to treat population</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)</title>
          <description>The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.</description>
          <population>modified intent to treat population</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="56"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.1" spread="2.14"/>
                    <measurement group_id="O2" value="-8.3" spread="2.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Participants With Adverse Events for the Overall Treatment Period</title>
        <description>An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.</description>
        <time_frame>Day 1 to Week 12</time_frame>
        <population>Safety population</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Participants With Adverse Events for the Overall Treatment Period</title>
          <description>An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.</description>
          <population>Safety population</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="58"/>
                <count group_id="O2" value="59"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Overall Treatment Period: any AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41"/>
                    <measurement group_id="O2" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Treatment Period: SAE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Treatment Period: Severe AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Treatment Period: treatment-related AE</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28"/>
                    <measurement group_id="O2" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Overall Treatment Period: Deaths</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</title>
        <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.&#xD;
The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.</description>
        <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
        <population>modified intent to treat population. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</title>
          <description>AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.&#xD;
The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.</description>
          <population>modified intent to treat population. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
          <units>percentage change</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-26.7" spread="6.06"/>
                    <measurement group_id="O2" value="-15.5" spread="6.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12</title>
        <description>Response level represents the % improvement in AIMS from baseline. AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).&#xD;
Patients with a missing AIMS score were considered to be AIMS nonresponders.</description>
        <time_frame>Day 0 (Baseline), Week 12</time_frame>
        <population>modified intent to treat population.</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12</title>
          <description>Response level represents the % improvement in AIMS from baseline. AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).&#xD;
Patients with a missing AIMS score were considered to be AIMS nonresponders.</description>
          <population>modified intent to treat population.</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="56"/>
                <count group_id="O2" value="57"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>&gt;=10%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="69.6"/>
                    <measurement group_id="O2" value="42.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=20%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="50.0"/>
                    <measurement group_id="O2" value="29.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=30%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="46.4"/>
                    <measurement group_id="O2" value="24.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=40%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.1"/>
                    <measurement group_id="O2" value="22.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=50%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.2"/>
                    <measurement group_id="O2" value="17.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=60%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6"/>
                    <measurement group_id="O2" value="8.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=70%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.7"/>
                    <measurement group_id="O2" value="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=80%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9"/>
                    <measurement group_id="O2" value="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>&gt;=90%</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6"/>
                    <measurement group_id="O2" value="1.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</title>
        <description>This outcome is similar to the primary outcome except that AIMS was read locally.&#xD;
AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. This outcome reports the local reading of AIMS data.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.</description>
        <time_frame>Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12</time_frame>
        <population>modified intent to treat analysis. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
        <group_list>
          <group group_id="O1">
            <title>SD-809</title>
            <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
          <group group_id="O2">
            <title>Placebo</title>
            <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis</title>
          <description>This outcome is similar to the primary outcome except that AIMS was read locally.&#xD;
AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. This outcome reports the local reading of AIMS data.&#xD;
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.&#xD;
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.</description>
          <population>modified intent to treat analysis. Number analyzed includes participants who had week 12 readings minus one placebo patient missing a baseline reading.</population>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4.9" spread="0.64"/>
                    <measurement group_id="O2" value="-3.7" spread="0.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1 to Week 12</time_frame>
      <group_list>
        <group group_id="E1">
          <title>SD-809</title>
          <description>Patients underwent dose adjustment of SD-809 over the initial 6 weeks of treatment, starting treatment with SD-809 at 6 mg twice daily and titrating to a maximum total daily dose of 48 mg per day. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout.&#xD;
Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
        </group>
        <group group_id="E2">
          <title>Placebo</title>
          <description>Patients underwent 'dose adjustment' of placebo over the initial 6 weeks of treatment. The optimal dose was continued by a 6-week maintenance period, which was followed by a 1-week washout. Patients who completed the study had the option to rollover into a long-term safety study (Study SD-809-C-20, NCT02198794). For patients who did not enter the long-term safety study, there was an additional 3-week safety follow-up period after treatment.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Abscess jaw</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Jaw fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Mania</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Laryngeal hypertrophy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (17.0)</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="24" subjects_at_risk="58"/>
                <counts group_id="E2" subjects_affected="26" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="4" subjects_affected="3" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="5" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="58"/>
                <counts group_id="E2" events="8" subjects_affected="6" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Akathisia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="58"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="58"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="59"/>
              </event>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="58"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="59"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="58"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="59"/>
              </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>Sponsor has the right 60 days before submission for publication to review/provide comments. If the Sponsor's review shows that potentially patentable subject matter would be disclosed, publication or public disclosure shall be delayed for up to 90 additional days in order for the Sponsor, or Sponsor's designees, to file the necessary patent applications. In multicenter trials, each PI will postpone single center publications until after disclosure or publication of multicenter data.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Director, Clinical Research</name_or_title>
      <organization>Teva Branded Pharmaceutical Products, R&amp;D Inc</organization>
      <phone>215-591-3000</phone>
      <email>ustevatrials@tevapharm.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/NCT02195700
org study id: SD-809-C-18
nct id: NCT02195700
lead sponsor: 
has dmc: Yes
The purpose of this study is to determine whether an investigational drug, SD-809
      (deutetrabenazine), will reduce the severity of abnormal involuntary movements of tardive
      dyskinesia.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using Mixed Model Repeated Measures (MMRM) Analysis
time frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
description: AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point, treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. An unstructured covariance model was used.
measure: Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Clinical Global Impression of Change (CGIC)
time frame: Week 12
description: The CGIC is a single-item questionnaire that asks the investigator to assess a patient's TD symptoms at specific visits after initiating therapy. The CGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.
measure: Percentage of Patients Who Are a Treatment Success at Week 12 as Assessed by the Patient Global Impression of Change (PGIC)
time frame: Week 12
description: The PGIC is a single-item questionnaire that asks the patient to assess their TD symptoms at specific visits after initiating therapy. The PGIC uses a 7 point Likert Scale, ranging from very much worse (-3) to very much improved (+3), to assess overall response to therapy. A treatment success was defined as "much improved" or "very much improved" at the week 12 visit. Patients whose status at week 12 was not known, as well as patients who were not "much improved" or "very much improved" at the week 12 visit, were considered treatment failures.
measure: Change From Baseline to Week 12 in the Modified Craniocervical Dystonia Questionnaire (CDQ-24)
time frame: Day 0 (Baseline), Week 12 with last observation carried forward
description: The CDQ-24 is a disease-specific quality of life questionnaire developed for use in patients with craniocervical dystonia, including both cervical dystonia (CD) and blepharospasm (BPS). The CDQ 24 was modified such that the questions focus more directly on the impact of TD (as opposed to CD/BPS) on quality of life. The following domains are evaluated in the CDQ-24: stigma, emotional well-being, pain, activities of daily living, and social/family life. Each of the 24 questions were rated by patients on a scale of 0=no impairment to 4=severest impairment for a total scale of 0 (no impairment) to 96 (severe impairment). Negative change from baseline scores indicate improvement.
measure: Participants With Adverse Events for the Overall Treatment Period
time frame: Day 1 to Week 12
description: An adverse event was defined as any untoward medical occurrence that develops or worsens in severity during the conduct of a clinical study and does not necessarily have a causal relationship to the study drug. Severity was rated by the investigator on a scale of mild, moderate and severe, with severe= an AE which prevents normal daily activities. Relation of AE to treatment was determined by the investigator and includes possibly, probably and definitely related categories. Serious AEs (SAE) include death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, OR an important medical event that jeopardized the patient and required medical intervention to prevent the previously listed serious outcomes.
measure: Percentage Change in Centrally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
time frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
description: AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative percent change from baseline score indicates improvement.
The MMRM model includes fixed effects for treatment, time point (weeks 2, 4, 6, 9, 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate. Patient is a random effect.
measure: Cumulative Percentage of Abnormal Involuntary Movement Scale (AIMS) Responders by Response Level (Percentage Improvement From Baseline) at Week 12
time frame: Day 0 (Baseline), Week 12
description: Response level represents the % improvement in AIMS from baseline. AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. AIMS was digitally video recorded using a standard protocol and independently reviewed by blinded central raters who were experts in movement disorders.
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia).
Patients with a missing AIMS score were considered to be AIMS nonresponders.
measure: Change in Locally Read Abnormal Involuntary Movement Scale (AIMS) Score From Baseline to Week 12 Using MMRM Analysis
time frame: Day 0 (Baseline), Weeks 2, 4, 6, 9 and 12
description: This outcome is similar to the primary outcome except that AIMS was read locally.
AIMS is an assessment tool used to detect and follow the severity of TD over time. The AIMS is composed of 12 clinician-administered and scored items. This outcome reports the local reading of AIMS data.
This outcome sums items 1 through 7 which cover orofacial movements, and extremity and truncal dyskinesia. Severity ratings were from 0 (none) to 4 (severe) for a total scale of 0 (no orofacial, truncal, and extremity dyskinesia) to 28 (severe orofacial, truncal, and extremity dyskinesia). A negative change from baseline score indicates improvement.
A MMRM analysis with change from baseline in AIMS score as dependent variable was used. The model included fixed effects for treatment, time point (weeks 2, 4, 6, 9, and 12), treatment-by-time point interaction, DRA status, and baseline AIMS as a covariate.
arm group label: SD-809
arm group type: Experimental
description: SD-809 tablets taken twice daily for 12 weeks.
arm group label: Sugar Pill
arm group type: Placebo Comparator
description: Placebo tablets taken twice daily for 12 weeks.
intervention type: Drug
intervention name: SD-809
description: SD-809 tablets taken twice daily for 12 weeks, includes a dose titration period and maintenance period.
arm group label: SD-809
other name: deutetrabenazine
other name: AUSTEDO®
intervention type: Drug
intervention name: Placebo
description: Placebo tablets taken twice daily for 12 weeks.
arm group label: Sugar Pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Teva Medical Expert, M.D.
role: Study Director
affiliation: Teva Branded Pharmaceutical Products R&D, Inc.
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country: Czechia
country: Poland
country: Slovakia
country: United States
country: Czech Republic
responsible party type: Sponsor
mesh term: Dyskinesias
mesh term: Tardive Dyskinesia
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 