<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/NCT01721135</url>
  </required_header>
  <id_info>
    <org_study_id>112360</org_study_id>
    <nct_id>NCT01721135</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effect of Two Different Repeat Doses of GSK2190915 on the QTc Interval.</brief_title>
  <official_title>A Randomised, Placebo Controlled, Four-way Cross-over Study to Assess Cardiac Re-polarisation Following Repeat Dosing With GSK2190915 and Placebo for Five Days, With Moxifloxacin as a Positive Control, in Healthy Male and Female 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 study is a randomized, placebo controlled, four way crossover, in which the the effect&#xD;
      of GSK2190915 on the QTc interval is assessed. Healthy subjects will recieve a 5 day course&#xD;
      of each of the following; oral placebo, GSK2190915 100mg, GSK2190915 1000mg and moxifloxacin&#xD;
      400mg (single dose) with a weeks washout prior to starting the next course. Key assessments&#xD;
      include a 12- lead electrocardiogram and pharmacokinetic testing. Safety will be assessed by&#xD;
      blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events&#xD;
      .&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, placebo controlled, four way crossover thorough QT study to evaluate&#xD;
      the effect of repeat dose GSK2190915 on the QTc interval in healthy male and female subjects.&#xD;
      Approximately 48 subjects will receive oral placebo, GSK2190915 (100mg or 1000mg) and&#xD;
      moxifloxacin (400mg). GSK2190915 or matching placebo will be given once daily for 5 days with&#xD;
      a moxifloxacin matching placebo given on Day 5. Moxifloxacin (positive control) will be given&#xD;
      as a single-blind single dose on Day 5 with placebo administered on Days 1-4. Individual&#xD;
      time-matched changes from baseline in QTcF (difference from placebo) for GSK2190915 will be&#xD;
      determined 0-24 hours after dosing on Day 5 (primary endpoint). Secondary endpoints will&#xD;
      include changes from baseline in QTcF, QTcB and QT interval at each timepoint after 5 days&#xD;
      dosing of GSK2190915 and single dose moxifloxacin (400mg). Plasma concentrations on Day 5&#xD;
      (0-24 hours) and pharmacokinetic parameters of GSK2190915 will also be derived.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Study was terminated due to toxicology findings after screening started but before first&#xD;
    subject first dose.&#xD;
  </why_stopped>
  <start_date>September 2010</start_date>
  <completion_date type="Anticipated">December 2014</completion_date>
  <primary_completion_date type="Anticipated">December 2014</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg GSK2190915 as compared with time-matched placebo</measure>
    <time_frame>5 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 1000mg GSK2190915 as compared with time-matched placebo</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcB interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg and 1000mg GSK2190915 as compared with time-matched placebo</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for moxifloxacin as compared with time-matched placebo</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations of GSK2190915 taken on Day 5 to derive pharmacokinetic parameters including Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax) and Area under the concentration-time curve over the dosing interval (AUC(0-τ))</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart rate and ECG parameters taken on Day 1 and Day 5 compared with concentration of Plasma GSK2190915 to find relationship</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximal change from baseline on Day 5 for QTcF and QTcB</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline at each timepoint on Day 5 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of safety and tolerability of GSK2190915 by 12-lead ECGs, vital signs, adverse events and clinical laboratory tests throughout treatment period</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>GSK2190915 100mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK2190915 100mg on days 1-5; moxifloxacin placebo on day 5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GSK2190915 1000mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK2190915 1000mg on days 1-5; moxifloxacin placebo on day 5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>moxifloxacin 400mg</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>placebo tablet on days 1-5; moxifloxacin 400mg on day 5</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>placebo tablet on days 1-5; moxifloxacin placebo on day 5</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2190915 100mg</intervention_name>
    <description>Film coated oral tablet</description>
    <arm_group_label>GSK2190915 100mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2190915 200mg</intervention_name>
    <description>Film coated oral tablet</description>
    <arm_group_label>GSK2190915 1000mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>moxifloxacin 400mg</intervention_name>
    <description>Film coated oral tablet</description>
    <arm_group_label>moxifloxacin 400mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>moxifloxacin placebo</intervention_name>
    <description>Film coated oral tablet</description>
    <arm_group_label>GSK2190915 1000mg</arm_group_label>
    <arm_group_label>GSK2190915 100mg</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2190915 placebo</intervention_name>
    <description>Film coated oral tablet</description>
    <arm_group_label>GSK2190915 100mg</arm_group_label>
    <arm_group_label>moxifloxacin 400mg</arm_group_label>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male or female between 18 and 65 years of age inclusive&#xD;
&#xD;
          -  Aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase&#xD;
             and bilirubin ≤ 1.5x Upper limit of normal (ULN)&#xD;
&#xD;
          -  Healthy as determined by a physician, based on a medical evaluation including medical&#xD;
             history, physical examination, laboratory tests and cardiac monitoring.&#xD;
&#xD;
          -  A female subject is eligible to participate if she is of: Non-childbearing potential&#xD;
             defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or&#xD;
             postmenopausal . Females on hormone replacement therapy (HRT) and whose menopausal&#xD;
             status is in doubt will be required to use one of the contraception methods. Those of&#xD;
             child-bearing potential must agree to use one of the protocol contraception methods.&#xD;
&#xD;
          -  Body mass index (BMI) within the range 18.5-29.0 kg/m2 (inclusive)&#xD;
&#xD;
          -  Capable of giving written informed consent&#xD;
&#xD;
          -  Current non-smokers who have not used tobacco products in the 6 month period preceding&#xD;
             screening&#xD;
&#xD;
          -  No significant abnormality on 12-lead electrocardiogram (ECG) at screening&#xD;
&#xD;
          -  A 24 hour Holter ECG at screening that demonstrates no clinically significant&#xD;
             abnormalities&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A physician deems the subject unsuitable for the study&#xD;
&#xD;
          -  A screening Holter ECG tracing that reveals clinically concerning arrhythmias&#xD;
&#xD;
          -  A blood pressure that is persistently higher than 140/90 millimetres of mercury (mmHg)&#xD;
             at screening.&#xD;
&#xD;
          -  A mean heart rate outside the range 40-90 beats per minute (bpm) at screening.&#xD;
&#xD;
          -  History or presence of any medically significant disease, or any disorder. In&#xD;
             particular, a family history of QT prolongation, of early or sudden cardiac death or&#xD;
             of early cardiovascular disease.&#xD;
&#xD;
          -  A positive result for Hepatitis B or Hepatitis C within 3 months of screening&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen&#xD;
&#xD;
          -  A positive test for Human Immunodeficiency Virus (HIV) antibody&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study&#xD;
&#xD;
          -  The subject has participated in a clinical trial and has received an investigational&#xD;
             product within 3 months of the first dosing day in the current study&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day&#xD;
&#xD;
          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary&#xD;
             supplements from 14 days before screening until the follow-up visit unless permitted&#xD;
             by the investigator&#xD;
&#xD;
          -  History of sensitivity to any of the study medications&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within a 3 month period&#xD;
&#xD;
          -  Pregnant females&#xD;
&#xD;
          -  Lactating females&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol&#xD;
&#xD;
          -  Subject is mentally or legally incapacitated&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 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>London</city>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>August 2013</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>
  <last_update_submitted>August 20, 2013</last_update_submitted>
  <last_update_submitted_qc>August 20, 2013</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 21, 2013</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>moxifloxacin</keyword>
  <keyword>GSK2190915</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>QTc</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Moxifloxacin</mesh_term>
    <mesh_term>Norgestimate, ethinyl estradiol drug combination</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/NCT01721135
org study id: 112360
nct id: NCT01721135
lead sponsor: 
has dmc: No
This study is a randomized, placebo controlled, four way crossover, in which the the effect
      of GSK2190915 on the QTc interval is assessed. Healthy subjects will recieve a 5 day course
      of each of the following; oral placebo, GSK2190915 100mg, GSK2190915 1000mg and moxifloxacin
      400mg (single dose) with a weeks washout prior to starting the next course. Key assessments
      include a 12- lead electrocardiogram and pharmacokinetic testing. Safety will be assessed by
      blood pressure, heart rate, clinical laboratory safety tests and collection of adverse events
      .
This is a randomized, placebo controlled, four way crossover thorough QT study to evaluate
      the effect of repeat dose GSK2190915 on the QTc interval in healthy male and female subjects.
      Approximately 48 subjects will receive oral placebo, GSK2190915 (100mg or 1000mg) and
      moxifloxacin (400mg). GSK2190915 or matching placebo will be given once daily for 5 days with
      a moxifloxacin matching placebo given on Day 5. Moxifloxacin (positive control) will be given
      as a single-blind single dose on Day 5 with placebo administered on Days 1-4. Individual
      time-matched changes from baseline in QTcF (difference from placebo) for GSK2190915 will be
      determined 0-24 hours after dosing on Day 5 (primary endpoint). Secondary endpoints will
      include changes from baseline in QTcF, QTcB and QT interval at each timepoint after 5 days
      dosing of GSK2190915 and single dose moxifloxacin (400mg). Plasma concentrations on Day 5
      (0-24 hours) and pharmacokinetic parameters of GSK2190915 will also be derived.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg GSK2190915 as compared with time-matched placebo
time frame: 5 days
measure: Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 1000mg GSK2190915 as compared with time-matched placebo
time frame: 5 days
measure: Change from baseline in QTcB interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for 100mg and 1000mg GSK2190915 as compared with time-matched placebo
time frame: 5 days
measure: Change from baseline in QTcF interval at each timepoint on Day 5 (average of at least 3 12-lead Holter ECG replicates per time point) for moxifloxacin as compared with time-matched placebo
time frame: 5 days
measure: Plasma concentrations of GSK2190915 taken on Day 5 to derive pharmacokinetic parameters including Maximum observed concentration (Cmax), Time of occurrence of Cmax (tmax) and Area under the concentration-time curve over the dosing interval (AUC(0-τ))
time frame: 5 days
measure: Heart rate and ECG parameters taken on Day 1 and Day 5 compared with concentration of Plasma GSK2190915 to find relationship
time frame: 5 days
measure: Maximal change from baseline on Day 5 for QTcF and QTcB
time frame: 5 days
measure: Change from baseline at each timepoint on Day 5 for other cardiac electrophysiological parameters: QT, QRS, RR, PR and ventricular rate
time frame: 5 days
measure: Assessment of safety and tolerability of GSK2190915 by 12-lead ECGs, vital signs, adverse events and clinical laboratory tests throughout treatment period
time frame: 5 days
arm group label: GSK2190915 100mg
arm group type: Experimental
description: GSK2190915 100mg on days 1-5; moxifloxacin placebo on day 5
arm group label: GSK2190915 1000mg
arm group type: Experimental
description: GSK2190915 1000mg on days 1-5; moxifloxacin placebo on day 5
arm group label: moxifloxacin 400mg
arm group type: Active Comparator
description: placebo tablet on days 1-5; moxifloxacin 400mg on day 5
arm group label: placebo
arm group type: Placebo Comparator
description: placebo tablet on days 1-5; moxifloxacin placebo on day 5
intervention type: Drug
intervention name: GSK2190915 100mg
description: Film coated oral tablet
arm group label: GSK2190915 100mg
intervention type: Drug
intervention name: GSK2190915 200mg
description: Film coated oral tablet
arm group label: GSK2190915 1000mg
intervention type: Drug
intervention name: moxifloxacin 400mg
description: Film coated oral tablet
arm group label: moxifloxacin 400mg
intervention type: Drug
intervention name: moxifloxacin placebo
description: Film coated oral tablet
arm group label: GSK2190915 1000mg
arm group label: GSK2190915 100mg
arm group label: placebo
intervention type: Drug
intervention name: GSK2190915 placebo
description: Film coated oral tablet
arm group label: GSK2190915 100mg
arm group label: moxifloxacin 400mg
arm group label: placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Moxifloxacin
mesh term: Norgestimate, ethinyl estradiol drug combination