<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/NCT01673555</url>
  </required_header>
  <id_info>
    <org_study_id>116008</org_study_id>
    <nct_id>NCT01673555</nct_id>
  </id_info>
  <brief_title>Effects of GSK1278863A on Pulmonary Artery Pressure in Healthy Volunteers</brief_title>
  <official_title>A Randomized, Placebo-controlled, Study to Evaluate the Effects of GSK1278863A on Pulmonary Artery Pressure 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>
      This protocol is designed to explore whether short-term therapy with GSK1278863 affects PASP&#xD;
      under normoxic and hypoxic conditions in healthy volunteers. Healthy subjects will be&#xD;
      evaluated using echocardiography to estimate PASP based on the velocity of the tricuspid&#xD;
      regurgitant jet. Resting PASP will be assessed under normoxic (room air) conditions, as well&#xD;
      as after 30 minutes' exposure to 15% O2 before, during, and after short-term treatment with&#xD;
      GSK1278863.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-center, randomized, placebo-controlled, single-blinded (subjects and&#xD;
      investigators will be blinded, GSK internal personnel will not be blinded) study designed to&#xD;
      test whether short-term administration (5 days) of GSK1278863 affects PASP under normoxic and&#xD;
      hypoxic conditions in healthy volunteers. Approximately 45 healthy subjects with&#xD;
      mild-moderate baseline tricuspid regurgitation (sufficient to allow reliable assessment of&#xD;
      PASP) will be enrolled into this study and will provide ~15 evaluable subjects in each arm&#xD;
      [Placebo, 5 mg, and 100 mg GSK 1278863].&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 15, 2012</start_date>
  <completion_date type="Actual">November 19, 2012</completion_date>
  <primary_completion_date type="Actual">November 19, 2012</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>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Placebo-adjusted change from baseline in PASP (estimated by transthoracic echocardiography) under normoxic conditions following 5 days of GSK1278863</measure>
    <time_frame>Day 5</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the first dose of study treatment</measure>
    <time_frame>Day 1</time_frame>
    <description>8 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions following 1 day of therapy</measure>
    <time_frame>Day 1</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the fifth dose of study treatment</measure>
    <time_frame>Day 5</time_frame>
    <description>8 hours</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Placebo-adjusted change from baseline in PASP under hypoxic conditions following 5 days of GSK1278863</measure>
    <time_frame>Day 5</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical safety and tolerability data including AE reporting, ECGs, vital signs, physical exam findings and clinical laboratory values, including hematologic parameters</measure>
    <time_frame>Day 5</time_frame>
    <description>Through-out the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma pharmacokinetics (AUC, Cmax, Tmax, T1/2, etc.) of GSK1278863 and its circulating metabolites (M2, M3, M4, M5, M6 and M13)</measure>
    <time_frame>Day 5</time_frame>
    <description>Through-out the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RV size, RV ejection fraction, severity of tricuspid regurgitation, right ventricular outflow tract acceleration time at all time points at which echocardiograms are obtained (as data permit)</measure>
    <time_frame>Day 5</time_frame>
    <description>Exploratory outcomes; through-out the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biomarker/PD endpoints may include EPO, endothelin-1 and hepcidin or other markers of PHD or HIF activity, as data permit</measure>
    <time_frame>Day 5</time_frame>
    <description>Exploratory outcomes; through-out the study</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">49</enrollment>
  <condition>Anaemia</condition>
  <arm_group>
    <arm_group_label>GSK1278863 5mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK1278863 5mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GSK1278863 100mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>GSK1278863 100mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK1278863</intervention_name>
    <description>GSK1278863</description>
    <arm_group_label>GSK1278863 100mg</arm_group_label>
    <arm_group_label>GSK1278863 5mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  AST, ALT, alkaline phosphatase and bilirubin less than and equal to 1.5xULN (isolated&#xD;
             bilirubin greater than 1.5xULN is acceptable if bilirubin is fractionated and direct&#xD;
             bilirubin less than 35%).&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician, based on a medical&#xD;
             evaluation including [medical history, physical examination and laboratory tests]. A&#xD;
             subject with a clinical abnormality or laboratory parameters outside the reference&#xD;
             range for the population being studied may be included only if the Investigator and&#xD;
             the GSK Medical Monitor agree that the finding is unlikely to introduce additional&#xD;
             risk and will not interfere with the study procedures.&#xD;
&#xD;
          -  A hemoglobin value at screening between 13.5- 16 g/dL.&#xD;
&#xD;
          -  Male subjects between 18 and 55 years of age inclusive, at the time of signing the&#xD;
             informed consent.&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods listed in the protocol. This criterion must be followed from&#xD;
             the time of the first dose of study medication until the follow-up visit.&#xD;
&#xD;
          -  BMII less than and equal to 32 kg/m2&#xD;
&#xD;
          -  Single QTcB or QTcF less than 450 msec&#xD;
&#xD;
          -  Screening echocardiogram of at least good quality, without clinically significant&#xD;
             abnormalities, and with mild-moderate tricuspid regurgitation sufficient for the&#xD;
             reliable estimation of PASP, as determined by the echocardiography core laboratory or&#xD;
             responsible cardiologist.&#xD;
&#xD;
          -  Screening PASP within the normal range under normoxic conditions.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result.&#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;
          -  Any history of IV drug abuse.&#xD;
&#xD;
          -  A positive test for HIV antibody.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as: an&#xD;
             average weekly intake of greater than 14 drinks for males or greater than 7 drinks for&#xD;
             females. One drink is equivalent to 12 g of alcohol: 12 ounces (360 ml) of beer, 5&#xD;
             ounces (150 ml) of wine or 1.5 ounces (45 ml) of 80 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;
          -  Use of prescription or non-prescription drugs, including vitamins, herbal and dietary&#xD;
             supplements (including St John's Wort) within 7 days (or 14 days if the drug is a&#xD;
             potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first&#xD;
             dose of study medication, unless in the opinion of the Investigator and GSK Medical&#xD;
             Monitor the medication will not interfere with the study procedures or compromise&#xD;
             subject safety.&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within a 56 day period.&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol.&#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;
          -  Strong family history of malignancy.&#xD;
&#xD;
          -  Subjects with sickle cell trait.&#xD;
&#xD;
          -  History of pulmonary hypertension&#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>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>July 12, 2012</study_first_submitted>
  <study_first_submitted_qc>August 23, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>June 7, 2017</last_update_submitted>
  <last_update_submitted_qc>June 7, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GSK1278863</keyword>
  <keyword>Pulmonary artery pressure</keyword>
  <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>116008</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_doc>
      <doc_id>116008</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>116008</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>116008</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>116008</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>116008</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>116008</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_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/NCT01673555
org study id: 116008
nct id: NCT01673555
lead sponsor: 
has dmc: No
This protocol is designed to explore whether short-term therapy with GSK1278863 affects PASP
      under normoxic and hypoxic conditions in healthy volunteers. Healthy subjects will be
      evaluated using echocardiography to estimate PASP based on the velocity of the tricuspid
      regurgitant jet. Resting PASP will be assessed under normoxic (room air) conditions, as well
      as after 30 minutes' exposure to 15% O2 before, during, and after short-term treatment with
      GSK1278863.
This is a single-center, randomized, placebo-controlled, single-blinded (subjects and
      investigators will be blinded, GSK internal personnel will not be blinded) study designed to
      test whether short-term administration (5 days) of GSK1278863 affects PASP under normoxic and
      hypoxic conditions in healthy volunteers. Approximately 45 healthy subjects with
      mild-moderate baseline tricuspid regurgitation (sufficient to allow reliable assessment of
      PASP) will be enrolled into this study and will provide ~15 evaluable subjects in each arm
      [Placebo, 5 mg, and 100 mg GSK 1278863].
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: Single (Participant)
measure: Placebo-adjusted change from baseline in PASP (estimated by transthoracic echocardiography) under normoxic conditions following 5 days of GSK1278863
time frame: Day 5
measure: Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the first dose of study treatment
time frame: Day 1
description: 8 hours
measure: Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions following 1 day of therapy
time frame: Day 1
measure: Placebo-adjusted change from baseline in PASP under normoxic and hypoxic conditions 8 hours after the fifth dose of study treatment
time frame: Day 5
description: 8 hours
measure: Placebo-adjusted change from baseline in PASP under hypoxic conditions following 5 days of GSK1278863
time frame: Day 5
measure: Clinical safety and tolerability data including AE reporting, ECGs, vital signs, physical exam findings and clinical laboratory values, including hematologic parameters
time frame: Day 5
description: Through-out the study
measure: Plasma pharmacokinetics (AUC, Cmax, Tmax, T1/2, etc.) of GSK1278863 and its circulating metabolites (M2, M3, M4, M5, M6 and M13)
time frame: Day 5
description: Through-out the study
measure: RV size, RV ejection fraction, severity of tricuspid regurgitation, right ventricular outflow tract acceleration time at all time points at which echocardiograms are obtained (as data permit)
time frame: Day 5
description: Exploratory outcomes; through-out the study
measure: Biomarker/PD endpoints may include EPO, endothelin-1 and hepcidin or other markers of PHD or HIF activity, as data permit
time frame: Day 5
description: Exploratory outcomes; through-out the study
arm group label: GSK1278863 5mg
arm group type: Experimental
description: GSK1278863 5mg
arm group label: GSK1278863 100mg
arm group type: Experimental
description: GSK1278863 100mg
arm group label: Placebo
arm group type: Placebo Comparator
description: Placebo
intervention type: Drug
intervention name: GSK1278863
description: GSK1278863
arm group label: GSK1278863 100mg
arm group label: GSK1278863 5mg
intervention type: Drug
intervention name: Placebo
description: Placebo
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: United States
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
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: 