<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/NCT01691872</url>
  </required_header>
  <id_info>
    <org_study_id>116247</org_study_id>
    <nct_id>NCT01691872</nct_id>
  </id_info>
  <brief_title>Pharmacokinetic Study of Retigabine Extended Release (XR) Formulation in Healthy Adult Japanese and Caucasian Subjects</brief_title>
  <official_title>An Open-label, Single Centre, Parallel Group Study to Evaluate the Safety and Pharmacokinetics of Single Oral Doses of Retigabine Extended Release (XR) Formulation in Healthy Adult Japanese and Caucasian Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is an open-label, single centre, parallel group study to evaluate the safety and&#xD;
      pharmacokinetics of single oral doses of retigabine XR formulation in healthy adult Japanese&#xD;
      subjects. To compare the pharmacokinetic and safety profile, Caucasian subjects are also&#xD;
      incorporated. This study is intended to facilitate inclusion of Japanese patients in the&#xD;
      global phase III program for retigabine XR formulation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Development plan of retigabine XR in Japan was readjusted.&#xD;
  </why_stopped>
  <start_date type="Actual">October 10, 2012</start_date>
  <completion_date type="Actual">October 18, 2012</completion_date>
  <primary_completion_date type="Actual">October 18, 2012</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-∞ of retigabine</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of retigabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of retigabine</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Maximum observed concentration of retigabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax of retigabine</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Time of occurance of Cmax of retigabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>t1/2 of retigabine</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Terminal phase half-life of retigabine</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Number of participants with adverse events as a measure of safety and tolerability (evaluated by the result of Clinical safety laboratory tests, vital signs, 12-lead ECG, telemetry and clinical monitoring/observation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ of NAMR</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of NAMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of NAMR</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Maximum observed concentration of NAMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of NAMR</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Time of occurance of Cmax of NAMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 of NAMR</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Terminal phase half-life of NAMR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fe</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Percent of retigabine and NAMR excreted in urine</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLr</measure>
    <time_frame>up to 96h post dose</time_frame>
    <description>Renal clearance of retigabine and NAMR</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Epilepsy, Partial</condition>
  <arm_group>
    <arm_group_label>Japanese</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Retigabine 300mg single-dose</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Caucasian</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Retigabine 300mg single-dose</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Retigabine</intervention_name>
    <description>Retigabine</description>
    <arm_group_label>Caucasian</arm_group_label>
    <arm_group_label>Japanese</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male subject between 20 and 45 years of age inclusive, at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  Japanese ancestry defined as being born in Japan, having four ethnic Japanese&#xD;
             grandparents, holding a Japanese passport or identity papers and being able to speak&#xD;
             Japanese. OR Caucasian defined as an individual having four grandparents who are all&#xD;
             descendents of the original people of Europe.&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician, based on a medical&#xD;
             evaluation including medical history, physical examination, laboratory tests and&#xD;
             12-lead ECG. A subject with a clinical abnormality or laboratory parameters outside&#xD;
             the reference range for the population being studied may be included only if the&#xD;
             Investigator and the GSK Medical Monitor agree that the finding is unlikely to&#xD;
             introduce additional risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Body weight ≥ 50 kg and BMI within the range 18.5 - 24.9 kg/m2 (inclusive).&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods listed separately. This criterion must be followed from the&#xD;
             time of the first dose of study medication until 1 week post-last dose&#xD;
&#xD;
          -  Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the consent form.&#xD;
&#xD;
          -  AST, ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin &gt;1.5xULN is&#xD;
             acceptable if bilirubin is fractionated and direct bilirubin &lt;35%).&#xD;
&#xD;
          -  Single QTcB or QTcF&lt; 450 msec; or QTc &lt; 480 msec in subjects with Bundle Branch Block.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subject has made a suicide attempt in the past or, in the investigator's judgment,&#xD;
             poses a significant suicide risk. Evidence of serious suicide risk may include any&#xD;
             history of suicidal behavior in the past 6 months and/or any suicidal ideation of type&#xD;
             4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS).&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen, Hepatitis C antibody or HIV&#xD;
             antigen/antibody result within 3 months of screening&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones).&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as: An&#xD;
             average weekly intake of &gt;14 drinks for males or &gt;7 drinks for females. One drink is&#xD;
             equivalent to 12 g of alcohol: 360 ml of beer, 150 ml of table wine or 45 ml of 80&#xD;
             proof distilled spirits.&#xD;
&#xD;
          -  The subject has participated in a clinical trial and has received an investigational&#xD;
             product within the following time period prior to the first dosing day in the current&#xD;
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Unable to refrain from the use of prescription or non-prescription drugs, including&#xD;
             vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or&#xD;
             14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is&#xD;
             longer) prior to the first dose of study medication, unless in the opinion of the&#xD;
             Investigator and GSK Medical Monitor the medication will not interfere with the study&#xD;
             procedures or compromise subject safety.&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, or components thereof or a&#xD;
             history of drug or other allergy that, in the opinion of the investigator or GSK&#xD;
             Medical Monitor, contraindicates their participation.&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within 56 day period.&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol.&#xD;
&#xD;
          -  Subject is mentally or legally incapacitated.&#xD;
&#xD;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia.&#xD;
&#xD;
          -  Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or&#xD;
             nicotine-containing products within 6 months prior to screening.&#xD;
&#xD;
          -  Unable to refrain from consumption of red wine, seville oranges, grapefruit or&#xD;
             grapefruit juice from 7 days prior to the first dose of study medication.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>45 Years</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>Kagoshima</city>
        <zip>890-0081</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>September 13, 2012</study_first_submitted>
  <study_first_submitted_qc>September 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2012</study_first_posted>
  <last_update_submitted>September 13, 2018</last_update_submitted>
  <last_update_submitted_qc>September 13, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">September 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Epilepsies, Partial</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ezogabine</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT01691872
org study id: 116247
nct id: NCT01691872
lead sponsor: 
has dmc: No
This is an open-label, single centre, parallel group study to evaluate the safety and
      pharmacokinetics of single oral doses of retigabine XR formulation in healthy adult Japanese
      subjects. To compare the pharmacokinetic and safety profile, Caucasian subjects are also
      incorporated. This study is intended to facilitate inclusion of Japanese patients in the
      global phase III program for retigabine XR formulation.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: AUC0-∞ of retigabine
time frame: up to 96h post dose
description: Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of retigabine
measure: Cmax of retigabine
time frame: up to 96h post dose
description: Maximum observed concentration of retigabine
measure: Tmax of retigabine
time frame: up to 96h post dose
description: Time of occurance of Cmax of retigabine
measure: t1/2 of retigabine
time frame: up to 96h post dose
description: Terminal phase half-life of retigabine
measure: Adverse Events
time frame: up to 96h post dose
description: Number of participants with adverse events as a measure of safety and tolerability (evaluated by the result of Clinical safety laboratory tests, vital signs, 12-lead ECG, telemetry and clinical monitoring/observation
measure: AUC0-∞ of NAMR
time frame: up to 96h post dose
description: Area under the concentration-time curve from pre-dose to last time of quantifiable concentration of NAMR
measure: Cmax of NAMR
time frame: up to 96h post dose
description: Maximum observed concentration of NAMR
measure: Tmax of NAMR
time frame: up to 96h post dose
description: Time of occurance of Cmax of NAMR
measure: t1/2 of NAMR
time frame: up to 96h post dose
description: Terminal phase half-life of NAMR
measure: fe
time frame: up to 96h post dose
description: Percent of retigabine and NAMR excreted in urine
measure: CLr
time frame: up to 96h post dose
description: Renal clearance of retigabine and NAMR
arm group label: Japanese
arm group type: Experimental
description: Retigabine 300mg single-dose
arm group label: Caucasian
arm group type: Experimental
description: Retigabine 300mg single-dose
intervention type: Drug
intervention name: Retigabine
description: Retigabine
arm group label: Caucasian
arm group label: Japanese
criteria: 
gender: Male
minimum age: 20 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: Japan
responsible party type: Sponsor
mesh term: Epilepsies, Partial
mesh term: Ezogabine