<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/NCT01702467</url>
  </required_header>
  <id_info>
    <org_study_id>116698</org_study_id>
    <nct_id>NCT01702467</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers</brief_title>
  <official_title>A Single-Blind, Randomized, Placebo-Controlled Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single, Oral Escalating Doses of GSK2647544 in Healthy Volunteers</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>
      The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and&#xD;
      plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a&#xD;
      randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose&#xD;
      design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each&#xD;
      potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 19, 2012</start_date>
  <completion_date type="Actual">May 15, 2013</completion_date>
  <primary_completion_date type="Actual">May 15, 2013</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s</measure>
    <time_frame>5 days in each of the 4 dosing session</time_frame>
    <description>Safety and tolerability parameters will include recording of AEs</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values</measure>
    <time_frame>5 days in each of the 4 dosing session</time_frame>
    <description>Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day -1, Day 3 and Follow-up (7-14 days post-last dose)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings</measure>
    <time_frame>5 days in each of the 4 dosing session</time_frame>
    <description>Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1, Day 2, Day 3 and Follow-up (7-14 days post-last dose)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters</measure>
    <time_frame>3 Days in each of the 4 dosing session</time_frame>
    <description>Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 48 hours post-dosing</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs</measure>
    <time_frame>5 days in each of the 4 dosing session</time_frame>
    <description>Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Follow-up (7-14 days post-last dose)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>5 days in each of the 4 dosing session</time_frame>
    <description>C-SSRS will be measured at Screening, Day -1, Day 1 (conducted prior to discharge) and Follow-up (7-14 days post-last dose)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak plasma concentration (Cmax) of GSK2647544</measure>
    <time_frame>4 Days in each of the 4 dosing session</time_frame>
    <description>To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of peak plasma concentration (tmax) of GSK2647544</measure>
    <time_frame>4 Days in each of the 4 dosing session</time_frame>
    <description>To assess PK profile of GSK2647544 tmax of GSK2647544 will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the time concentration curve (AUC) of GSK2647544</measure>
    <time_frame>4 Days in each of the 4 dosing session</time_frame>
    <description>To assess PK profile of GSK2647544 AUC of GSK2647544 will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t½ ) of GSK2647544</measure>
    <time_frame>4 Days in each of the 4 dosing session</time_frame>
    <description>To assess PK profile of GSK2647544 t½ of GSK2647544 will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent oral clearance (CL/F) of GSK2647544</measure>
    <time_frame>4 Days in each of the 4 dosing session</time_frame>
    <description>To assess PK profile of GSK2647544 CL/F of GSK2647544 will be measured</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity</measure>
    <time_frame>5 Days in each of the 4 dosing session</time_frame>
    <description>It will be measured at Day 1, Day 2, Day 3, Day 4 and Day 5</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">27</enrollment>
  <condition>Alzheimer's Disease</condition>
  <arm_group>
    <arm_group_label>GSK2647544</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The starting dose of GSK2647544 is 0.5 mg. The escalating doses to be administered will be determined based on study results from previous dose (s).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matching placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2647544</intervention_name>
    <description>Capsules containing 0.5mg to 50mg of GSK2647544.</description>
    <arm_group_label>GSK2647544</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo capsules.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy males who are 18 to 55 years of age, inclusive&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician&#xD;
&#xD;
          -  aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and&#xD;
             bilirubin &lt;= 1.5xUpper Limit of Normal (ULN)&#xD;
&#xD;
          -  Average of triplicate QTcB values and average of triplicate QTcF values must both &lt;&#xD;
             450 millisecond (msec)&#xD;
&#xD;
          -  Body weight &gt; 50 kg (110 pounds) and body mass index (BMI) between 19 and 30&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods&#xD;
&#xD;
          -  Capable of giving written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Those with Lp-PLA2 activity &lt;=20 nanomole/minute/milliliter (mL)(for subjects with 2&#xD;
             known birth parents of at least 50% Japanese, Chinese, or Korean ancestry)&#xD;
&#xD;
          -  History of asthma, anaphylaxis or anaphalactoid reactions, severe allergic responses&#xD;
&#xD;
          -  History of hypercoagulable state or history of thrombosis&#xD;
&#xD;
          -  A history of biliary tract disease including a history of liver disease with elevated&#xD;
             liver function tests of known or unknown etiology&#xD;
&#xD;
          -  Positive Human immunodeficiency virus (HIV), Hepatitis B or Hepatitis C at screening&#xD;
&#xD;
          -  History of regular use of tobacco- or nicotine-containing products within three months&#xD;
             of the study and/or has a positive breath CO at screening&#xD;
&#xD;
          -  History of alcohol consumption exceeding, on average, 21 drinks/week for men (1 drink&#xD;
             = 100 mL of wine or 240 mL of beer or 30 mL of hard liquor in Australia) within 6&#xD;
             months of the first dose of study medication&#xD;
&#xD;
          -  Positive urine drug or positive breath alcohol test at screening or at admission to&#xD;
             Clinical Research Unit&#xD;
&#xD;
          -  Unable to refrain from use of prescription or non-prescription drugs and vitamins&#xD;
             within 7 days or 5 half-lives (whichever is longer) prior to administration of study&#xD;
&#xD;
          -  Unable to refrain from use of dietary/herbal supplements including (but not limited&#xD;
             to) St. John's wort, kava, ephedra (ma huang), gingko biloba, DHEA, yohimbe, saw&#xD;
             palmetto, ginseng and red yeast rice within 14 days prior to treatment with study&#xD;
             medication&#xD;
&#xD;
          -  Treatment with an investigational drug within 30 days or 5 half-lives (whichever is&#xD;
             longer) prior to dosing&#xD;
&#xD;
          -  Unable to refrain from consumption of grapefruit or grapefruit juice within 7 days&#xD;
             prior to the first dose of study medication&#xD;
&#xD;
          -  For male subjects, an unwillingness to abstain from sexual intercourse with pregnant&#xD;
             or lactating women or an unwillingness to use a condom plus partner use of a highly&#xD;
             effective contraceptive if engaging in sexual intercourse with a woman who could&#xD;
             become pregnant until discharge from the study&#xD;
&#xD;
          -  Donation of blood in excess of 500 mL within 56 days prior to dosing&#xD;
&#xD;
          -  History of sensitivity to heparin or heparin-induced thrombocytopenia&#xD;
&#xD;
          -  Subjects, who in the investigator's judgement, pose a significant suicide risk.&#xD;
             Evidence of serious suicide risk may include any history of suicidal behaviour and/or&#xD;
             any suicidal ideation of type 4 or 5 on the C-SSRS in the last 6 months&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 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>Randwick</city>
        <state>New South Wales</state>
        <zip>2031</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>October 4, 2012</study_first_submitted>
  <study_first_submitted_qc>October 4, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2012</study_first_posted>
  <last_update_submitted>October 16, 2017</last_update_submitted>
  <last_update_submitted_qc>October 16, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Lp-PLA2</keyword>
  <keyword>Alzheimer's disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alzheimer Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116698</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
  </study_docs>
  <!-- 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/NCT01702467
org study id: 116698
nct id: NCT01702467
lead sponsor: 
has dmc: No
The current study will examine the safety, tolerability, plasma pharmacokinetics (PK), and
      plasma pharmacodynamics (PD) of single-doses of GSK2647544.The study will be conducted as a
      randomized, single-blind, placebo controlled, 4-way crossover single oral ascending dose
      design in 2 independent cohorts, eight healthy male subjects in each of the cohorts. Each
      potential subject will undergo Screening visit, Treatment Phase and Follow-up visit.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Safety and tolerability of GSK2647544 as assessed by number of subjects with adverse events (AE)s
time frame: 5 days in each of the 4 dosing session
description: Safety and tolerability parameters will include recording of AEs
measure: Safety and tolerability of GSK2647544 as assessed by change from Baseline in laboratory values
time frame: 5 days in each of the 4 dosing session
description: Safety and tolerability parameters will include laboratory (haematology, clinical chemistry, urinalysis) values at Screening, Day -1, Day 3 and Follow-up (7-14 days post-last dose)
measure: Safety and tolerability of GSK2647544 as assessed by change from Baseline in ECG readings
time frame: 5 days in each of the 4 dosing session
description: Safety and tolerability parameter will include the electrocardiogram (ECG) readings at Screening, Day -1, Day 1, Day 2, Day 3 and Follow-up (7-14 days post-last dose)
measure: Safety and tolerability of GSK2647544 as assessed by change from Baseline in Telemetry ECG parameters
time frame: 3 Days in each of the 4 dosing session
description: Safety and tolerability parameter will include the Telemetry ECG readings from 30 minutes pre-dosing till 48 hours post-dosing
measure: Safety and tolerability of GSK2647544 as assessed by change from Baseline in vital signs
time frame: 5 days in each of the 4 dosing session
description: Vital signs measurement include systolic and diastolic blood pressure and pulse rate at Screening, Day -1, Day 1, Day 2, Day 3, Day 4 and Follow-up (7-14 days post-last dose)
measure: Safety and tolerability of GSK2647544 as assessed by using the Columbia Suicide Severity Rating Scale (C-SSRS)
time frame: 5 days in each of the 4 dosing session
description: C-SSRS will be measured at Screening, Day -1, Day 1 (conducted prior to discharge) and Follow-up (7-14 days post-last dose)
measure: Peak plasma concentration (Cmax) of GSK2647544
time frame: 4 Days in each of the 4 dosing session
description: To assess PK profile of GSK2647544, Cmax of GSK2647544 will be measured
measure: Time of peak plasma concentration (tmax) of GSK2647544
time frame: 4 Days in each of the 4 dosing session
description: To assess PK profile of GSK2647544 tmax of GSK2647544 will be measured
measure: Area under the time concentration curve (AUC) of GSK2647544
time frame: 4 Days in each of the 4 dosing session
description: To assess PK profile of GSK2647544 AUC of GSK2647544 will be measured
measure: Terminal half-life (t½ ) of GSK2647544
time frame: 4 Days in each of the 4 dosing session
description: To assess PK profile of GSK2647544 t½ of GSK2647544 will be measured
measure: Apparent oral clearance (CL/F) of GSK2647544
time frame: 4 Days in each of the 4 dosing session
description: To assess PK profile of GSK2647544 CL/F of GSK2647544 will be measured
measure: Predose plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) activity and postdose Lp-PLA2 activity
time frame: 5 Days in each of the 4 dosing session
description: It will be measured at Day 1, Day 2, Day 3, Day 4 and Day 5
arm group label: GSK2647544
arm group type: Experimental
description: The starting dose of GSK2647544 is 0.5 mg. The escalating doses to be administered will be determined based on study results from previous dose (s).
arm group label: Placebo
arm group type: Placebo Comparator
description: Matching placebo
intervention type: Drug
intervention name: GSK2647544
description: Capsules containing 0.5mg to 50mg of GSK2647544.
arm group label: GSK2647544
intervention type: Drug
intervention name: Placebo
description: Matching placebo capsules.
arm group label: Placebo
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: Australia
responsible party type: Sponsor
mesh term: Alzheimer Disease
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 
study doc: 