<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/NCT01668667</url>
  </required_header>
  <id_info>
    <org_study_id>114025</org_study_id>
    <nct_id>NCT01668667</nct_id>
  </id_info>
  <brief_title>Gabapentin Enacarbil (GSK1838262) Adult Restless Leg Syndrome (RLS) Post Marketing Commitment Study</brief_title>
  <acronym>CONCORD</acronym>
  <official_title>Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Parallel-Group Study to Compare the Efficacy, Tolerability, and Safety of 3 Doses of Gabapentin Enacarbil (GSK1838262) With Placebo in Treatment of Moderate-to-Severe Primary RLS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>XenoPort, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>XenoPort, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Gabapentin enacarbil (GEn; GSK1838262; HORIZANT), at a dose of 600 mg/day, is currently&#xD;
      approved in the United States for the treatment of adults with moderate-to-severe primary&#xD;
      Restless Legs Syndrome (RLS). The aim of this study is to compare the efficacy, tolerability,&#xD;
      and safety of GEn at lower doses (450 and 300 mg/day) as well as the already approved dose of&#xD;
      600 mg/day versus placebo for the treatment of subjects with moderate to severe primary RLS.&#xD;
      This study is being conducted as a post-marketing commitment (PMC) as a condition of the&#xD;
      approval of HORIZANT tablets (NDA 022399).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase IV randomized, double-blind, placebo-controlled, fixed-dose, parallel group&#xD;
      study to assess the efficacy, tolerability, and safety of 3 doses of GEn (600, 450, and 300&#xD;
      mg/day) compared with placebo in the treatment of subjects with moderate-to-severe primary&#xD;
      RLS.&#xD;
&#xD;
      The study will include 9 visits over approximately 14 weeks for eligible subjects including a&#xD;
      1-week Screening Period, a 12-week Treatment Period, and a 1 week Follow up Period. Screening&#xD;
      will occur within 1 week of the first scheduled dose of study medication. The total duration&#xD;
      of the study, from the first subject enrolled to the last subject completed will be&#xD;
      approximately 2 years.&#xD;
&#xD;
      Eligible subjects (at least 18 years of age) must have:&#xD;
&#xD;
        -  a diagnosis of RLS according to the IRLSSG Diagnostic Criteria&#xD;
&#xD;
        -  a history of RLS symptoms for at least 15 nights in the prior month or, if on treatment,&#xD;
           this frequency of symptoms before treatment was started&#xD;
&#xD;
        -  documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights during the&#xD;
           Screening Period, and a total RLS severity score of at least 15 on the International&#xD;
           Restless Legs Syndrome (IRLS) Rating Scale at the screening and baseline visits&#xD;
&#xD;
      Approximately 498 subjects will be enrolled, randomly assigned to treatment groups, and&#xD;
      receive study medication once daily for 12 weeks. Subjects will be randomly assigned to&#xD;
      receive 1 of the 4 following treatment groups in a ratio of 1:1:1:1:&#xD;
&#xD;
        -  GEn 600 mg/day&#xD;
&#xD;
        -  GEn 450 mg/day&#xD;
&#xD;
        -  GEn 300 mg/day&#xD;
&#xD;
        -  Matching placebo&#xD;
&#xD;
      Subjects will be instructed to take their study medication once daily with food in the&#xD;
      evening at approximately 5 PM. Each tablet must be swallowed whole and not divided, crushed,&#xD;
      or chewed.&#xD;
&#xD;
      Each subject, regardless of treatment assignment, will take 3 tablets of study medication (1&#xD;
      tablet from Bottle A, 1 tablet from Bottle B, and 1 tablet from Bottle C) once daily&#xD;
      continuing through the end of the Treatment Period (Week 12). Subjects will return to the&#xD;
      study site for a follow-up visit (Visit 9, Week 13) approximately 1 week after the last dose&#xD;
      of study medication.&#xD;
&#xD;
      Each subject's participation in the study will be approximately 14 weeks unless they withdraw&#xD;
      early from the study. For subjects who complete the study, Visit 9 (which can occur between&#xD;
      Day 86 and 92) will be considered their end-of-study visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>June 2012</start_date>
  <completion_date type="Actual">November 2013</completion_date>
  <primary_completion_date type="Actual">November 2013</primary_completion_date>
  <phase>Phase 4</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>The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score</measure>
    <time_frame>Baseline, 12 weeks</time_frame>
    <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo.&#xD;
The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The Proportion of Subjects at the End of Treatment Who Are Responders With Either &quot;Much Improved&quot; or &quot;Very Much Improved&quot; on the Investigator-rated Clinical Global Impression of Improvement (CGI-I)</measure>
    <time_frame>12 weeks</time_frame>
    <description>Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment</measure>
    <time_frame>Baseline, 12 Weeks</time_frame>
    <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
This model only includes treatment in the model. Least squares mean is used for analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment</measure>
    <time_frame>12 Weeks</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">501</enrollment>
  <condition>Restless Legs Syndrome</condition>
  <arm_group>
    <arm_group_label>GSK1838262 600 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once-daily dose with food in the evening at approximately 5 PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GSK1838262 450 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once-daily dose with food in the evening at approximately 5 PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GSK1838262 300 mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Once-daily dose with food in the evening at approximately 5 PM</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GSK1838262 placebo match</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Once-daily dose with food in the evening at approximately 5 PM</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK1838262 600 mg</intervention_name>
    <description>Drug: GSK1838262 600 mg/day Comparison of 3 doses</description>
    <arm_group_label>GSK1838262 600 mg</arm_group_label>
    <other_name>Horizant</other_name>
    <other_name>gabapentin enacarbil GEn</other_name>
    <other_name>XP13512</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK1838262 450 mg</intervention_name>
    <description>Drug: GSK1838262 450 mg/day Comparison of 3 doses</description>
    <arm_group_label>GSK1838262 450 mg</arm_group_label>
    <other_name>Horizant</other_name>
    <other_name>gabapentin enacarbil GEn</other_name>
    <other_name>XP13512</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK1838262 300 mg</intervention_name>
    <description>Drug: GSK1838262 300 mg/day Comparison of 3 doses</description>
    <arm_group_label>GSK1838262 300 mg</arm_group_label>
    <other_name>Horizant</other_name>
    <other_name>gabapentin enacarbil GEn</other_name>
    <other_name>XP13512</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK1838262 Placebo match</intervention_name>
    <description>Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses</description>
    <arm_group_label>GSK1838262 placebo match</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men or women 18 years of age or older&#xD;
&#xD;
          -  History of RLS symptoms for at least 15 nights/month&#xD;
&#xD;
          -  Documented RLS symptoms, using the 7-day RLS Symptom Record, for at least 4 of the 7&#xD;
             consecutive evenings/nights during the night&#xD;
&#xD;
          -  Total RLS severity score of 15 or greater on the International RLS (IRLS) Rating Scale&#xD;
             at Visit 1 and at Visit 2&#xD;
&#xD;
          -  Discontinuation of dopamine agonists and/or gabapentin , or other treatments for RLS&#xD;
             (e.g. opioids, benzodiazepines) at least 2 weeks prior to Baseline&#xD;
&#xD;
          -  If taking any prescription medication, therapy must have been stabilized for at least&#xD;
             3 months prior to Screening with no anticipated changes for the duration of the study&#xD;
&#xD;
          -  Female subjects are eligible if of non-childbearing potential or not lactating, has a&#xD;
             negative pregnancy, and agrees to use a highly effective method for avoiding pregnancy&#xD;
&#xD;
          -  Body mass index of 34 or below&#xD;
&#xD;
          -  Estimated creatinine clearance of ≥60 mL/min&#xD;
&#xD;
          -  Provides written consent in accordance with all applicable regulatory requirements&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of a sleep disorder that may affect the assessment of RLS&#xD;
&#xD;
          -  History of RLS symptom augmentation or end-of-dose rebound with previous dopamine&#xD;
             agonist treatment&#xD;
&#xD;
          -  Neurologic disease or movement disorder&#xD;
&#xD;
          -  Other medical conditions or drug therapy that could affect RLS efficacy assessments or&#xD;
             may present a safety concern&#xD;
&#xD;
          -  Have clinically significant or unstable medical conditions&#xD;
&#xD;
          -  Have active suicidal plan/intent or has had active suicidal thoughts in the past 6&#xD;
             months; has a history of suicide attempt&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85020</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85050</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>85704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80907</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>DeLand</city>
        <state>Florida</state>
        <zip>32720</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33609</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30342</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Woodstock</city>
        <state>Georgia</state>
        <zip>30189</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lenexa</city>
        <state>Kansas</state>
        <zip>66214</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <zip>66606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Crestview Hills</city>
        <state>Kentucky</state>
        <zip>41017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40217</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Metairie</city>
        <state>Louisiana</state>
        <zip>70006</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Chevy Chase</city>
        <state>Maryland</state>
        <zip>20815</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bingham Farms</city>
        <state>Michigan</state>
        <zip>48025</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68134</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Hickory</city>
        <state>North Carolina</state>
        <zip>28601</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45255</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Middleburg Heights</city>
        <state>Ohio</state>
        <zip>44130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Lafayette Hill</city>
        <state>Pennsylvania</state>
        <zip>19444</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Warwick</city>
        <state>Rhode Island</state>
        <zip>02886</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Greer</city>
        <state>South Carolina</state>
        <zip>29651</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Mount Pleasant</city>
        <state>South Carolina</state>
        <zip>29464</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Jackson</city>
        <state>Tennessee</state>
        <zip>38305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <zip>78731</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <zip>76135</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Angelo</city>
        <state>Texas</state>
        <zip>76904</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84123</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22911</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>June 14, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 20, 2012</study_first_posted>
  <results_first_submitted>July 14, 2014</results_first_submitted>
  <results_first_submitted_qc>November 10, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 17, 2014</results_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>gabapentin enacarbil</keyword>
  <keyword>Horizant</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychomotor Agitation</mesh_term>
    <mesh_term>Restless Legs Syndrome</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Gabapentin</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>GSK1838262 600 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="P2">
          <title>GSK1838262 450 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="P3">
          <title>GSK1838262 300 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="P4">
          <title>GSK1838262 Placebo Match</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="126"/>
                <participants group_id="P2" count="125"/>
                <participants group_id="P3" count="125"/>
                <participants group_id="P4" count="125"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="95"/>
                <participants group_id="P2" count="99"/>
                <participants group_id="P3" count="94"/>
                <participants group_id="P4" count="102"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="26"/>
                <participants group_id="P3" count="31"/>
                <participants group_id="P4" count="23"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="7"/>
                <participants group_id="P4" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
      <group_list>
        <group group_id="B1">
          <title>GSK1838262 600 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="B2">
          <title>GSK1838262 450 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="B3">
          <title>GSK1838262 300 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="B4">
          <title>GSK1838262 Placebo Match</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="B5">
          <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="119"/>
            <count group_id="B2" value="112"/>
            <count group_id="B3" value="111"/>
            <count group_id="B4" value="117"/>
            <count group_id="B5" value="459"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="49.2" spread="12.92"/>
                    <measurement group_id="B2" value="52.1" spread="12.22"/>
                    <measurement group_id="B3" value="52.0" spread="14.51"/>
                    <measurement group_id="B4" value="52.1" spread="13.01"/>
                    <measurement group_id="B5" value="51.3" spread="13.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="73"/>
                    <measurement group_id="B2" value="69"/>
                    <measurement group_id="B3" value="71"/>
                    <measurement group_id="B4" value="64"/>
                    <measurement group_id="B5" value="277"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="43"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="53"/>
                    <measurement group_id="B5" value="182"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>African American/African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="8"/>
                    <measurement group_id="B5" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>American Indian or Alaskan Native</title>
              <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="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Native Hawaiian or other Pacific Islander</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="112"/>
                    <measurement group_id="B2" value="97"/>
                    <measurement group_id="B3" value="95"/>
                    <measurement group_id="B4" value="109"/>
                    <measurement group_id="B5" value="413"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White &amp; African American/African Heritage</title>
              <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="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White &amp; Asian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Unknown or not Reported</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>IRLS Rating Scale Total Score, Continuous</title>
          <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="23.4" spread="5.61"/>
                    <measurement group_id="B2" value="24.0" spread="5.23"/>
                    <measurement group_id="B3" value="23.7" spread="5.25"/>
                    <measurement group_id="B4" value="23.5" spread="5.34"/>
                    <measurement group_id="B5" value="23.6" spread="5.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score</title>
        <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo.&#xD;
The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.</description>
        <time_frame>Baseline, 12 weeks</time_frame>
        <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
        <group_list>
          <group group_id="O1">
            <title>GSK1838262 600 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O2">
            <title>GSK1838262 450 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O3">
            <title>GSK1838262 300 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O4">
            <title>GSK1838262 Placebo Match</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score</title>
          <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo.&#xD;
The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.</description>
          <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="119"/>
                <count group_id="O2" value="112"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.50" spread="0.745"/>
                    <measurement group_id="O2" value="-12.54" spread="0.764"/>
                    <measurement group_id="O3" value="-11.48" spread="0.767"/>
                    <measurement group_id="O4" value="-9.93" spread="0.753"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the change from Baseline to the end of treatment in the IRLS Rating Scale total score. All comparisons will be made at the two-sided 0.05 level of significance.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.014</p_value>
            <method>ANCOVA</method>
            <method_desc>No adjustment for multiplicity will be made for these analyses.</method_desc>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-2.57</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.745</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.62</ci_lower_limit>
            <ci_upper_limit>-0.52</ci_upper_limit>
            <estimate_desc>The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the change from Baseline to the end of treatment in the IRLS Rating Scale total score. All comparisons will be made at the two-sided 0.05 level of significance.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.014</p_value>
            <method>ANCOVA</method>
            <method_desc>No adjustment for multiplicity will be made for these analyses.</method_desc>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-2.61</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.764</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-4.68</ci_lower_limit>
            <ci_upper_limit>-0.54</ci_upper_limit>
            <estimate_desc>The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the change from Baseline to the end of treatment in the IRLS Rating Scale total score. All comparisons will be made at the two-sided 0.05 level of significance.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.144</p_value>
            <method>ANCOVA</method>
            <method_desc>No adjustment for multiplicity will be made for these analyses.</method_desc>
            <param_type>Adjusted mean difference</param_type>
            <param_value>-1.55</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.767</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-3.63</ci_lower_limit>
            <ci_upper_limit>0.53</ci_upper_limit>
            <estimate_desc>The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>The Proportion of Subjects at the End of Treatment Who Are Responders With Either &quot;Much Improved&quot; or &quot;Very Much Improved&quot; on the Investigator-rated Clinical Global Impression of Improvement (CGI-I)</title>
        <description>Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.</description>
        <time_frame>12 weeks</time_frame>
        <population>mITT (modified intent to treat) population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
        <group_list>
          <group group_id="O1">
            <title>GSK1838262 600 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O2">
            <title>GSK1838262 450 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O3">
            <title>GSK1838262 300 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O4">
            <title>GSK1838262 Placebo Match</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Proportion of Subjects at the End of Treatment Who Are Responders With Either &quot;Much Improved&quot; or &quot;Very Much Improved&quot; on the Investigator-rated Clinical Global Impression of Improvement (CGI-I)</title>
          <description>Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.</description>
          <population>mITT (modified intent to treat) population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</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="119"/>
                <count group_id="O2" value="112"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67"/>
                    <measurement group_id="O2" value="67"/>
                    <measurement group_id="O3" value="68"/>
                    <measurement group_id="O4" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the proportion of subjects who are responders with &quot;much improved&quot; or &quot;very much improved&quot; on the investigator-rated CGI-I at the end of treatment.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.004</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.26</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.30</ci_lower_limit>
            <ci_upper_limit>3.95</ci_upper_limit>
            <estimate_desc>The analysis method used was logistic regression with terms of pooled site and treatment.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the proportion of subjects who are responders with &quot;much improved&quot; or &quot;very much improved&quot; on the investigator-rated CGI-I at the end of treatment.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.007</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.15</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.23</ci_lower_limit>
            <ci_upper_limit>3.77</ci_upper_limit>
            <estimate_desc>The analysis method used was logistic regression with terms of pooled site and treatment.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>The null hypothesis for this study is that there is no difference between GEn and placebo in the proportion of subjects who are responders with &quot;much improved&quot; or &quot;very much improved&quot; on the investigator-rated CGI-I at the end of treatment.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.005</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.24</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.27</ci_lower_limit>
            <ci_upper_limit>3.94</ci_upper_limit>
            <estimate_desc>The analysis method used was logistic regression with terms of pooled site and treatment.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment</title>
        <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
This model only includes treatment in the model. Least squares mean is used for analysis.</description>
        <time_frame>Baseline, 12 Weeks</time_frame>
        <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
        <group_list>
          <group group_id="O1">
            <title>GSK1838262 600 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O2">
            <title>GSK1838262 450 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O3">
            <title>GSK1838262 300 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O4">
            <title>GSK1838262 Placebo Match</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment</title>
          <description>International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.&#xD;
This model only includes treatment in the model. Least squares mean is used for analysis.</description>
          <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</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="119"/>
                <count group_id="O2" value="112"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-12.1" spread="0.80"/>
                    <measurement group_id="O2" value="-12.7" spread="0.82"/>
                    <measurement group_id="O3" value="-11.3" spread="0.83"/>
                    <measurement group_id="O4" value="-9.8" spread="0.80"/>
                  </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>O3</group_id>
            </group_id_list>
            <groups_desc>For the mean change from Baseline for IRLS Rating Scale total score at the EOT, the linear contrast test based on an analysis of variance with treatment effect was used to detect linear dose-response trends across increasing levels of GEn dosage.</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.022</p_value>
            <method>ANOVA</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Overall treatment effect</groups_desc>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.072</p_value>
            <method>ANOVA</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment</title>
        <time_frame>12 Weeks</time_frame>
        <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</population>
        <group_list>
          <group group_id="O1">
            <title>GSK1838262 600 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O2">
            <title>GSK1838262 450 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O3">
            <title>GSK1838262 300 mg</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
          <group group_id="O4">
            <title>GSK1838262 Placebo Match</title>
            <description>Once-daily dose with food in the evening at approximately 5 PM</description>
          </group>
        </group_list>
        <measure>
          <title>The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment</title>
          <population>mITT (modified intent to treat) Population: The mITT population will include all randomly assigned subjects who received at least 1 dose (or any portion of a dose) of study medication as defined above for the Safety population, have a baseline IRLS Rating Scale total score, and have at least 1 on-treatment IRLS Rating Scale total score.</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="119"/>
                <count group_id="O2" value="112"/>
                <count group_id="O3" value="111"/>
                <count group_id="O4" value="117"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Responder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="67"/>
                    <measurement group_id="O2" value="67"/>
                    <measurement group_id="O3" value="68"/>
                    <measurement group_id="O4" value="50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Non-Responder</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="33"/>
                    <measurement group_id="O3" value="32"/>
                    <measurement group_id="O4" value="50"/>
                  </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>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority or Other (legacy)</non_inferiority_type>
            <p_value>0.012</p_value>
            <p_value_desc>A significant p-value will indicate a nonzero linear effect across increasing levels of GEn dosage.</p_value_desc>
            <method>Cochran-Armitage trend test</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>AEs are collected from the start of study medication and until the follow-up contact. SAEs are collected over the same time period as AEs. SAEs related to study participation are recorded from the time of consenting up to &amp; including any follow-up contact</time_frame>
      <desc>All safety summaries were based on Safety Population, which was defined as all subjects who received at least 1 dose or any portion of a dose of study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>GSK1838262 600 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="E2">
          <title>GSK1838262 450 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="E3">
          <title>GSK1838262 300 mg</title>
          <description>Once-daily dose with food in the evening at approximately 5 PM</description>
        </group>
        <group group_id="E4">
          <title>GSK1838262 Placebo Match</title>
          <description>Once-daily dose with food in the evening at approximately 5 PMmatching placebo.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <description>Unrelated treatment emergent SAE</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Ligament rupture</sub_title>
                <description>Unrelated treatment emergent SAE</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Alcohol withdrawal syndrome</sub_title>
                <description>Unrelated treatment emergent SAE</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <description>Unrelated treatment emergent SAE</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA</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="55" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="56" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="46" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="20" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="12" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="10" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="12" subjects_at_risk="121"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="121"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <description>Treatment Emergent AE</description>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="122"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="123"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="121"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="121"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>XenoPort Call Center</name_or_title>
      <organization>XenoPort, Inc.</organization>
      <phone>877-936-6778</phone>
    </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/NCT01668667
org study id: 114025
nct id: NCT01668667
lead sponsor: 
has dmc: No
Gabapentin enacarbil (GEn; GSK1838262; HORIZANT), at a dose of 600 mg/day, is currently
      approved in the United States for the treatment of adults with moderate-to-severe primary
      Restless Legs Syndrome (RLS). The aim of this study is to compare the efficacy, tolerability,
      and safety of GEn at lower doses (450 and 300 mg/day) as well as the already approved dose of
      600 mg/day versus placebo for the treatment of subjects with moderate to severe primary RLS.
      This study is being conducted as a post-marketing commitment (PMC) as a condition of the
      approval of HORIZANT tablets (NDA 022399).
This is a Phase IV randomized, double-blind, placebo-controlled, fixed-dose, parallel group
      study to assess the efficacy, tolerability, and safety of 3 doses of GEn (600, 450, and 300
      mg/day) compared with placebo in the treatment of subjects with moderate-to-severe primary
      RLS.

      The study will include 9 visits over approximately 14 weeks for eligible subjects including a
      1-week Screening Period, a 12-week Treatment Period, and a 1 week Follow up Period. Screening
      will occur within 1 week of the first scheduled dose of study medication. The total duration
      of the study, from the first subject enrolled to the last subject completed will be
      approximately 2 years.

      Eligible subjects (at least 18 years of age) must have:

        -  a diagnosis of RLS according to the IRLSSG Diagnostic Criteria

        -  a history of RLS symptoms for at least 15 nights in the prior month or, if on treatment,
           this frequency of symptoms before treatment was started

        -  documented RLS symptoms for at least 4 of the 7 consecutive evenings/nights during the
           Screening Period, and a total RLS severity score of at least 15 on the International
           Restless Legs Syndrome (IRLS) Rating Scale at the screening and baseline visits

      Approximately 498 subjects will be enrolled, randomly assigned to treatment groups, and
      receive study medication once daily for 12 weeks. Subjects will be randomly assigned to
      receive 1 of the 4 following treatment groups in a ratio of 1:1:1:1:

        -  GEn 600 mg/day

        -  GEn 450 mg/day

        -  GEn 300 mg/day

        -  Matching placebo

      Subjects will be instructed to take their study medication once daily with food in the
      evening at approximately 5 PM. Each tablet must be swallowed whole and not divided, crushed,
      or chewed.

      Each subject, regardless of treatment assignment, will take 3 tablets of study medication (1
      tablet from Bottle A, 1 tablet from Bottle B, and 1 tablet from Bottle C) once daily
      continuing through the end of the Treatment Period (Week 12). Subjects will return to the
      study site for a follow-up visit (Visit 9, Week 13) approximately 1 week after the last dose
      of study medication.

      Each subject's participation in the study will be approximately 14 weeks unless they withdraw
      early from the study. For subjects who complete the study, Visit 9 (which can occur between
      Day 86 and 92) will be considered their end-of-study visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: The Change From Baseline to the End of Treatment in the International Restless Legs Syndrome (IRLS) Rating Scale Score
time frame: Baseline, 12 weeks
description: International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.
Change from Baseline = LOCF value at current visit - value at Baseline (the last nonmissing assessment before the first dose of study medication). A negative treatment difference indicates a benefit relative to placebo.
The change from baseline data is analyzed using an ANCOVA model with treatment and pooled site as the main effects and the baseline IRLS Rating Scale total score as a covariate.
measure: The Proportion of Subjects at the End of Treatment Who Are Responders With Either "Much Improved" or "Very Much Improved" on the Investigator-rated Clinical Global Impression of Improvement (CGI-I)
time frame: 12 weeks
description: Clinical Global Impression - Improvement Scale (CGI-I): 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), on the scale. Higher score = more affected. Number of subjects responding to treatment at Week 12 with respect to dose level. CGI-I Responders = subjects who reported CGI-I scores of very much improved or much improved.
measure: The Dose-response Relationship of Change From Baseline in IRLS Rating Scale Total Score at End of Treatment
time frame: Baseline, 12 Weeks
description: International Restless Legs Syndrome Rating Scale: Very severe=31-40, Severe=21-30, Moderate=11-20, Mild=1-10, None=0.
This model only includes treatment in the model. Least squares mean is used for analysis.
measure: The Dose-response Relationship for Investigator-rated CGI-I Scale at End of Treatment
time frame: 12 Weeks
arm group label: GSK1838262 600 mg
arm group type: Active Comparator
description: Once-daily dose with food in the evening at approximately 5 PM
arm group label: GSK1838262 450 mg
arm group type: Active Comparator
description: Once-daily dose with food in the evening at approximately 5 PM
arm group label: GSK1838262 300 mg
arm group type: Active Comparator
description: Once-daily dose with food in the evening at approximately 5 PM
arm group label: GSK1838262 placebo match
arm group type: Placebo Comparator
description: Once-daily dose with food in the evening at approximately 5 PM
intervention type: Drug
intervention name: GSK1838262 600 mg
description: Drug: GSK1838262 600 mg/day Comparison of 3 doses
arm group label: GSK1838262 600 mg
other name: Horizant
other name: gabapentin enacarbil GEn
other name: XP13512
intervention type: Drug
intervention name: GSK1838262 450 mg
description: Drug: GSK1838262 450 mg/day Comparison of 3 doses
arm group label: GSK1838262 450 mg
other name: Horizant
other name: gabapentin enacarbil GEn
other name: XP13512
intervention type: Drug
intervention name: GSK1838262 300 mg
description: Drug: GSK1838262 300 mg/day Comparison of 3 doses
arm group label: GSK1838262 300 mg
other name: Horizant
other name: gabapentin enacarbil GEn
other name: XP13512
intervention type: Drug
intervention name: GSK1838262 Placebo match
description: Drug; GSK1838262 placebo to match 600 mg, 450 mg, 300 mg doses
arm group label: GSK1838262 placebo match
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
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country: United States
responsible party type: Sponsor
mesh term: Psychomotor Agitation
mesh term: Restless Legs Syndrome
mesh term: Syndrome
mesh term: Gabapentin
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