<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/NCT01721317</url>
  </required_header>
  <id_info>
    <org_study_id>116878</org_study_id>
    <secondary_id>2012-003105-10</secondary_id>
    <nct_id>NCT01721317</nct_id>
  </id_info>
  <brief_title>Dose-Optimization, Adjunctive Treatment Study of Ezogabine/Retigabine Immediate Release in Partial-onset Seizures</brief_title>
  <official_title>Study PTG116878, a Dose-Optimization Study of Ezogabine/Retigabine Immediate Release Tablets Versus Placebo in the Adjunctive Treatment of Subjects With Partial-Onset Seizures</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bausch Health Americas, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase IV adjunctive treatment dose-optimization study evaluating the efficacy,&#xD;
      safety, and health outcomes of ezogabine/retigabine immediate release (IR) (GW582892)&#xD;
      compared with placebo in adult subjects with partial-onset seizures (POS). This randomized,&#xD;
      double-blind, placebo-controlled, parallel-group, multicenter study will compare&#xD;
      ezogabine/retigabine IR (investigator-selected daily doses of 600 milligram (mg)/day, 750&#xD;
      mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day) with placebo. Study drug will be taken three&#xD;
      times a day (TID) in equally or unequally divided doses.&#xD;
&#xD;
      The study design includes up to a 10-week (wk) Screening (≤2 wks)/Baseline (8 wks) Phase, a&#xD;
      Titration Phase (2 wks), Dose-Optimization Phase (8 wks), Maintenance Phase (8 wks), and&#xD;
      Taper/Follow-Up Phase (3 wks). The total duration of the study for each subject will be&#xD;
      approximately 31 wks, and at minimum approximately 27 wks if subjects provide reliable 28-day&#xD;
      retrospective seizure data.&#xD;
&#xD;
      Approximately 280 subjects will be screened with approximately 208 subjects randomly assigned&#xD;
      to 1 of 2 treatment groups in a 2:1 ratio (ezogabine/retigabine IR, or placebo).&#xD;
&#xD;
      Subjects will be instructed to start investigational product (IP) the day after the baseline&#xD;
      visit. During the first week of the Titration Phase, subjects will be taking 300 mg/day (100&#xD;
      mg TID). During the second week, subjects will be taking 450 mg/day (150 mg/day TID).&#xD;
&#xD;
      At the beginning of the Dose-Optimization Phase (3rd week of study drug) subjects will take&#xD;
      600 mg/day (200 mg TID) for one week. Thereafter during the Dose-Optimization Phase, subjects&#xD;
      will continue to increase their daily dose by 150 mg per week until they have achieved their&#xD;
      optimal tolerated dose. During this phase, the investigator may choose to have the subject&#xD;
      stay on his/her designated dose for another week before attempting a dose increase until&#xD;
      reaching a dose of 1200 mg/day. In addition, in the context of tolerability issues, the&#xD;
      subject may be reduced to the preceding dose level for one week before attempting to increase&#xD;
      the dose again at the next scheduled time point until the subject reaches optimal dose.&#xD;
      Subjects unable to tolerate a minimum of 600 mg/day will be discontinued from the study.&#xD;
&#xD;
      The Maintenance Phase will begin at Week 10 (Visit 8) and will last 8 weeks. During the&#xD;
      Maintenance Phase, subjects will remain on the daily TID dose achieved at the end of the&#xD;
      Dose-Optimization Phase.&#xD;
&#xD;
      Seizure type and frequency will be monitored throughout the study via a Seizure Calendar and&#xD;
      will be evaluated at each study visit. Subjects will be instructed to complete the daily&#xD;
      Seizure Calendar during each phase of the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    After reevaluation of the benefit: risk profile of ezogabine/retigabine, GSK does not believe&#xD;
    the early adjunctive treatment study population is appropriate.&#xD;
  </why_stopped>
  <start_date type="Actual">December 19, 2012</start_date>
  <completion_date type="Actual">June 20, 2013</completion_date>
  <primary_completion_date type="Actual">June 20, 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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Change in the 28-day Total Partial Seizure Frequency (POS) From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</measure>
    <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
    <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in the total partial seizure frequency, which was recorded by participants in the daily seizure calendar. The total 28-day POS rate is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percent Change in the 28-day Total Partial Seizure Frequency (POS) Within Each Stratum From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</measure>
    <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
    <description>The percent change in 28-day total POS frequency within each stratum (sodium channel blocker or non-sodium channel blocker) background antiepileptic drug (AED) was to be summarized as the supportive analysis. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percent Change in 28-day Total Partial Seizure Frequency (POS) for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</measure>
    <time_frame>Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
    <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in total partial seizure frequency during the Dose-Optimization Phase and Maintenance Phase. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Par. Experiencing &gt;=50% Reduction in 28-day Total Partial Seizure Frequency (POS) for the Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and Dose-Optimization + Maintenance Phase</measure>
    <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
    <description>Participants (par.) experiencing &gt;= 50% reduction from Baseline to the end of the Double-Blind Phase in 28-day total POS were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Seizure Free Participants for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</measure>
    <time_frame>Week 3 (start of Dose-Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
    <description>Participants without seizures during the interval of Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Number of Seizure Free Days for the Indicated Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and the Dose-Optimization + Maintenance Phase</measure>
    <time_frame>Week 0 (end of Baseline Phase) to Week 18 (end of Maintenance Phase)</time_frame>
    <description>The change in number of seizure free days during the Double-Blind period, the Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Functional Status (Epilepsy-related Worry and Activity Limitation) and Productivity (Missed Work or School) to the End of the Dose-Optimization Phase and the End of the Maintenance Phase</measure>
    <time_frame>Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
    <description>The effect of ezogabine/retigabine IR as an adjunctive treatment on health outcomes was to be evaluated on the basis of functional status and productivity. Participants were asked to complete the paper functional status diary to collect information to assess how the participant's functional status is affected by their epilepsy symptoms. Participants were asked to rate their epilepsy-related worry, activity limitations, and productivity (missed work or school). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of New Seizure Types in Participants Without a History of These Seizure Types</measure>
    <time_frame>Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)</time_frame>
    <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of new seizure types in participants without a history of these seizure types. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants at Each Dose During the Maintenance Phase and Average Maintenance Dose Over All Participants</measure>
    <time_frame>Week 11 (start of Maintenance Phase) to Week 18 (end of Maintenance Phase)</time_frame>
    <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the number of participants at each dose during the Maintenance Phase and the average maintenance dose over all participants. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Early Study Discontinuation</measure>
    <time_frame>Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)</time_frame>
    <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of participants with early study discontinuation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Body Weight</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>Change from Baseline in body weight was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>Change from Baseline in blood pressure was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Heart Rate</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>Change from Baseline in heart rate was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>Change from Baseline in the QT interval using Bazett's correction (QTcB) and QT interval using Fridericia's correction were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils and Red Blood Cell (RBC) Distribution Width</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils, White Blood Cell (WBC) Count and Platelet Count</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Hematocrit</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Red Blood Cell (RBC) Count</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Mean Corpuscle Hemoglobin</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Albumin and Total Protein</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyltransferase (GGT)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid and Creatinine</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Calcium, Chloride, Potassium, Sodium, Glucose, Magnesium, Phosphorus Inorganic, Bicarbonate and Urea/Blood Urea Nitrogen (BUN)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in BUN/Creatinine Ratio</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry tests was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Creatinine Clearance</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated chemistry test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Urine Specific Gravity (USG)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Urine Potential of Hydrogen (pH)</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize ot evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick</measure>
    <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
    <description>The change from Baseline in the following urinalysis parameters (urine occult blood, urine glucose, urine ketones and urine protein) were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Post-void Residual (PVR) Urinary Bladder Ultrasound Volume</measure>
    <time_frame>Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase) and Week 18 (end of Maintenance Phase)</time_frame>
    <description>The change from Baseline in the PVR bladder ultrasound results was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With the Indicated Assessment Events of Suicidal Behavior, Suicidal Ideation or Non-suicidal Self Injurious Behavior Via the Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 4, Week 6 and Week 8</time_frame>
    <description>Prospective assessment of suicidality was conducted using the Columbia-Suicide Severity Rating Scale (C-SSRS), a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. C-SSRS data were only collected through Week 8 for the 6 randomized participants. Due to the study being prematurely terminated, there was not sufficient data to evaluate this endpoint.</description>
  </secondary_outcome>
  <number_of_arms>16</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Seizures</condition>
  <arm_group>
    <arm_group_label>Titration Phase: Ezogabine/Retigabine 300 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 300 mg equally divided TID over Wk 1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Titration Phase: Placebo 300 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Titration Phase: Ezogabine/Retigabine 450 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 450 mg equally divided TID over Wk 2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Titration Phase: Placebo 450 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 600 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 600 mg equally divided (200 mg TID) over Wk 3 or until they achieve their optimal tolerated dose as assessed by the Investigator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Placebo 600 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 750 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 750 mg equally or unequally divided TID over Wk 4 or until they achieve their optimal tolerated dose as assessed by the Investigator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Placebo 750 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 900 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 900 mg equally or unequally divided TID over Wk 5 or until they achieve their optimal tolerated dose as assessed by the Investigator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Placebo 900 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 1050 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 1050 mg equally or unequally divided TID over Wk 6 or until they achieve their optimal tolerated dose as assessed by the Investigator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Placebo 1050 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 1200 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine 1200 mg equally divided (400 mg TID) over Wk 7 or until they achieve their optimal tolerated dose as assessed by the Investigator</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose-Optimization Phase: Placebo 1200 mg</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance Phase:Ezogabine/Retigabine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects receive Ezogabine/Retigabine at the daily dose achieved (equally or unequally divided TID) at the end of the Dose-Optimization Phase for 8 Weeks (600 mg, 750 mg, 900 mg, 1050 mg, or 1200 mg)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance Phase: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects receive matching Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ezogabine/Retigabine IR</intervention_name>
    <description>Subjects received drug (dose strength 300 mg to 1200 mg) orally with or without food. The 3 daily doses are to be administered with approximately an 8-hour interval between them.</description>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 1050 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 1200 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 600 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 750 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Ezogabine/Retigabine 900 mg</arm_group_label>
    <arm_group_label>Maintenance Phase:Ezogabine/Retigabine</arm_group_label>
    <arm_group_label>Titration Phase: Ezogabine/Retigabine 300 mg</arm_group_label>
    <arm_group_label>Titration Phase: Ezogabine/Retigabine 450 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo will be available</description>
    <arm_group_label>Dose-Optimization Phase: Placebo 1050 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Placebo 1200 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Placebo 600 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Placebo 750 mg</arm_group_label>
    <arm_group_label>Dose-Optimization Phase: Placebo 900 mg</arm_group_label>
    <arm_group_label>Maintenance Phase: Placebo</arm_group_label>
    <arm_group_label>Titration Phase: Placebo 300 mg</arm_group_label>
    <arm_group_label>Titration Phase: Placebo 450 mg</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A male or female of 18 years of age or above capable of giving written informed&#xD;
             consent&#xD;
&#xD;
          -  Have a confident diagnosis of epilepsy for &gt;=6 months with partial-onset seizures&#xD;
             (POS), i.e., simple or complex POS with or without secondary generalization&#xD;
             (classified according to the International League Against Epilepsy (ILAE) Guidelines,&#xD;
             prior to the Screening Visit&#xD;
&#xD;
          -  Currently receiving monotherapy treatment with an antiepileptic drug (AED) at a stable&#xD;
             dose for at least 28 days prior to the screening visit (Visit 1). If the subject is&#xD;
             taking a barbiturate (e.g., phenobarbital), the dose must be stable for ≥3 months&#xD;
             prior to the Screening Visit. Note: Subjects who have received previous adjunctive&#xD;
             treatment but are currently taking one AED are eligible for enrolment.&#xD;
&#xD;
          -  Investigator-confirmed partial seizure frequency rate of ≥3 partial seizures per 28&#xD;
             days over the 8 weeks preceding the screening visit and must not have been&#xD;
             seizure-free for ≥ 21 consecutive days.&#xD;
&#xD;
          -  Female of non-child bearing potential, or female of child-bearing potential willing to&#xD;
             use protocol-specified methods of contraception to prevent pregnancy during the study.&#xD;
&#xD;
          -  Capable to comply with dosing of study drug, background AED, all study procedures and&#xD;
             to maintain an accurate and complete daily written Seizure Calendar and Functional&#xD;
             Status Diary&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have generalized epilepsy (e.g. Lennox-Gastaut, Juvenile Myoclonic epilepsy, Absence,&#xD;
             etc.) or non-epileptic seizures.&#xD;
&#xD;
          -  Have had innumerable seizures within the 12-month period prior to the Screening Visit&#xD;
             where the individual seizures cannot be counted.&#xD;
&#xD;
          -  Have had status epilepticus within 12 months prior to screening&#xD;
&#xD;
          -  Have a history of pseudo seizures, non-epileptic events or any other type of&#xD;
             psychogenic seizures that could be confused with seizures.&#xD;
&#xD;
          -  Have been treated with felbamate or vigabatrin within the 6 months prior to Screening.&#xD;
             If a subject has been previously treated with vigabatrin &gt;6 months prior to Screening,&#xD;
             a visual perimetry test performed within 6 months prior to Screening must show normal&#xD;
             visual fields or no worsening of recognized visual field abnormalities as compared&#xD;
             with prior to vigabatrin treatment&#xD;
&#xD;
          -  Benzodiazepines used in any manner other than acute usage as defined in this protocol&#xD;
             will be considered concurrent AED usage and will not be permitted&#xD;
&#xD;
               -  Are using Central Nervous System (CNS)-active medication (other than concomitant&#xD;
                  AED therapy), unless the subject has been stabilized on such medication for at&#xD;
                  least 1 month prior to the Screening Visit.&#xD;
&#xD;
          -  Are using herbal treatments with CNS activity within at least 1 month prior to the&#xD;
             Screening Visit&#xD;
&#xD;
          -  Have received ezogabine/retigabine in a previous study or have taken POTIGA or&#xD;
             TROBALT.&#xD;
&#xD;
          -  Are currently following or planning to follow the ketogenic diet&#xD;
&#xD;
          -  Have an active Vagus Nerve Stimulator (VNS) to control seizures&#xD;
&#xD;
          -  Are planning surgery to control seizures during the study&#xD;
&#xD;
          -  Have impaired renal function as judged by a creatinine clearance of &lt;50 mL/min&#xD;
&#xD;
          -  Have a history of urinary retention or risk factors for urinary retention that in the&#xD;
             investigator's judgment could potentially affect subject safety.&#xD;
&#xD;
          -  Have an average corrected QT interval (QTc), using Bazett's QT correction (QTcB),&#xD;
             ≥450msec or ≥480msec for subjects with bundle branch block at the time of the&#xD;
             Screening Visit&#xD;
&#xD;
          -  Liver function tests: alanine aminotransferase (ALT) is ≥2 times the upper limit of&#xD;
             normal (ULN); alkaline phosphatase and bilirubin are &gt;1.5 × ULN (isolated bilirubin&#xD;
             &gt;1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin is &lt;35%).&#xD;
&#xD;
          -  Are suffering from acute or progressive neurological disease, severe psychiatric&#xD;
             disease, or severe mental abnormalities that are likely to interfere with the&#xD;
             objectives of the study&#xD;
&#xD;
          -  Have a history of malignancy within the past 2 years; with the exception of basal cell&#xD;
             carcinoma&#xD;
&#xD;
          -  Have unstable liver disease [chronic stable hepatitis B and C are acceptable if&#xD;
             subject otherwise meets entry criteria; chronic stable Hepatitis B to be excluded if&#xD;
             significant immunosuppressive agents administered due to risk of hepatitis B&#xD;
             reactivation]&#xD;
&#xD;
          -  Have any medical condition that, in the investigator's judgment, is considered to be&#xD;
             clinically significant and could potentially affect subject safety or study outcome,&#xD;
             including but not limited to: clinically significant cardiac, renal, hepatic&#xD;
             condition, or a condition that affects the absorption, distribution, metabolism or&#xD;
             excretion of drugs&#xD;
&#xD;
          -  Have an active suicidal plan/intent or have had active suicidal thoughts in the past 6&#xD;
             months. Have history of suicide attempt in the last 2 years or more than 1 lifetime&#xD;
             suicide attempt.&#xD;
&#xD;
          -  Have a history of substance abuse (alcohol or drugs) or substance dependence within 12&#xD;
             months prior to screening&#xD;
&#xD;
          -  Have a known hypersensitivity to any components of the study medication&#xD;
&#xD;
          -  Have taken an investigational drug, or used an investigational device, within the&#xD;
             previous 30 days prior to screening or plans to take an investigational drug anytime&#xD;
             during the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</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>Fresno</city>
        <state>California</state>
        <zip>93710</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>Port Charlotte</city>
        <state>Florida</state>
        <zip>33952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Bethesda</city>
        <state>Maryland</state>
        <zip>20817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Golden Valley</city>
        <state>Minnesota</state>
        <zip>55422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <zip>97504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <zip>76017</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Kingwood</city>
        <state>Texas</state>
        <zip>77339</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Athens</city>
        <zip>10676</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Thessaloniki</city>
        <zip>57010</zip>
        <country>Greece</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Greece</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Poland</country>
  </removed_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>November 1, 2012</study_first_submitted>
  <study_first_submitted_qc>November 1, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 4, 2012</study_first_posted>
  <results_first_submitted>February 6, 2014</results_first_submitted>
  <results_first_submitted_qc>February 6, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">March 26, 2014</results_first_posted>
  <last_update_submitted>December 2, 2020</last_update_submitted>
  <last_update_submitted_qc>December 2, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Ezogabine/Retigabine</keyword>
  <keyword>Adjunctive Treatment</keyword>
  <keyword>Safety</keyword>
  <keyword>Efficacy</keyword>
  <keyword>Epilepsy</keyword>
  <keyword>Tolerability</keyword>
  <keyword>Immediate Release</keyword>
  <keyword>GW582892</keyword>
  <keyword>Dose-Optimization</keyword>
  <keyword>Partial-Onset Seizures</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Seizures</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ezogabine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter study comparing ezogabine/retigabine immediate release (IR) with placebo, as adjunctive treatment in adults with partial-onset seizures. The study was prematurely discontinued after randomizing only 6 of the planned 208 participants.</recruitment_details>
      <pre_assignment_details>The study consisted of a 2-week (or less) Screening Phase, an 8-week Baseline Phase, a 2-week Titration Phase, an 8-week Dose-Optimization Phase, an 8-week Maintenance Phase, and a 3-week Taper Phase.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received matching ezogabine/retigabine IR placebo orally three times a day (TID) in equally or unequally divided doses.</description>
        </group>
        <group group_id="P2">
          <title>Ezogabine/Retigabine IR</title>
          <description>Participants received investigator-selected daily doses of 600 milligrams (mg)/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Closed / Terminated</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
        </group>
        <group group_id="B2">
          <title>Ezogabine/Retigabine IR</title>
          <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
            <count group_id="B2" value="4"/>
            <count group_id="B3" value="6"/>
          </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="42.5" spread="10.61"/>
                    <measurement group_id="B2" value="42.8" spread="16.32"/>
                    <measurement group_id="B3" value="42.7" spread="13.50"/>
                  </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="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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>White - White/Caucasian/European</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in the 28-day Total Partial Seizure Frequency (POS) From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</title>
        <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in the total partial seizure frequency, which was recorded by participants in the daily seizure calendar. The total 28-day POS rate is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
        <population>Intent-to-Treat (ITT) Population: all randomized participants who received &gt;= 1 dose of study medication and who had &gt;= 1 post-Baseline seizure diary day with &gt;= 0 seizures recorded.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the 28-day Total Partial Seizure Frequency (POS) From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</title>
          <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in the total partial seizure frequency, which was recorded by participants in the daily seizure calendar. The total 28-day POS rate is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Intent-to-Treat (ITT) Population: all randomized participants who received &gt;= 1 dose of study medication and who had &gt;= 1 post-Baseline seizure diary day with &gt;= 0 seizures recorded.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percent Change in the 28-day Total Partial Seizure Frequency (POS) Within Each Stratum From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</title>
        <description>The percent change in 28-day total POS frequency within each stratum (sodium channel blocker or non-sodium channel blocker) background antiepileptic drug (AED) was to be summarized as the supportive analysis. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in the 28-day Total Partial Seizure Frequency (POS) Within Each Stratum From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)</title>
          <description>The percent change in 28-day total POS frequency within each stratum (sodium channel blocker or non-sodium channel blocker) background antiepileptic drug (AED) was to be summarized as the supportive analysis. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change in 28-day Total Partial Seizure Frequency (POS) for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</title>
        <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in total partial seizure frequency during the Dose-Optimization Phase and Maintenance Phase. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change in 28-day Total Partial Seizure Frequency (POS) for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</title>
          <description>The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in total partial seizure frequency during the Dose-Optimization Phase and Maintenance Phase. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or &gt; 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Par. Experiencing &gt;=50% Reduction in 28-day Total Partial Seizure Frequency (POS) for the Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and Dose-Optimization + Maintenance Phase</title>
        <description>Participants (par.) experiencing &gt;= 50% reduction from Baseline to the end of the Double-Blind Phase in 28-day total POS were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Par. Experiencing &gt;=50% Reduction in 28-day Total Partial Seizure Frequency (POS) for the Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and Dose-Optimization + Maintenance Phase</title>
          <description>Participants (par.) experiencing &gt;= 50% reduction from Baseline to the end of the Double-Blind Phase in 28-day total POS were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Seizure Free Participants for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</title>
        <description>Participants without seizures during the interval of Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 3 (start of Dose-Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Seizure Free Participants for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase</title>
          <description>Participants without seizures during the interval of Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Number of Seizure Free Days for the Indicated Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and the Dose-Optimization + Maintenance Phase</title>
        <description>The change in number of seizure free days during the Double-Blind period, the Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase) to Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Number of Seizure Free Days for the Indicated Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and the Dose-Optimization + Maintenance Phase</title>
          <description>The change in number of seizure free days during the Double-Blind period, the Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Functional Status (Epilepsy-related Worry and Activity Limitation) and Productivity (Missed Work or School) to the End of the Dose-Optimization Phase and the End of the Maintenance Phase</title>
        <description>The effect of ezogabine/retigabine IR as an adjunctive treatment on health outcomes was to be evaluated on the basis of functional status and productivity. Participants were asked to complete the paper functional status diary to collect information to assess how the participant's functional status is affected by their epilepsy symptoms. Participants were asked to rate their epilepsy-related worry, activity limitations, and productivity (missed work or school). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)</time_frame>
        <population>ITT Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Functional Status (Epilepsy-related Worry and Activity Limitation) and Productivity (Missed Work or School) to the End of the Dose-Optimization Phase and the End of the Maintenance Phase</title>
          <description>The effect of ezogabine/retigabine IR as an adjunctive treatment on health outcomes was to be evaluated on the basis of functional status and productivity. Participants were asked to complete the paper functional status diary to collect information to assess how the participant's functional status is affected by their epilepsy symptoms. Participants were asked to rate their epilepsy-related worry, activity limitations, and productivity (missed work or school). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>ITT Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Incidence of New Seizure Types in Participants Without a History of These Seizure Types</title>
        <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of new seizure types in participants without a history of these seizure types. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population: all randomized participants who receive &gt;= 1 dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Incidence of New Seizure Types in Participants Without a History of These Seizure Types</title>
          <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of new seizure types in participants without a history of these seizure types. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population: all randomized participants who receive &gt;= 1 dose of study medication.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants at Each Dose During the Maintenance Phase and Average Maintenance Dose Over All Participants</title>
        <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the number of participants at each dose during the Maintenance Phase and the average maintenance dose over all participants. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 11 (start of Maintenance Phase) to Week 18 (end of Maintenance Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants at Each Dose During the Maintenance Phase and Average Maintenance Dose Over All Participants</title>
          <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the number of participants at each dose during the Maintenance Phase and the average maintenance dose over all participants. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Early Study Discontinuation</title>
        <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of participants with early study discontinuation.</description>
        <time_frame>Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Early Study Discontinuation</title>
          <description>The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of participants with early study discontinuation.</description>
          <population>Safety Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Body Weight</title>
        <description>Change from Baseline in body weight was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Body Weight</title>
          <description>Change from Baseline in body weight was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</title>
        <description>Change from Baseline in blood pressure was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)</title>
          <description>Change from Baseline in blood pressure was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Heart Rate</title>
        <description>Change from Baseline in heart rate was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Heart Rate</title>
          <description>Change from Baseline in heart rate was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)</title>
        <description>Change from Baseline in the QT interval using Bazett's correction (QTcB) and QT interval using Fridericia's correction were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)</title>
          <description>Change from Baseline in the QT interval using Bazett's correction (QTcB) and QT interval using Fridericia's correction were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils and Red Blood Cell (RBC) Distribution Width</title>
        <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils and Red Blood Cell (RBC) Distribution Width</title>
          <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils, White Blood Cell (WBC) Count and Platelet Count</title>
        <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils, White Blood Cell (WBC) Count and Platelet Count</title>
          <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration</title>
        <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration</title>
          <description>The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Hematocrit</title>
        <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Hematocrit</title>
          <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Red Blood Cell (RBC) Count</title>
        <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Red Blood Cell (RBC) Count</title>
          <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Mean Corpuscle Hemoglobin</title>
        <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Mean Corpuscle Hemoglobin</title>
          <description>The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Albumin and Total Protein</title>
        <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Albumin and Total Protein</title>
          <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyltransferase (GGT)</title>
        <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyltransferase (GGT)</title>
          <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid and Creatinine</title>
        <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid and Creatinine</title>
          <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Calcium, Chloride, Potassium, Sodium, Glucose, Magnesium, Phosphorus Inorganic, Bicarbonate and Urea/Blood Urea Nitrogen (BUN)</title>
        <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Calcium, Chloride, Potassium, Sodium, Glucose, Magnesium, Phosphorus Inorganic, Bicarbonate and Urea/Blood Urea Nitrogen (BUN)</title>
          <description>The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in BUN/Creatinine Ratio</title>
        <description>The change from Baseline in the indicated chemistry tests was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in BUN/Creatinine Ratio</title>
          <description>The change from Baseline in the indicated chemistry tests was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Creatinine Clearance</title>
        <description>The change from Baseline in the indicated chemistry test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Creatinine Clearance</title>
          <description>The change from Baseline in the indicated chemistry test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Urine Specific Gravity (USG)</title>
        <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Urine Specific Gravity (USG)</title>
          <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Urine Potential of Hydrogen (pH)</title>
        <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize ot evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Urine Potential of Hydrogen (pH)</title>
          <description>The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize ot evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick</title>
        <description>The change from Baseline in the following urinalysis parameters (urine occult blood, urine glucose, urine ketones and urine protein) were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick</title>
          <description>The change from Baseline in the following urinalysis parameters (urine occult blood, urine glucose, urine ketones and urine protein) were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Post-void Residual (PVR) Urinary Bladder Ultrasound Volume</title>
        <description>The change from Baseline in the PVR bladder ultrasound results was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase) and Week 18 (end of Maintenance Phase)</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Post-void Residual (PVR) Urinary Bladder Ultrasound Volume</title>
          <description>The change from Baseline in the PVR bladder ultrasound results was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.</description>
          <population>Safety Population</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With the Indicated Assessment Events of Suicidal Behavior, Suicidal Ideation or Non-suicidal Self Injurious Behavior Via the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
        <description>Prospective assessment of suicidality was conducted using the Columbia-Suicide Severity Rating Scale (C-SSRS), a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. C-SSRS data were only collected through Week 8 for the 6 randomized participants. Due to the study being prematurely terminated, there was not sufficient data to evaluate this endpoint.</description>
        <time_frame>Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 4, Week 6 and Week 8</time_frame>
        <population>Safety Population</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
          </group>
          <group group_id="O2">
            <title>Ezogabine/Retigabine IR</title>
            <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With the Indicated Assessment Events of Suicidal Behavior, Suicidal Ideation or Non-suicidal Self Injurious Behavior Via the Columbia Suicide Severity Rating Scale (C-SSRS)</title>
          <description>Prospective assessment of suicidality was conducted using the Columbia-Suicide Severity Rating Scale (C-SSRS), a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. C-SSRS data were only collected through Week 8 for the 6 randomized participants. Due to the study being prematurely terminated, there was not sufficient data to evaluate this endpoint.</description>
          <population>Safety Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
                <count group_id="O2" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the investigational product until the Follow-up period (up to Study Day 147).</time_frame>
      <desc>SAEs and non-serious AEs are reported for members of the Safety Population, comprised of all participants who received at least one dose of study treatment.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received matching ezogabine/retigabine IR placebo orally TID in equally or unequally divided doses.</description>
        </group>
        <group group_id="E2">
          <title>Ezogabine/Retigabine IR</title>
          <description>Participants received investigator-selected daily doses of 600 mg/day, 750 mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day of ezogabine/retigabine IR. The study drug was taken orally TID in equally or unequally divided doses.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="4"/>
              </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>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</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/NCT01721317
org study id: 116878
secondary id: 2012-003105-10
nct id: NCT01721317
lead sponsor: 
collaborator: 
has dmc: No
This is a Phase IV adjunctive treatment dose-optimization study evaluating the efficacy,
      safety, and health outcomes of ezogabine/retigabine immediate release (IR) (GW582892)
      compared with placebo in adult subjects with partial-onset seizures (POS). This randomized,
      double-blind, placebo-controlled, parallel-group, multicenter study will compare
      ezogabine/retigabine IR (investigator-selected daily doses of 600 milligram (mg)/day, 750
      mg/day, 900 mg/day, 1050 mg/day or 1200 mg/day) with placebo. Study drug will be taken three
      times a day (TID) in equally or unequally divided doses.

      The study design includes up to a 10-week (wk) Screening (≤2 wks)/Baseline (8 wks) Phase, a
      Titration Phase (2 wks), Dose-Optimization Phase (8 wks), Maintenance Phase (8 wks), and
      Taper/Follow-Up Phase (3 wks). The total duration of the study for each subject will be
      approximately 31 wks, and at minimum approximately 27 wks if subjects provide reliable 28-day
      retrospective seizure data.

      Approximately 280 subjects will be screened with approximately 208 subjects randomly assigned
      to 1 of 2 treatment groups in a 2:1 ratio (ezogabine/retigabine IR, or placebo).

      Subjects will be instructed to start investigational product (IP) the day after the baseline
      visit. During the first week of the Titration Phase, subjects will be taking 300 mg/day (100
      mg TID). During the second week, subjects will be taking 450 mg/day (150 mg/day TID).

      At the beginning of the Dose-Optimization Phase (3rd week of study drug) subjects will take
      600 mg/day (200 mg TID) for one week. Thereafter during the Dose-Optimization Phase, subjects
      will continue to increase their daily dose by 150 mg per week until they have achieved their
      optimal tolerated dose. During this phase, the investigator may choose to have the subject
      stay on his/her designated dose for another week before attempting a dose increase until
      reaching a dose of 1200 mg/day. In addition, in the context of tolerability issues, the
      subject may be reduced to the preceding dose level for one week before attempting to increase
      the dose again at the next scheduled time point until the subject reaches optimal dose.
      Subjects unable to tolerate a minimum of 600 mg/day will be discontinued from the study.

      The Maintenance Phase will begin at Week 10 (Visit 8) and will last 8 weeks. During the
      Maintenance Phase, subjects will remain on the daily TID dose achieved at the end of the
      Dose-Optimization Phase.

      Seizure type and frequency will be monitored throughout the study via a Seizure Calendar and
      will be evaluated at each study visit. Subjects will be instructed to complete the daily
      Seizure Calendar during each phase of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percent Change in the 28-day Total Partial Seizure Frequency (POS) From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)
time frame: Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)
description: The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in the total partial seizure frequency, which was recorded by participants in the daily seizure calendar. The total 28-day POS rate is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or > 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Percent Change in the 28-day Total Partial Seizure Frequency (POS) Within Each Stratum From Week 0 (End of Baseline Phase) Through Week 18 (End of Maintenance Phase)
time frame: Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)
description: The percent change in 28-day total POS frequency within each stratum (sodium channel blocker or non-sodium channel blocker) background antiepileptic drug (AED) was to be summarized as the supportive analysis. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or > 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Percent Change in 28-day Total Partial Seizure Frequency (POS) for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase
time frame: Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)
description: The efficacy of ezogabine/retigabine IR as an adjunctive treatment was to be evaluated by the percent change in total partial seizure frequency during the Dose-Optimization Phase and Maintenance Phase. The total 28-day POS value is defined as the total number of POS reported during the evaluation period divided by the total number of applicable days during the evaluation period with this quotient multiplied by 28 days. The applicable days are the days in which the participant had non-missing seizure data (i.e., either 0 or > 0 seizures recorded). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Number of Par. Experiencing >=50% Reduction in 28-day Total Partial Seizure Frequency (POS) for the Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and Dose-Optimization + Maintenance Phase
time frame: Week 0 (end of Baseline Phase) through Week 18 (end of Maintenance Phase)
description: Participants (par.) experiencing >= 50% reduction from Baseline to the end of the Double-Blind Phase in 28-day total POS were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Number of Seizure Free Participants for the Indicated Intervals: Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase
time frame: Week 3 (start of Dose-Optimization Phase) to Week 18 (end of Maintenance Phase)
description: Participants without seizures during the interval of Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in the Number of Seizure Free Days for the Indicated Intervals: Double-blind Period (Titration Phase + Dose-Optimization Phase + Maintenance Phase), Maintenance Phase and the Dose-Optimization + Maintenance Phase
time frame: Week 0 (end of Baseline Phase) to Week 18 (end of Maintenance Phase)
description: The change in number of seizure free days during the Double-Blind period, the Maintenance Phase and the Dose-Optimization Phase + Maintenance Phase were to be reported. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Percent Change From Baseline in Functional Status (Epilepsy-related Worry and Activity Limitation) and Productivity (Missed Work or School) to the End of the Dose-Optimization Phase and the End of the Maintenance Phase
time frame: Week 3 (start of Dose -Optimization Phase) to Week 18 (end of Maintenance Phase)
description: The effect of ezogabine/retigabine IR as an adjunctive treatment on health outcomes was to be evaluated on the basis of functional status and productivity. Participants were asked to complete the paper functional status diary to collect information to assess how the participant's functional status is affected by their epilepsy symptoms. Participants were asked to rate their epilepsy-related worry, activity limitations, and productivity (missed work or school). Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Incidence of New Seizure Types in Participants Without a History of These Seizure Types
time frame: Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)
description: The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of new seizure types in participants without a history of these seizure types. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Number of Participants at Each Dose During the Maintenance Phase and Average Maintenance Dose Over All Participants
time frame: Week 11 (start of Maintenance Phase) to Week 18 (end of Maintenance Phase)
description: The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the number of participants at each dose during the Maintenance Phase and the average maintenance dose over all participants. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Number of Participants With Early Study Discontinuation
time frame: Week 0 (end of Baseline Phase) to Week 21 (end of Taper Phase)
description: The safety and tolerability of ezogabine/retigabine IR was to be evaluated by recording the incidence of participants with early study discontinuation.
measure: Change From Baseline in Body Weight
time frame: Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: Change from Baseline in body weight was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)
time frame: Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: Change from Baseline in blood pressure was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Heart Rate
time frame: Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: Change from Baseline in heart rate was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)
time frame: Screening, Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: Change from Baseline in the QT interval using Bazett's correction (QTcB) and QT interval using Fridericia's correction were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in the Percentage of Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils and Red Blood Cell (RBC) Distribution Width
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in the Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Segmented Neutrophils, White Blood Cell (WBC) Count and Platelet Count
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Hemoglobin and Mean Corpuscle Hemoglobin Concentration
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Hematocrit
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Red Blood Cell (RBC) Count
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Mean Corpuscle Hemoglobin
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated hematology test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Albumin and Total Protein
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase, Lactate Dehydrogenase and Gamma Glutamyltransferase (GGT)
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Uric Acid and Creatinine
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Calcium, Chloride, Potassium, Sodium, Glucose, Magnesium, Phosphorus Inorganic, Bicarbonate and Urea/Blood Urea Nitrogen (BUN)
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry tests were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in BUN/Creatinine Ratio
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry tests was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Creatinine Clearance
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated chemistry test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Urine Specific Gravity (USG)
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Urine Potential of Hydrogen (pH)
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the indicated urinalysis test was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize ot evaluate this endpoint.
measure: Number of Participants for the Indicated Urinalysis Parameters Tested by Dipstick
time frame: Screening, Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase), Week 18 (end of Maintenance Phase) and Week 21 (end of Taper Phase)
description: The change from Baseline in the following urinalysis parameters (urine occult blood, urine glucose, urine ketones and urine protein) were to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Change From Baseline in Post-void Residual (PVR) Urinary Bladder Ultrasound Volume
time frame: Week 0 (end of Baseline Phase), Week 10 (end of Dose-Optimization Phase) and Week 18 (end of Maintenance Phase)
description: The change from Baseline in the PVR bladder ultrasound results was to be assessed. Due to the study being prematurely terminated, there was not sufficient data to summarize or evaluate this endpoint.
measure: Number of Participants With the Indicated Assessment Events of Suicidal Behavior, Suicidal Ideation or Non-suicidal Self Injurious Behavior Via the Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: Week 0 (end of Baseline Phase), Week 2 (end of Titration Phase), Week 4, Week 6 and Week 8
description: Prospective assessment of suicidality was conducted using the Columbia-Suicide Severity Rating Scale (C-SSRS), a brief questionnaire designed to assess severity and change in suicidality by integrating both behavior and ideation using a semi-structured interview to probe participant responses. C-SSRS data were only collected through Week 8 for the 6 randomized participants. Due to the study being prematurely terminated, there was not sufficient data to evaluate this endpoint.
arm group label: Titration Phase: Ezogabine/Retigabine 300 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 300 mg equally divided TID over Wk 1
arm group label: Titration Phase: Placebo 300 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Titration Phase: Ezogabine/Retigabine 450 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 450 mg equally divided TID over Wk 2
arm group label: Titration Phase: Placebo 450 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 600 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 600 mg equally divided (200 mg TID) over Wk 3 or until they achieve their optimal tolerated dose as assessed by the Investigator
arm group label: Dose-Optimization Phase: Placebo 600 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 750 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 750 mg equally or unequally divided TID over Wk 4 or until they achieve their optimal tolerated dose as assessed by the Investigator
arm group label: Dose-Optimization Phase: Placebo 750 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 900 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 900 mg equally or unequally divided TID over Wk 5 or until they achieve their optimal tolerated dose as assessed by the Investigator
arm group label: Dose-Optimization Phase: Placebo 900 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 1050 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 1050 mg equally or unequally divided TID over Wk 6 or until they achieve their optimal tolerated dose as assessed by the Investigator
arm group label: Dose-Optimization Phase: Placebo 1050 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 1200 mg
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine 1200 mg equally divided (400 mg TID) over Wk 7 or until they achieve their optimal tolerated dose as assessed by the Investigator
arm group label: Dose-Optimization Phase: Placebo 1200 mg
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
arm group label: Maintenance Phase:Ezogabine/Retigabine
arm group type: Experimental
description: Subjects receive Ezogabine/Retigabine at the daily dose achieved (equally or unequally divided TID) at the end of the Dose-Optimization Phase for 8 Weeks (600 mg, 750 mg, 900 mg, 1050 mg, or 1200 mg)
arm group label: Maintenance Phase: Placebo
arm group type: Placebo Comparator
description: Subjects receive matching Placebo
intervention type: Drug
intervention name: Ezogabine/Retigabine IR
description: Subjects received drug (dose strength 300 mg to 1200 mg) orally with or without food. The 3 daily doses are to be administered with approximately an 8-hour interval between them.
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 1050 mg
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 1200 mg
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 600 mg
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 750 mg
arm group label: Dose-Optimization Phase: Ezogabine/Retigabine 900 mg
arm group label: Maintenance Phase:Ezogabine/Retigabine
arm group label: Titration Phase: Ezogabine/Retigabine 300 mg
arm group label: Titration Phase: Ezogabine/Retigabine 450 mg
intervention type: Drug
intervention name: Placebo
description: Matching placebo will be available
arm group label: Dose-Optimization Phase: Placebo 1050 mg
arm group label: Dose-Optimization Phase: Placebo 1200 mg
arm group label: Dose-Optimization Phase: Placebo 600 mg
arm group label: Dose-Optimization Phase: Placebo 750 mg
arm group label: Dose-Optimization Phase: Placebo 900 mg
arm group label: Maintenance Phase: Placebo
arm group label: Titration Phase: Placebo 300 mg
arm group label: Titration Phase: Placebo 450 mg
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Greece
country: United States
country: Poland
responsible party type: Sponsor
mesh term: Seizures
mesh term: Ezogabine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 