xml: <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/NCT05999708</url>
    </required_header>
    <id_info>
      <org_study_id>218680</org_study_id>
      <nct_id>NCT05999708</nct_id>
    </id_info>
    <brief_title>A First Time in Human Study to Evaluate the Safety and Tolerability of GSK4381406 in Healthy Participants</brief_title>
    <official_title>A Randomized, Double-Blind, Placebo-Controlled, Single, Repeat Dose Escalation and Indomethacin Challenge Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK4381406 in Healthy Participants</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>GlaxoSmithKline</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>GlaxoSmithKline</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a 3-part First Time in Human (FTIH) study to evaluate the safety, tolerability, and&#xD;
        pharmacokinetics (PK) profile of GSK4381406 following administration of single ascending&#xD;
        doses (Part 1), repeat ascending doses (Part 2), and repeat doses with an indomethacin&#xD;
        challenge (Part 3) in healthy adult participants. Part 1 consists of 4 planned cohorts with&#xD;
        up to 2 treatment periods in each and is expected to have 6 doses (but can accommodate up to&#xD;
        7 doses). The impact of food on PK of GSK4381406 will also be assessed. Part 2 will&#xD;
        investigate 14 days of repeat dosing in 3 cohorts with 3 dose levels. Part 3 will evaluate&#xD;
        the impact of repeat doses of GSK4381406 versus placebo on indomethacin induced changes in&#xD;
        small intestinal permeability in healthy participants.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 28, 2023</start_date>
    <completion_date type="Anticipated">September 2, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 2, 2024</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>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Part 1 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 - Number of participants with clinically significant changes in hematology laboratory values</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with clinically significant changes in hematology laboratory values</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with clinically significant changes in hematology laboratory values</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 - Number of participants with clinically significant changes in chemistry laboratory values</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with clinically significant changes in chemistry laboratory values</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with clinically significant changes in chemistry laboratory values</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 - Number of participants with clinically significant changes in urinalysis</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with clinically significant changes in urinalysis</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with clinically significant changes in urinalysis</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 - Number of participants with clinically significant changes in vital signs</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with clinically significant changes in vital signs</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with clinically significant changes in vital signs</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 1 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings</measure>
      <time_frame>Up to Day 40</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 2 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings</measure>
      <time_frame>Up to Day 54</time_frame>
    </primary_outcome>
    <primary_outcome>
      <measure>Part 3 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings</measure>
      <time_frame>Up to Day 34</time_frame>
    </primary_outcome>
    <secondary_outcome>
      <measure>Part 1 - Area under the plasma concentration-time curve (AUC) from time zero to 24-hour post-dose [AUC(0-24)</measure>
      <time_frame>Up to 24 hours post dose</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - AUC from time zero to last quantifiable concentration [AUC(0-t)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - AUC from time zero to infinity [AUC(0-inf)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - Maximum observed plasma drug concentration (Cmax)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - Time to maximum observed plasma drug concentration (tmax)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - Time of last quantifiable concentration (tlast)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1 - Apparent terminal phase half-life (t½)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - AUC from time zero to last quantifiable concentration [AUC(0-t)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - AUC over the dosing interval [AUC(0-tau)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Maximum observed plasma drug concentration (Cmax)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Time to maximum observed plasma drug concentration (tmax)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - AUC from time zero to infinity [AUC(0-inf)</measure>
      <time_frame>Day 14 to Day 54</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Apparent terminal phase half-life (t½)</measure>
      <time_frame>Day 14 to Day 54</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Pre-dose (trough) plasma concentrations (Ctau)</measure>
      <time_frame>Day 1 to Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Accumulation ratios for Cmax (R)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 2 - Accumulation ratios for AUC(0-tau) (Ro)</measure>
      <time_frame>Day 1 and Day 14</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1: Cohort 4 - AUC from time zero to infinity [AUC(0-inf)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1: Cohort 4 - Maximum observed plasma drug concentration (Cmax)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 1: Cohort 4 - Time to maximum observed plasma drug concentration (tmax)</measure>
      <time_frame>Up to Day 40</time_frame>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Part 3 - Lactulose:rhamnose ratio over 0-5 hour in urine</measure>
      <time_frame>At Day 1, 3, 17 and 20</time_frame>
      <description>Lactulose and rhamnose concentrations in urine will be collected over 0-2 hour and 2-5 hour, which will be used to derive the ratio over 0-5 hour</description>
    </secondary_outcome>
    <number_of_arms>8</number_of_arms>
    <enrollment type="Anticipated">84</enrollment>
    <condition>Colitis, Ulcerative</condition>
    <arm_group>
      <arm_group_label>Part 1: Cohort 1 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 1 Cohort 1 will receive a single dose of GSK4381406 dose level 1 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 3 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1: Cohort 2 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 1 Cohort 2 will receive a single dose of GSK4381406 dose level 2 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 4 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1: Cohort 3 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 1 Cohort 3 will receive a single dose of GSK4381406 dose level 5 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 7 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose. Note: Requirement for Treatment Period 2 (dose level 7) will be determined by PK data of previous doses.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 1: Cohort 4 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 1 Cohort 4 will receive a single dose of GSK4381406 dose level 6 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 6 in Treatment Period 2 in fed state with washout period of at least 40 days between each dose.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Cohort 5 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 2 Cohort 5 will receive 14 days of once daily repeat dosing of GSK4381406 dose level A or placebo in fasted state.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Cohort 6 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 2 Cohort 6 will receive 14 days of once daily repeat dosing of GSK4381406 dose level B or placebo in fasted state.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 2: Cohort 7 - GSK4381406 or placebo</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 2 Cohort 7 will receive 14 days of once daily repeat dosing of GSK4381406 dose level C or placebo in fasted state.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Part 3 - GSK4381406 or Placebo and Indomethacin</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants in Part 3 will receive 3 days of once daily repeat dosing of GSK4381406 in Treatment Period 1 followed by placebo in Treatment Period 2, or placebo in Treatment Period 1 and GSK4381406 in Treatment Period 2 in a cross-over design with a washout period of at least 14 days between each dosing period. Participants will be dosed in fasted state. The participants will be challenged with indomethacin during the final 2 days of each dosing period.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>GSK4381406</intervention_name>
      <description>GSK4381406 will be administered.</description>
      <arm_group_label>Part 1: Cohort 1 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 2 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 3 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 4 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 5 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 6 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 7 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 3 - GSK4381406 or Placebo and Indomethacin</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Placebo will be administered.</description>
      <arm_group_label>Part 1: Cohort 1 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 2 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 3 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 1: Cohort 4 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 5 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 6 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 2: Cohort 7 - GSK4381406 or placebo</arm_group_label>
      <arm_group_label>Part 3 - GSK4381406 or Placebo and Indomethacin</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Indomethacin</intervention_name>
      <description>Indomethacin will be administered.</description>
      <arm_group_label>Part 3 - GSK4381406 or Placebo and Indomethacin</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Body weight greater than (&gt;)50 kg and body mass index (BMI) within the range 18-29.9&#xD;
               kilogram per meter square (kg/m^2) (inclusive)&#xD;
  &#xD;
            -  Male and female participants&#xD;
  &#xD;
            -  A female participant is eligible to participate if she is of non-childbearing&#xD;
               potential&#xD;
  &#xD;
            -  Capable of giving signed informed consent&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Medical history of cardiovascular, cerebrovascular (including transient ischemic&#xD;
               attack (TIA), ischemic and hemorrhagic stroke), respiratory, hepatic, renal (including&#xD;
               chronic kidney disease), gastrointestinal (including IBD and IBS), endocrine,&#xD;
               hematologic (including anemia and coagulopathies), or neurological disorders&#xD;
  &#xD;
            -  Abnormal blood pressure (BP) (defined as systolic BP greater than or equal to [≥]130&#xD;
               millimetres of mercury (mmHg) or diastolic BP ≥85 mmHg) measured (based on the average&#xD;
               of triplicate BP readings)&#xD;
  &#xD;
            -  Medical history of antihypertensive drugs&#xD;
  &#xD;
            -  Presence, or history within the past 14 days, of irregularities in bowel movements,&#xD;
               including diarrhea (the passage of 3 or more loose or liquid stools per day) and&#xD;
               constipation (3 or fewer bowel movements per week or requiring the use of laxatives).&#xD;
  &#xD;
            -  Symptomatic herpes zoster within 3 months prior to screening.&#xD;
  &#xD;
            -  Clinically significant multiple or severe drug allergies, intolerance to&#xD;
               corticosteroids, or severe post-treatment hypersensitivity reactions (including, but&#xD;
               not limited to, erythema multiforme major, linear immunoglobulin A [IgA] dermatosis,&#xD;
               toxic epidermal necrolysis, and exfoliative dermatitis).&#xD;
  &#xD;
            -  Any history or presence of malignancy except for basal cell or squamous epithelial&#xD;
               carcinomas of the skin.&#xD;
  &#xD;
            -  Alanine transaminase (ALT) &gt;1.5x Upper limit of normal (ULN)&#xD;
  &#xD;
            -  Total bilirubin &gt;1.5x ULN (isolated total bilirubin &gt;1.5xULN is acceptable if total&#xD;
               bilirubin is fractionated and direct bilirubin lesser than [&lt;]35 percentage [%]).&#xD;
  &#xD;
            -  Current or chronic history of liver disease or known hepatic or biliary abnormalities&#xD;
               (except for Gilbert's syndrome or asymptomatic gallstones).&#xD;
  &#xD;
            -  QT interval corrected for heart rate according to Fridericia's formula (QTcF) &gt;450&#xD;
               millisecond (msec)&#xD;
  &#xD;
            -  Unable to refrain from the use of over-the-counter or prescription medication,&#xD;
               including herbal medications and vitamins within 7 days or 5 half-lives (whichever is&#xD;
               longer) prior to dosing until after follow-up visit, unless in the opinion of the&#xD;
               Investigator and the GSK medical monitor, the medication will not interfere with the&#xD;
               study procedures or compromise participant safety&#xD;
  &#xD;
            -  Use of a systemic antimicrobial within 30 days of screening&#xD;
  &#xD;
            -  The use of NSAIDs, including aspirin, are not permitted throughout the study (except&#xD;
               on Part 3 Indomethacin challenge) and should not have been taken within 14 days&#xD;
               immediately preceding the first dose of study intervention. For analgesia, paracetamol&#xD;
               (acetaminophen) at doses of less than or equal to (≤)4 gram per day (g/day) is&#xD;
               permitted&#xD;
  &#xD;
            -  Unable to refrain from consumption of red wine, Seville oranges, grapefruit, or&#xD;
               grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit&#xD;
               juices from 7 days prior to first dose of study intervention until completion of the&#xD;
               follow up period&#xD;
  &#xD;
            -  Live vaccine(s) within 1 month prior to screening or plans to receive such vaccines&#xD;
               during the study&#xD;
  &#xD;
            -  Participation in the study would result in loss of blood or blood products in excess&#xD;
               of 450 millilitre (mL) within the last 3 months prior to the Screening Visit. Blood&#xD;
               donation during the study is not permitted&#xD;
  &#xD;
            -  Exposure to more than 4 new chemical entities within 12 months prior to the first&#xD;
               dosing day&#xD;
  &#xD;
            -  Current enrolment or past participation in another investigational study in which an&#xD;
               investigational intervention (e.g., drug, vaccine, invasive device) was administered&#xD;
               within the last 40 days or 5 half-lives, whichever is longer, before the first day of&#xD;
               dosing (Day 1)&#xD;
  &#xD;
            -  Presence of Hepatitis B surface antigen (HBsAg) at screening or within 3 months prior&#xD;
               to first dose of study intervention&#xD;
  &#xD;
            -  Positive hepatitis C antibody test result at screening or within 3 months prior to&#xD;
               first dose of study intervention&#xD;
  &#xD;
            -  Positive hepatitis C ribo nucleic acid (RNA) test result at screening or within 3&#xD;
               months prior to first dose of study intervention.&#xD;
  &#xD;
            -  Positive pre-study drug/alcohol screen&#xD;
  &#xD;
            -  Regular use of known drugs of abuse, including tetrahydrocannabinol.&#xD;
  &#xD;
            -  Positive human immunodeficiency virus (HIV) antibody test.&#xD;
  &#xD;
            -  Evidence of active or latent tuberculosis (TB) as documented by medical history and&#xD;
               examination, and TB testing: a positive (not indeterminate) TB test such as&#xD;
               QuantiFERON-TB Gold Plus test&#xD;
  &#xD;
            -  Positive smoke breathalyzer levels indicative of smoking history at screening and each&#xD;
               in-house admission to the clinical research unit or regular use of tobacco- or&#xD;
               nicotine-containing products (e.g., nicotine patches or vaporizing devices) within 6&#xD;
               months prior to screening.&#xD;
  &#xD;
            -  Estimated glomerular filtration rate (eGFR) of &lt;90 millilitre per minute per 1.73&#xD;
               meter square (mL/min/1.73 m^2) and / or UACR of &gt;30 milligram per gram (mg/g) (&gt;3&#xD;
               milligram per millimoles [mg/mmol]) at screening.&#xD;
  &#xD;
            -  Electrocardiogram (ECG) evidence of ischemic heart disease as determined by the&#xD;
               Investigator.&#xD;
  &#xD;
            -  Positive test for Coronavirus disease 2019 (COVID-19) infection or signs and symptoms&#xD;
               suggestive of COVID-19&#xD;
  &#xD;
            -  Regular excess alcohol consumption within 6 months prior to the study defined as an&#xD;
               average weekly intake of &gt;14 units for males and females&#xD;
  &#xD;
            -  Hypersensitivity to any of the study interventions, or components thereof, or drug or&#xD;
               other allergy that, in the opinion of the investigator or medical monitor,&#xD;
               contraindicates participation in the study Additional exclusions for part 3 cohort&#xD;
               only -&#xD;
  &#xD;
            -  Medical history of NSAIDs hypersensitivities, bronchial asthma, psychiatric and&#xD;
               neurologic disorders, gastrointestinal disorders (including gastroesophageal reflux&#xD;
               disease [GORD], gastritis, peptic ulcer disease and previous GI bleeding), cardiac or&#xD;
               renal disease, coagulation defects and who are not on concomitant medication that may&#xD;
               potentiate the potential harmful effects of indomethacin.&#xD;
  &#xD;
            -  Medical history of diabetes, defined as an HbA1c &gt;5.6%, &gt;39 mmol/mol.&#xD;
  &#xD;
            -  History of severe lactose intolerance or galactosaemia&#xD;
        </textblock>
      </criteria>
      <gender>All</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>
    <overall_contact>
      <last_name>US GSK Clinical Trials Call Center</last_name>
      <phone>877-379-3718</phone>
      <email>GSKClinicalSupportHD@gsk.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>EU GSK Clinical Trials Call Center</last_name>
      <phone>+44 (0) 20 89904466</phone>
      <email>GSKClinicalSupportHD@gsk.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>GSK Investigational Site</name>
        <address>
          <city>Cambridge</city>
          <zip>CB2 0GG</zip>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>US GSK Clinical Trials Call Center</last_name>
        <phone>877-379-3718</phone>
        <email>GSKClinicalSupportHD@gsk.com</email>
      </contact>
      <contact_backup>
        <last_name>EU GSK Clinical Trials Call Centre</last_name>
        <phone>+44 (0) 20 8990 4466</phone>
        <email>GSKClinicalSupportHD@gsk.com</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 11, 2023</study_first_submitted>
    <study_first_submitted_qc>August 11, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 11, 2023</last_update_submitted>
    <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Gastrointestinal (GI)</keyword>
    <keyword>Intestinal permeability</keyword>
    <keyword>First time in human (FTIH)</keyword>
    <keyword>Safety</keyword>
    <keyword>Pharmacokinetics</keyword>
    <keyword>Indomethacin challenge</keyword>
    <keyword>Food effect</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Colitis, Ulcerative</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Indomethacin</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/</ipd_description>
      <ipd_info_type>Study Protocol</ipd_info_type>
      <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
      <ipd_info_type>Informed Consent Form (ICF)</ipd_info_type>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.</ipd_time_frame>
      <ipd_access_criteria>Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.</ipd_access_criteria>
      <ipd_url>https://www.gsk.com/en-gb/innovation/trials/data-transparency/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05999708
  org study id: 218680
  nct id: NCT05999708
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This is a 3-part First Time in Human (FTIH) study to evaluate the safety, tolerability, and
        pharmacokinetics (PK) profile of GSK4381406 following administration of single ascending
        doses (Part 1), repeat ascending doses (Part 2), and repeat doses with an indomethacin
        challenge (Part 3) in healthy adult participants. Part 1 consists of 4 planned cohorts with
        up to 2 treatment periods in each and is expected to have 6 doses (but can accommodate up to
        7 doses). The impact of food on PK of GSK4381406 will also be assessed. Part 2 will
        investigate 14 days of repeat dosing in 3 cohorts with 3 dose levels. Part 3 will evaluate
        the impact of repeat doses of GSK4381406 versus placebo on indomethacin induced changes in
        small intestinal permeability in healthy participants.
  allocation: Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  measure: Part 1 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with adverse events (AEs) and serious adverse events (SAEs)
  time frame: Up to Day 34
  measure: Part 1 - Number of participants with clinically significant changes in hematology laboratory values
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with clinically significant changes in hematology laboratory values
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with clinically significant changes in hematology laboratory values
  time frame: Up to Day 34
  measure: Part 1 - Number of participants with clinically significant changes in chemistry laboratory values
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with clinically significant changes in chemistry laboratory values
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with clinically significant changes in chemistry laboratory values
  time frame: Up to Day 34
  measure: Part 1 - Number of participants with clinically significant changes in urinalysis
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with clinically significant changes in urinalysis
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with clinically significant changes in urinalysis
  time frame: Up to Day 34
  measure: Part 1 - Number of participants with clinically significant changes in vital signs
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with clinically significant changes in vital signs
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with clinically significant changes in vital signs
  time frame: Up to Day 34
  measure: Part 1 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings
  time frame: Up to Day 40
  measure: Part 2 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings
  time frame: Up to Day 54
  measure: Part 3 - Number of participants with clinically significant changes in 12-lead Electrocardiogram (ECG) readings
  time frame: Up to Day 34
  measure: Part 1 - Area under the plasma concentration-time curve (AUC) from time zero to 24-hour post-dose [AUC(0-24)
  time frame: Up to 24 hours post dose
  measure: Part 1 - AUC from time zero to last quantifiable concentration [AUC(0-t)
  time frame: Up to Day 40
  measure: Part 1 - AUC from time zero to infinity [AUC(0-inf)
  time frame: Up to Day 40
  measure: Part 1 - Maximum observed plasma drug concentration (Cmax)
  time frame: Up to Day 40
  measure: Part 1 - Time to maximum observed plasma drug concentration (tmax)
  time frame: Up to Day 40
  measure: Part 1 - Time of last quantifiable concentration (tlast)
  time frame: Up to Day 40
  measure: Part 1 - Apparent terminal phase half-life (t½)
  time frame: Up to Day 40
  measure: Part 2 - AUC from time zero to last quantifiable concentration [AUC(0-t)
  time frame: Day 1 and Day 14
  measure: Part 2 - AUC over the dosing interval [AUC(0-tau)
  time frame: Day 1 and Day 14
  measure: Part 2 - Maximum observed plasma drug concentration (Cmax)
  time frame: Day 1 and Day 14
  measure: Part 2 - Time to maximum observed plasma drug concentration (tmax)
  time frame: Day 1 and Day 14
  measure: Part 2 - AUC from time zero to infinity [AUC(0-inf)
  time frame: Day 14 to Day 54
  measure: Part 2 - Apparent terminal phase half-life (t½)
  time frame: Day 14 to Day 54
  measure: Part 2 - Pre-dose (trough) plasma concentrations (Ctau)
  time frame: Day 1 to Day 14
  measure: Part 2 - Accumulation ratios for Cmax (R)
  time frame: Day 1 and Day 14
  measure: Part 2 - Accumulation ratios for AUC(0-tau) (Ro)
  time frame: Day 1 and Day 14
  measure: Part 1: Cohort 4 - AUC from time zero to infinity [AUC(0-inf)
  time frame: Up to Day 40
  measure: Part 1: Cohort 4 - Maximum observed plasma drug concentration (Cmax)
  time frame: Up to Day 40
  measure: Part 1: Cohort 4 - Time to maximum observed plasma drug concentration (tmax)
  time frame: Up to Day 40
  measure: Part 3 - Lactulose:rhamnose ratio over 0-5 hour in urine
  time frame: At Day 1, 3, 17 and 20
  description: Lactulose and rhamnose concentrations in urine will be collected over 0-2 hour and 2-5 hour, which will be used to derive the ratio over 0-5 hour
  arm group label: Part 1: Cohort 1 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 1 Cohort 1 will receive a single dose of GSK4381406 dose level 1 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 3 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.
  arm group label: Part 1: Cohort 2 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 1 Cohort 2 will receive a single dose of GSK4381406 dose level 2 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 4 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose.
  arm group label: Part 1: Cohort 3 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 1 Cohort 3 will receive a single dose of GSK4381406 dose level 5 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 7 or placebo in Treatment Period 2 in fasted state with washout period of at least 40 days between each dose. Note: Requirement for Treatment Period 2 (dose level 7) will be determined by PK data of previous doses.
  arm group label: Part 1: Cohort 4 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 1 Cohort 4 will receive a single dose of GSK4381406 dose level 6 or placebo in Treatment Period 1 in fasted state, followed by GSK4381406 dose level 6 in Treatment Period 2 in fed state with washout period of at least 40 days between each dose.
  arm group label: Part 2: Cohort 5 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 2 Cohort 5 will receive 14 days of once daily repeat dosing of GSK4381406 dose level A or placebo in fasted state.
  arm group label: Part 2: Cohort 6 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 2 Cohort 6 will receive 14 days of once daily repeat dosing of GSK4381406 dose level B or placebo in fasted state.
  arm group label: Part 2: Cohort 7 - GSK4381406 or placebo
  arm group type: Experimental
  description: Participants in Part 2 Cohort 7 will receive 14 days of once daily repeat dosing of GSK4381406 dose level C or placebo in fasted state.
  arm group label: Part 3 - GSK4381406 or Placebo and Indomethacin
  arm group type: Experimental
  description: Participants in Part 3 will receive 3 days of once daily repeat dosing of GSK4381406 in Treatment Period 1 followed by placebo in Treatment Period 2, or placebo in Treatment Period 1 and GSK4381406 in Treatment Period 2 in a cross-over design with a washout period of at least 14 days between each dosing period. Participants will be dosed in fasted state. The participants will be challenged with indomethacin during the final 2 days of each dosing period.
  intervention type: Drug
  intervention name: GSK4381406
  description: GSK4381406 will be administered.
  arm group label: Part 1: Cohort 1 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 2 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 3 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 4 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 5 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 6 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 7 - GSK4381406 or placebo
  arm group label: Part 3 - GSK4381406 or Placebo and Indomethacin
  intervention type: Drug
  intervention name: Placebo
  description: Placebo will be administered.
  arm group label: Part 1: Cohort 1 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 2 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 3 - GSK4381406 or placebo
  arm group label: Part 1: Cohort 4 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 5 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 6 - GSK4381406 or placebo
  arm group label: Part 2: Cohort 7 - GSK4381406 or placebo
  arm group label: Part 3 - GSK4381406 or Placebo and Indomethacin
  intervention type: Drug
  intervention name: Indomethacin
  description: Indomethacin will be administered.
  arm group label: Part 3 - GSK4381406 or Placebo and Indomethacin
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 55 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: GSK Clinical Trials
  role: Study Director
  affiliation: GlaxoSmithKline
  last name: US GSK Clinical Trials Call Center
  phone: 877-379-3718
  email: GSKClinicalSupportHD@gsk.com
  last name: EU GSK Clinical Trials Call Center
  phone: +44 (0) 20 89904466
  email: GSKClinicalSupportHD@gsk.com
  facility: 
  contact: 
  contact backup: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Colitis, Ulcerative
  mesh term: Indomethacin
  sharing ipd: Yes
  ipd description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
  ipd info type: Study Protocol
  ipd info type: Statistical Analysis Plan (SAP)
  ipd info type: Informed Consent Form (ICF)
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
  ipd access criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
  ipd url: https://www.gsk.com/en-gb/innovation/trials/data-transparency/