<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/NCT02262689</url>
  </required_header>
  <id_info>
    <org_study_id>201402</org_study_id>
    <nct_id>NCT02262689</nct_id>
  </id_info>
  <brief_title>To Evaluate Effects of GSK2256294 on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions</brief_title>
  <official_title>A Randomised Placebo-controlled Study to Evaluate the Effects of GSK2256294 Following Repeat Dosing on Pulmonary Artery Pressure in Healthy Volunteers Under Normoxic and Hypoxic Conditions</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Parexel</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery&#xD;
      systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of&#xD;
      dosing. It is single centre, double blind, randomized, placebo-controlled study to be&#xD;
      conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30&#xD;
      days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days&#xD;
      in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will occur&#xD;
      at home. Subjects will return to the unit on the evening of Day 6 and remain there until Day&#xD;
      8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1 pre-dose and on&#xD;
      Day 7 post-dose. Subject will be followed up for 28- 32 days after discharge. The maximum&#xD;
      estimated time that a subject will be enrolled in the study is 62 days from the screening&#xD;
      visit to follow up.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 8, 2015</start_date>
  <completion_date type="Actual">April 24, 2015</completion_date>
  <primary_completion_date type="Actual">April 24, 2015</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>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from baseline of PASP under hypoxic conditions</measure>
    <time_frame>Day 1 and Day 7</time_frame>
    <description>PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline of PASP under normoxic conditions</measure>
    <time_frame>Day 1 and Day 7</time_frame>
    <description>The PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under normoxic conditions following 7 days of GSK2256294 15 mg once daily. Change from baseline was calculated as the Day 7 value minus Day 1 value.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with Adverse events (AEs)</measure>
    <time_frame>Up to Day 32</time_frame>
    <description>An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of 12-lead electrocardiogram (ECG)</measure>
    <time_frame>Up to Day 32</time_frame>
    <description>Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of vital sign measurements</measure>
    <time_frame>Up to Day 32</time_frame>
    <description>Vital sign assessments includes temperature, blood pressure (systolic and diastolic) and pulse rate. measurements</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of physical examination findings</measure>
    <time_frame>Up to Day 32</time_frame>
    <description>A complete physical examination will include, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include, at a minimum assessments of the lungs, cardiovascular system, and abdomen (liver and spleen).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of clinical laboratory parameters</measure>
    <time_frame>Up to Day 32</time_frame>
    <description>Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">30</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>GSK2256294 15 mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Randomised subjects will be instructed to take three capsules of GSK2256294 15 mg, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Randomised subjects will be instructed to take three capsules of matching placebo, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2256294</intervention_name>
    <description>GSK2256294 will be supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg</description>
    <arm_group_label>GSK2256294 15 mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matched Placebo will be supplied as gelatin capsule to be administered orally</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  AGE: Between 18 and 65 years of age inclusive, at the time of signing the informed&#xD;
             consent&#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 according to site standards&#xD;
&#xD;
          -  Healthy as determined by the investigator or medically qualified designee based on a&#xD;
             medical evaluation including medical history, physical examination, laboratory tests&#xD;
             and cardiac monitoring.&#xD;
&#xD;
          -  A subject with a clinical abnormality or laboratory parameter(s) which is/are not&#xD;
             specifically listed in the inclusion or exclusion criteria, outside the reference&#xD;
             range for the population being studied may be included only if the investigator [in&#xD;
             consultation with the Medical Monitor if required] agree and document that the finding&#xD;
             is unlikely to introduce additional risk factors and will not interfere with the study&#xD;
             procedures.&#xD;
&#xD;
          -  Body weight &gt;= 60 kilogram and body mass index within the range 19 - 35 kilogram per&#xD;
             square meter (inclusive)&#xD;
&#xD;
          -  Female subject is eligible to participate if she is of non-reproductive potential&#xD;
             defined as: Pre-menopausal females with one of the following: documented tubal&#xD;
             ligation, documented hysteroscopic tubal occlusion procedure with follow-up&#xD;
             confirmation of bilateral tubal occlusion, hysterectomy, and documented bilateral&#xD;
             oophorectomy. Postmenopausal criteria is defined as 12 months of spontaneous&#xD;
             amenorrhea [in questionable cases a blood sample with simultaneous follicle&#xD;
             stimulating hormone (FSH) and estradiol levels consistent with menopause (refer to&#xD;
             laboratory reference ranges for confirmatory levels)]; females on hormone replacement&#xD;
             therapy (HRT) must discontinue their HRT before the start of the study; for those&#xD;
             whose menopausal status is in doubt, they will be required to use one of the highly&#xD;
             effective contraception methods and may need to have a blood sample taken to check&#xD;
             FSH/estradiol levels.&#xD;
&#xD;
          -  Male subjects with female partners of child bearing potential must comply with the&#xD;
             following contraception requirements from the time of first dose of study medication&#xD;
             until two weeks after the last dose of study medication; vasectomy with documentation&#xD;
             of azoospermia; male condom plus partner use of one of the contraceptive options&#xD;
             below: Contraceptive subdermal implant that meets the Standard Operating Procedure&#xD;
             (SOP)effectiveness criteria including a &lt;1% rate of failure per year, as stated in the&#xD;
             product label, Intrauterine device or intrauterine system that meets SOP effectiveness&#xD;
             criteria including a &lt;1% rate of failure per year, as stated in the product label,&#xD;
             Oral Contraceptive, either combined or progestogen alone, Injectable progestogen,&#xD;
             Contraceptive vaginal ring; percutaneous contraceptive patches. These allowed methods&#xD;
             of contraception are only effective when used consistently, correctly and in&#xD;
             accordance with the product label. The investigator is responsible for ensuring that&#xD;
             subjects understand how to properly use these methods of contraception.&#xD;
&#xD;
          -  Capable of giving signed informed consent as described in protocol, which includes&#xD;
             compliance with the requirements and restrictions listed in the consent form and in&#xD;
             protocol&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with sickle cell trait.&#xD;
&#xD;
          -  History of pulmonary hypertension.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) and bilirubin &gt;1.5x Upper limit of normal (ULN)&#xD;
             (isolated bilirubin &gt;1.5xULN is acceptable if bilirubin is fractionated and direct&#xD;
             bilirubin &lt;35%).&#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;
          -  QTcF &gt; 450 milliseconds (msec) NOTE: The QTc is the QT interval corrected for heart&#xD;
             rate according to Fridericia's formula (QTcF). The specific formula that will be used&#xD;
             to determine eligibility and discontinuation for an individual subject should be&#xD;
             determined prior to initiation of the study. In other words, several different&#xD;
             formulae cannot be used to calculate the QTc for an individual subject and then the&#xD;
             lowest QTc value used to include or discontinue the subject from the trial. For&#xD;
             purposes of data analysis, QTcF will be used as specified in the Reporting and&#xD;
             Analysis Plan (RAP).&#xD;
&#xD;
          -  Permitted Medications and Non-Drug Therapies: Acetaminophen, at doses of =&lt; 2&#xD;
             grams/day is permitted for use any time during the study. Other concomitant medication&#xD;
             may be considered on a case by case basis by the investigator in consultation with the&#xD;
             GSK Medical Monitor. All concomitant medications taken during the study will be&#xD;
             recorded in the case report form. The minimum requirement is that drug name, dose&#xD;
             administered and the dates of administration be recorded.&#xD;
&#xD;
          -  Prohibited Medications and Non-Drug Therapies: Subjects must abstain from taking&#xD;
             prescription or non-prescription drugs (including vitamins and dietary or herbal&#xD;
             supplements), within 7 days (or 14 days if the drug is a potential enzyme inducer) or&#xD;
             5 half-lives (whichever is longer) prior to the first dose of study medication until&#xD;
             completion of the follow-up visit, unless in the opinion of the Investigator and&#xD;
             sponsor the medication will not interfere with the study. - History of regular alcohol&#xD;
             consumption within 6 months of the study defined as: For US sites: an average weekly&#xD;
             intake of &gt;14 drinks for males or &gt;7 drinks for females. One drink is equivalent to 12&#xD;
             grams of alcohol: 12 ounces (360 milliliter [ml]) of beer, 5 ounces (150 ml) of wine&#xD;
             or 1.5 ounces (45 ml) of 80 proof distilled spirits.&#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;
          -  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 Medical&#xD;
             Monitor, contraindicates their participation&#xD;
&#xD;
          -  Presence of hepatitis B surface antigen (HBsAg), positive hepatitis C antibody test&#xD;
             result at screening or within 3 months prior to first dose of study treatment. For&#xD;
             potent immunosuppressive agents, subjects with presence of hepatitis B core antibody&#xD;
             (HBcAb) should also be excluded.&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  A positive test for Human Immunodeficiency Virus (HIV) antibody.&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within 56 days.&#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;
      </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>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>May 2017</verification_date>
  <study_first_submitted>October 9, 2014</study_first_submitted>
  <study_first_submitted_qc>October 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <last_update_submitted>May 5, 2017</last_update_submitted>
  <last_update_submitted_qc>May 5, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GSK2256294</keyword>
  <keyword>normoxic</keyword>
  <keyword>hypoxic</keyword>
  <keyword>Pulmonary artery systolic pressure (PASP)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Disease, Chronic Obstructive</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>201402</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>201402</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>201402</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>201402</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>201402</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>201402</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>201402</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_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/NCT02262689
org study id: 201402
nct id: NCT02262689
lead sponsor: 
collaborator: 
has dmc: No
The study evaluates the effect of GSK2256294 exposure at steady state on pulmonary artery
      systolic pressure (PASP) in healthy volunteers, under hypoxic conditions, after 7 days of
      dosing. It is single centre, double blind, randomized, placebo-controlled study to be
      conducted in approximately 30 healthy volunteers. Subjects will be screened no more than 30
      days. Subject will be admitted in clinical unit on Day -1. Subject will be dosed for 7 days
      in unit in morning on all days except for dosing on Days 3 -6. Dosing on Days 3 -6 will occur
      at home. Subjects will return to the unit on the evening of Day 6 and remain there until Day
      8. Subjects will undergo echocardiography under normoxic and hypoxic on Day 1 pre-dose and on
      Day 7 post-dose. Subject will be followed up for 28- 32 days after discharge. The maximum
      estimated time that a subject will be enrolled in the study is 62 days from the screening
      visit to follow up.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change from baseline of PASP under hypoxic conditions
time frame: Day 1 and Day 7
description: PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under hypoxic conditions following 7 days of GSK2256294 15 milligrams (mg) once daily. Change from baseline was calculated as the Day 7 value minus the Day1 value.
measure: Change from baseline of PASP under normoxic conditions
time frame: Day 1 and Day 7
description: The PASP is an indicator of cardiac hemodynamic status and is non-invasively estimated by echocardiography. Change from baseline in PASP under normoxic conditions following 7 days of GSK2256294 15 mg once daily. Change from baseline was calculated as the Day 7 value minus Day 1 value.
measure: Number of subjects with Adverse events (AEs)
time frame: Up to Day 32
description: An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
measure: Assessment of 12-lead electrocardiogram (ECG)
time frame: Up to Day 32
description: Triplicate 12-lead ECGs will be obtained at each time point using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals
measure: Assessment of vital sign measurements
time frame: Up to Day 32
description: Vital sign assessments includes temperature, blood pressure (systolic and diastolic) and pulse rate. measurements
measure: Assessment of physical examination findings
time frame: Up to Day 32
description: A complete physical examination will include, at a minimum, assessment of the Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height and weight will also be measured and recorded. A brief physical examination will include, at a minimum assessments of the lungs, cardiovascular system, and abdomen (liver and spleen).
measure: Assessment of clinical laboratory parameters
time frame: Up to Day 32
description: Clinical laboratory parameters includes haematology, clinical chemistry and urinalysis
arm group label: GSK2256294 15 mg
arm group type: Experimental
description: Randomised subjects will be instructed to take three capsules of GSK2256294 15 mg, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose.
arm group label: Placebo
arm group type: Placebo Comparator
description: Randomised subjects will be instructed to take three capsules of matching placebo, each morning for 7 days. Subjects will undergo echocardiography under normoxic and hypoxic conditions on Day 1 pre-dose and on Day 7 post-dose.
intervention type: Drug
intervention name: GSK2256294
description: GSK2256294 will be supplied as gelatin capsule to be administered orally with the unit dose 5 mg / dose level 15 mg
arm group label: GSK2256294 15 mg
intervention type: Drug
intervention name: Placebo
description: Matched Placebo will be supplied as gelatin capsule to be administered orally
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 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
mesh term: Pulmonary Disease, Chronic Obstructive
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: 