<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/NCT01688037</url>
  </required_header>
  <id_info>
    <org_study_id>NBI-98854-1201</org_study_id>
    <nct_id>NCT01688037</nct_id>
  </id_info>
  <brief_title>NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder (KINECT Study)</brief_title>
  <official_title>A Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Safety of NBI-98854 for the Treatment of Tardive Dyskinesia in Subjects With Schizophrenia or Schizoaffective Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neurocrine Biosciences</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neurocrine Biosciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate the efficacy, safety, and tolerability of two doses&#xD;
      (50 and 100 mg) of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia&#xD;
      (TD) symptoms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel group&#xD;
      study to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of&#xD;
      NBI-98854 administered once daily for up to 2 weeks. The study will also allow for an&#xD;
      evaluation of the efficacy of NBI-98854 50 mg once daily for up to 6 weeks and the safety and&#xD;
      tolerability of NBI 98854 50 mg once daily for up to 12 weeks.&#xD;
&#xD;
      The double-blind placebo-controlled treatment period the study has three arms:&#xD;
&#xD;
        -  NBI-98854 50 mg once daily for 6 weeks&#xD;
&#xD;
        -  NBI-98854 100 mg once daily for 2 weeks followed by 50 mg once daily for the remaining 4&#xD;
           weeks&#xD;
&#xD;
        -  placebo&#xD;
&#xD;
      At the end of the 6-week placebo-controlled double-blind treatment period, subjects will&#xD;
      continue in the study for an additional 6-week open-label period where all subjects who have&#xD;
      completed the double-blind treatment period will receive NBI-98854 50 mg once daily. Two and&#xD;
      four weeks after the last dose of study drug, follow-up assessments will be performed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">September 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6</measure>
    <time_frame>Baseline and Week 6</time_frame>
    <description>The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Global Improvement of TD (CGI-TD)</measure>
    <time_frame>Week 6</time_frame>
    <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2</measure>
    <time_frame>Week 2</time_frame>
    <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">109</enrollment>
  <condition>Tardive Dyskinesia</condition>
  <arm_group>
    <arm_group_label>NBI-98854 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NBI-98854 50 mg administered as two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NBI-98854 100 mg and 50 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>NBI-98854 100 mg administered as two (2) 50 mg capsules taken every morning between 7:00am - 10:00am for 2 weeks. After 2 weeks, NBI-98854 50 mg administered by two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for remaining 4 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NBI-98854</intervention_name>
    <description>25 mg capsule</description>
    <arm_group_label>NBI-98854 100 mg and 50 mg</arm_group_label>
    <arm_group_label>NBI-98854 50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NBI-98854</intervention_name>
    <description>50 mg capsule</description>
    <arm_group_label>NBI-98854 100 mg and 50 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have a clinical diagnosis of schizophrenia or schizoaffective disorder and a clinical&#xD;
             diagnosis of neuroleptic-induced tardive dyskinesia for at least 3 months prior to&#xD;
             screening.&#xD;
&#xD;
          -  Be receiving a stable dose of antipsychotic medication for a minimum of 30 days before&#xD;
             study start. Subjects who are not using antipsychotic medication must have stable&#xD;
             psychiatric status.&#xD;
&#xD;
          -  Have the doses of concurrent medications and the conditions being treated be stable&#xD;
             for a minimum of 30 days before study start and be expected to remain stable during&#xD;
             the study.&#xD;
&#xD;
          -  Subjects of childbearing potential must agree to use hormonal or two forms of&#xD;
             nonhormonal birth control during the study.&#xD;
&#xD;
          -  Female subjects must not be pregnant.&#xD;
&#xD;
          -  Be in good general health and expected to complete the clinical study as designed.&#xD;
&#xD;
          -  Have a body mass index (BMI) of 18 to 38 kg/m2 (both inclusive).&#xD;
&#xD;
          -  Have a negative urine drug screen (negative for amphetamines, barbiturates,&#xD;
             benzodiazepine, phencyclidine, cocaine, opiates, or cannabinoids) at screening and&#xD;
             study start, except for any subject receiving a stable dose of benzodiazepine.&#xD;
&#xD;
          -  Have a negative alcohol breath test at screening and study start.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have an active clinically significant unstable medical condition within 1 month (30&#xD;
             days) prior to screening.&#xD;
&#xD;
          -  Have a history of substance dependence or substance (drug) or alcohol abuse within the&#xD;
             3 months before study start(nicotine and caffeine dependence are not exclusionary).&#xD;
&#xD;
          -  Have a known history of neuroleptic malignant syndrome.&#xD;
&#xD;
          -  Have a significant risk of suicidal or violent behavior.&#xD;
&#xD;
          -  Receiving any excluded concomitant medication such as reserpine, metoclopramide,&#xD;
             stimulants, or tetrabenazine.&#xD;
&#xD;
          -  Receiving medication for the treatment of tardive dyskinesia.&#xD;
&#xD;
          -  Have a positive human immunodeficiency virus antibody, (HIV-Ab), hepatitis B surface&#xD;
             antigen (HBsAg), or hepatitis C virus (HCV) antibody result at screening or have a&#xD;
             history of positive result.&#xD;
&#xD;
          -  Have received an investigational drug within 30 days before screening or plan to use&#xD;
             an investigational drug (other than NBI-98854) during the study.&#xD;
&#xD;
          -  Have an allergy, hypersensitivity, or intolerance to tetrabenazine.&#xD;
&#xD;
          -  Have had previous exposure with NBI-98854.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chris O'Brien, MD</last_name>
    <role>Study Director</role>
    <affiliation>Neurocrine Biosciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Anaheim</city>
        <state>California</state>
        <zip>92804</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Carson</city>
        <state>California</state>
        <zip>90746</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Colton</city>
        <state>California</state>
        <zip>92324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Costa Mesa</city>
        <state>California</state>
        <zip>92626</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Downey</city>
        <state>California</state>
        <zip>90241</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fountain Valley</city>
        <state>California</state>
        <zip>92708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glendale</city>
        <state>California</state>
        <zip>91206</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>National City</city>
        <state>California</state>
        <zip>91950</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oceanside</city>
        <state>California</state>
        <zip>92056</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Paramount</city>
        <state>California</state>
        <zip>90723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Bernardino</city>
        <state>California</state>
        <zip>92408</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92108</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Santa Ana</city>
        <state>California</state>
        <zip>92705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33334</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33012</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Lauderhill</city>
        <state>Florida</state>
        <zip>33319</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Melbourne</city>
        <state>Florida</state>
        <zip>32901</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Miami Springs</city>
        <state>Florida</state>
        <zip>33166</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>North Miami</city>
        <state>Florida</state>
        <zip>33161</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Orange City</city>
        <state>Florida</state>
        <zip>32763</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Schaumburg</city>
        <state>Illinois</state>
        <zip>60194</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Shreveport</city>
        <state>Louisiana</state>
        <zip>71104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21285</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Glen Burnie</city>
        <state>Maryland</state>
        <zip>21061</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63118</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Brooklyn</city>
        <state>New York</state>
        <zip>11203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Wards Island</city>
        <state>New York</state>
        <zip>10035</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Hope Mills</city>
        <state>North Carolina</state>
        <zip>28348</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Beachwood</city>
        <state>Ohio</state>
        <zip>44122</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Conshohocken</city>
        <state>Pennsylvania</state>
        <zip>19428</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>DeSoto</city>
        <state>Texas</state>
        <zip>75115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Irving</city>
        <state>Texas</state>
        <zip>75062</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Bothell</city>
        <state>Washington</state>
        <zip>98011</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Kirkland</city>
        <state>Washington</state>
        <zip>98033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Spokane</city>
        <state>Washington</state>
        <zip>99204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>Caguas</city>
        <zip>00725</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <address>
        <city>San Juan</city>
        <zip>00927</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 11, 2012</study_first_submitted>
  <study_first_submitted_qc>September 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 19, 2012</study_first_posted>
  <results_first_submitted>May 11, 2017</results_first_submitted>
  <results_first_submitted_qc>October 9, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">November 8, 2017</results_first_posted>
  <disposition_first_submitted>October 2, 2014</disposition_first_submitted>
  <disposition_first_submitted_qc>October 10, 2014</disposition_first_submitted_qc>
  <disposition_first_posted type="Estimate">October 20, 2014</disposition_first_posted>
  <last_update_submitted>October 9, 2017</last_update_submitted>
  <last_update_submitted_qc>October 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dyskinesias</mesh_term>
    <mesh_term>Tardive Dyskinesia</mesh_term>
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tetrabenazine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This study enrolled patients with a clinical diagnosis of schizophrenia or schizoaffective disorder with moderate or severe tardive dyskinesia (TD) from 35 centers in the United States and Puerto Rico. The last patient completed in October 2013.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Double-Blind Placebo, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Double-Blind 50mg, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received valbenazine 50mg capsule once daily for 6 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Double-Blind 100mg/50mg, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Double-Blind Period (Week 0 to 6)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="54"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Open-Label Period (Week 6 to 12)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="47"/>
                <participants group_id="P2" count="25"/>
                <participants group_id="P3" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Non-compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Follow-up Period (Week 12 to 16)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="22"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="42"/>
                <participants group_id="P2" count="21"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Safety analysis set (all randomized subjects who received at least 1 dose of study drug).</population>
      <group_list>
        <group group_id="B1">
          <title>Double-Blind Placebo, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Double-Blind 50mg, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received valbenazine 50mg capsule once daily for 6 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Double-Blind 100mg/50mg, Then Open-Label 50mg</title>
          <description>Double-Blind Period: Participants first received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks.&#xD;
Open-Label Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="B4">
          <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="54"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="27"/>
            <count group_id="B4" value="109"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.5" lower_limit="27" upper_limit="76"/>
                    <measurement group_id="B2" value="55.5" lower_limit="42" upper_limit="72"/>
                    <measurement group_id="B3" value="55.6" lower_limit="28" upper_limit="77"/>
                    <measurement group_id="B4" value="55.0" lower_limit="27" upper_limit="77"/>
                  </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="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="34"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="18"/>
                    <measurement group_id="B4" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or Other Pacific Islander</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaska Native, Black</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Body Mass Index</title>
          <units>kg/m^2</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.71" lower_limit="19.2" upper_limit="44.2"/>
                    <measurement group_id="B2" value="28.85" lower_limit="18.5" upper_limit="42.6"/>
                    <measurement group_id="B3" value="26.39" lower_limit="14.1" upper_limit="37.8"/>
                    <measurement group_id="B4" value="28.17" lower_limit="14.1" upper_limit="44.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at Schizophrenia/Schizoaffective Disorder Diagnosis</title>
          <population>Date of diagnosis was not available for some subjects.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="50"/>
                    <count group_id="B2" value="27"/>
                    <count group_id="B3" value="25"/>
                    <count group_id="B4" value="102"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.4" lower_limit="10" upper_limit="68"/>
                    <measurement group_id="B2" value="29.7" lower_limit="16" upper_limit="66"/>
                    <measurement group_id="B3" value="30.4" lower_limit="17" upper_limit="66"/>
                    <measurement group_id="B4" value="29.7" lower_limit="10" upper_limit="68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age at TD Diagnosis</title>
          <population>Date of diagnosis was not available for some subjects.</population>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="49"/>
                    <count group_id="B2" value="26"/>
                    <count group_id="B3" value="22"/>
                    <count group_id="B4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="46.9" lower_limit="16" upper_limit="73"/>
                    <measurement group_id="B2" value="48.5" lower_limit="37" upper_limit="67"/>
                    <measurement group_id="B3" value="47.5" lower_limit="22" upper_limit="73"/>
                    <measurement group_id="B4" value="47.5" lower_limit="16" upper_limit="73"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>BPRS Total Score</title>
          <description>The Brief Psychiatric Rating Scale (BPRS) is a clinician-rated tool designed to assess change in the severity of psychopathology in patients with schizophrenia and other psychotic disorders (Overall and Gorham, 1962, 1988). The severity of each of the 18 items of the BPRS is rated on a scale of 1 (not present) to 7 (extremely severe) (total score range: 18 to 126). Higher scores represent greater symptom severity.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="54"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="27"/>
                    <count group_id="B4" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="33.8" lower_limit="20" upper_limit="48"/>
                    <measurement group_id="B2" value="32.6" lower_limit="22" upper_limit="49"/>
                    <measurement group_id="B3" value="33.0" lower_limit="21" upper_limit="49"/>
                    <measurement group_id="B4" value="33.3" lower_limit="20" upper_limit="49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Baseline AIMS Total Dyskinesia Score</title>
          <description>The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity.</description>
          <population>Baseline AIMS Total Dyskinesia Score based on the ITT analysis set.</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="54"/>
                    <count group_id="B2" value="27"/>
                    <count group_id="B3" value="26"/>
                    <count group_id="B4" value="107"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="15.3" spread="4.4"/>
                    <measurement group_id="B2" value="14.6" spread="5.9"/>
                    <measurement group_id="B3" value="14.6" spread="4.7"/>
                    <measurement group_id="B4" value="15.0" spread="4.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6</title>
        <description>The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).</description>
        <time_frame>Baseline and Week 6</time_frame>
        <population>Intent to Treat (ITT) analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6). Last observation carried forward (LOCF) imputation method.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.</description>
          </group>
          <group group_id="O2">
            <title>All Valbenazine</title>
            <description>Includes participants who received valbenazine 50mg capsule once daily for 6 weeks and participants who received valbenazine 100mg capsule once daily for 2 weeks, then 50mg capsule once daily for 4 weeks (a total of 6 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6</title>
          <description>The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).</description>
          <population>Intent to Treat (ITT) analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6). Last observation carried forward (LOCF) imputation method.</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="54"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-2.5" spread="0.7"/>
                    <measurement group_id="O2" value="-3.3" spread="0.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.2966</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.8</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.8</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.3</ci_lower_limit>
            <ci_upper_limit>0.7</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression - Global Improvement of TD (CGI-TD)</title>
        <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.</description>
        <time_frame>Week 6</time_frame>
        <population>ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Valbenazine 50mg and Valbenazine 100mg Then 50mg</title>
            <description>Includes participants who received valbenazine 50mg capsule once daily for 6 weeks and participants who received valbenazine 100mg capsule once daily for 2 weeks, then 50mg capsule once daily for 4 weeks (a total of 6 weeks).</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression - Global Improvement of TD (CGI-TD)</title>
          <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.</description>
          <population>ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at either Week 2 or Week 6).</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="54"/>
                <count group_id="O2" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.2" spread="0.1"/>
                    <measurement group_id="O2" value="3.3" spread="0.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.743</p_value>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.1</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3</ci_lower_limit>
            <ci_upper_limit>0.4</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2</title>
        <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).</description>
        <time_frame>Week 2</time_frame>
        <population>ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at Week 2).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Valbenazine 50mg</title>
            <description>Participants received valbenazine 50mg capsule once daily for 2 weeks.</description>
          </group>
          <group group_id="O3">
            <title>Valbenazine 100mg</title>
            <description>Participants received valbenazine 100mg capsule once daily for 2 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2</title>
          <description>Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).</description>
          <population>ITT analysis set (all subjects in the safety analysis set with an evaluable AIMS dyskinesia total score value at Week 2).</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="53"/>
                <count group_id="O2" value="27"/>
                <count group_id="O3" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.6" spread="0.1"/>
                    <measurement group_id="O2" value="3.3" spread="0.2"/>
                    <measurement group_id="O3" value="3.2" spread="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.1151</p_value>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.3</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>0.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Other</non_inferiority_type>
            <p_value>0.0277</p_value>
            <method>ANOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.4</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.2</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.8</ci_lower_limit>
            <ci_upper_limit>0.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 16 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Double-Blind 50mg</title>
          <description>Double-Blind Period: Participants received valbenazine 50mg capsule once daily for 6 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Double-Blind 100mg/50mg</title>
          <description>Double-Blind Period: Participants received valbenazine 100mg capsule once daily for 2 weeks, then they received valbenazine 50mg capsule once daily for 4 weeks.</description>
        </group>
        <group group_id="E3">
          <title>Double-Blind Placebo</title>
          <description>Double-Blind Period: Participants received Placebo capsule (matching valbenazine capsule) once daily for 6 weeks.</description>
        </group>
        <group group_id="E4">
          <title>Open-Label 50mg</title>
          <description>Open-Label Period: Participants who completed the double-blind period entered the open-label period to receive valbenazine 50mg capsule for an additional 6 weeks of treatment.</description>
        </group>
        <group group_id="E5">
          <title>Follow-Up</title>
          <description>Participants who completed the open-label period entered the 4-week follow-up period.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (12.0)</default_vocab>
        <default_assessment>Non-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="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Schizoaffective disorder</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Schizophrenia, paranoid type</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Schizophrenia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
              <event>
                <sub_title>Suicidal ideation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (12.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="93"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E4" events="5" subjects_affected="5" subjects_at_risk="93"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="80"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="93"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="80"/>
              </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>Generally, the PI has the right to publish results provided such publication does not violate confidentiality or IP provisions within the contract with the Sponsor. Prior to submission for publication or presentation of results, the PI must provide the Sponsor time for review. The Sponsor can request the PI to withhold or remove information from all publications. For a multi-center study, any publication of results by the PI shall not be made before the first multi-center publication.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Neurocrine Medical Information</name_or_title>
      <organization>Neurocrine Biosciences, Inc.</organization>
      <phone>877-641-3461</phone>
      <email>medinfo@neurocrine.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/NCT01688037
org study id: NBI-98854-1201
nct id: NCT01688037
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate the efficacy, safety, and tolerability of two doses
      (50 and 100 mg) of NBI-98854 administered once daily for the treatment of Tardive Dyskinesia
      (TD) symptoms.
This is a Phase 2, multicenter, randomized, double-blind, placebo-controlled, parallel group
      study to evaluate the efficacy, safety, and tolerability of two doses (50 and 100 mg) of
      NBI-98854 administered once daily for up to 2 weeks. The study will also allow for an
      evaluation of the efficacy of NBI-98854 50 mg once daily for up to 6 weeks and the safety and
      tolerability of NBI 98854 50 mg once daily for up to 12 weeks.

      The double-blind placebo-controlled treatment period the study has three arms:

        -  NBI-98854 50 mg once daily for 6 weeks

        -  NBI-98854 100 mg once daily for 2 weeks followed by 50 mg once daily for the remaining 4
           weeks

        -  placebo

      At the end of the 6-week placebo-controlled double-blind treatment period, subjects will
      continue in the study for an additional 6-week open-label period where all subjects who have
      completed the double-blind treatment period will receive NBI-98854 50 mg once daily. Two and
      four weeks after the last dose of study drug, follow-up assessments will be performed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Abnormal Involuntary Movement Scale (AIMS) Dyskinesia Total Score Change From Baseline at Week 6
time frame: Baseline and Week 6
description: The AIMS Total Dyskinesia Score rates a total of 7 items, rating involuntary movement from 0 (no dyskinesia) to 4 (severe dyskinesia). Items 1 through 7 include facial and oral movements (Items 1-4), extremity movements (Items 5-6), and trunk movements (Item 7). The AIMS dyskinesia total score for Items 1-7 ranges from 0 to 28; a higher score reflects increased severity. The primary efficacy endpoint was the change from baseline in the AIMS dyskinesia total score at Week 6 between the pooled NBI-98854 50+100 mg group and placebo group analyzed using the ANCOVA model (LOCF, ITT analysis set).
measure: Clinical Global Impression - Global Improvement of TD (CGI-TD)
time frame: Week 6
description: Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse). The ANOVA analysis of CGI-TD was conducted for the pooled NBI-98854 50+100 mg group and placebo group.
measure: Clinical Global Impression - Global Improvement of TD (CGI-TD) at Week 2
time frame: Week 2
description: Clinician's perspective of the participant's overall improvement of TD symptoms over time. The CGI-TD is based on a 7-point scale (range: 1=very much improved to 7=very much worse).
arm group label: NBI-98854 50 mg
arm group type: Experimental
description: NBI-98854 50 mg administered as two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for 6 weeks.
arm group label: NBI-98854 100 mg and 50 mg
arm group type: Experimental
description: NBI-98854 100 mg administered as two (2) 50 mg capsules taken every morning between 7:00am - 10:00am for 2 weeks. After 2 weeks, NBI-98854 50 mg administered by two (2) 25 mg capsules by mouth, taken every morning between 7:00am - 10:00am for remaining 4 weeks.
arm group label: Placebo
arm group type: Placebo Comparator
description: Capsule containing no active substance, manufactured to mimic NBI-98854 25 mg and 50 mg capsules.
intervention type: Drug
intervention name: NBI-98854
description: 25 mg capsule
arm group label: NBI-98854 100 mg and 50 mg
arm group label: NBI-98854 50 mg
intervention type: Drug
intervention name: NBI-98854
description: 50 mg capsule
arm group label: NBI-98854 100 mg and 50 mg
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Chris O'Brien, MD
role: Study Director
affiliation: Neurocrine Biosciences
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country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Dyskinesias
mesh term: Tardive Dyskinesia
mesh term: Schizophrenia
mesh term: Psychotic Disorders
mesh term: Tetrabenazine
participant flow: 
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reported events: 
certain agreements: 
point of contact: 