<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/NCT04504435</url>
  </required_header>
  <id_info>
    <org_study_id>208441</org_study_id>
    <secondary_id>2019-004492-39</secondary_id>
    <nct_id>NCT04504435</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability and Pharmacokinetics (PK) Investigation of GSK3494245 in Healthy Participants</brief_title>
  <official_title>A Randomized, Double-blind, Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single (in Both Fed and Fasted States) Doses of GSK3494245 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH)&#xD;
      study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study&#xD;
      will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of&#xD;
      a single ascending dose (SAD), crossover design where each participant will receive a maximum&#xD;
      of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each&#xD;
      dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period,&#xD;
      according to the randomization schedule in a blinded manner. Cohort 3 will comprise of a&#xD;
      2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1&#xD;
      regimen under fed then fasted conditions in a 1:1 ratio. The fed conditions will investigate&#xD;
      the effect of safety, tolerability and PK of a single dose of GSK3494245 following food&#xD;
      administration.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 29, 2020</start_date>
  <completion_date type="Anticipated">June 14, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 14, 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>
    <intervention_model_description>The study will consist of 3 cohorts (Cohorts 1, 2 and 3), conducted in sequential order. Cohorts 1 and 2 will consist of a single dose, ascending, crossover design. Cohorts 1-2 will comprise of a 4-way crossover which includes 4 dosing regimens under fasted conditions. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed condition and 1 regimen under fed then fasted condition in a 1:1 ratio.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This will be a double-blind study with respect to allocation of GSK3494245 or placebo to participants. The food effect part of the study will be open label.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with treatment emergent AEs and SAEs</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant abnormal findings in hematology parameters</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Blood samples will be collected for the assessment of hematology parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant abnormal findings in clinical chemistry parameters</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Blood samples will be collected for the assessment of chemistry parameters</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with urinalysis findings</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Urine samples will be collected for the assessment of urinalysis parameters.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant abnormal findings in vital signs</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Number of participants with abnormal vital signs will be assessed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters</measure>
    <time_frame>Up to 14 days post last dose in each treatment period</time_frame>
    <description>Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal cardiac telemetry findings</measure>
    <time_frame>Up to 24 hours post dose on Day 1</time_frame>
    <description>Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-t) of GSK3494245 following single dose administration under fed condition</measure>
    <time_frame>Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC (0-inf) of GSK3494245 following single dose administration under fed condition</measure>
    <time_frame>Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of GSK3494245 following single dose administration under fed condition</measure>
    <time_frame>Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax of GSK3494245 following single dose administration under fed condition</measure>
    <time_frame>Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 of GSK3494245 following single dose administration under fed condition</measure>
    <time_frame>Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal Clearance (CLr) of GSK3494245 following single dose administration</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dose-proportionality assessment using Cmax following single dose of GSK3494245</measure>
    <time_frame>Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)</time_frame>
    <description>Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">54</enrollment>
  <condition>Leishmaniasis</condition>
  <arm_group>
    <arm_group_label>Participants in Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Participants in Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: Participants receiving GSK3494245 (fasted then fed)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the selected dose level (DLX) of GSK3494245 in the fasted state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fed state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3: Participants receiving GSK3494245 (fed then fasted)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive the DLX of GSK3494245 in the fed state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fasted state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK3494245</intervention_name>
    <description>Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.</description>
    <arm_group_label>Cohort 3: Participants receiving GSK3494245 (fasted then fed)</arm_group_label>
    <arm_group_label>Cohort 3: Participants receiving GSK3494245 (fed then fasted)</arm_group_label>
    <arm_group_label>Participants in Cohort 1</arm_group_label>
    <arm_group_label>Participants in Cohort 2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo capsules will be provided</description>
    <arm_group_label>Participants in Cohort 1</arm_group_label>
    <arm_group_label>Participants in Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Participant must be 18 to &lt;=50 years of age, at the time of signing the informed&#xD;
             consent.&#xD;
&#xD;
          -  Participant must be healthy as determined by the Investigator or medically qualified&#xD;
             designee based on a medical evaluation including medical history, physical&#xD;
             examination, laboratory tests and cardiac monitoring. A participant with a clinical&#xD;
             abnormality or laboratory parameter(s) which is/are not specifically listed in the&#xD;
             inclusion or exclusion criteria, outside the normal reference range for the population&#xD;
             being studied may be included only if the Investigator in consultation with the&#xD;
             Medical Monitor (if required) agree and document that the finding is unlikely to&#xD;
             introduce additional risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Body weight &gt;=50 Kilograms (kg) and body mass index (BMI) within the range 18.5-28&#xD;
             Kilograms per meter square (kg/m^2) (inclusive).&#xD;
&#xD;
          -  Male participants only. A male participant with a female partner of reproductive&#xD;
             potential must agree to use contraception during the intervention period and for at&#xD;
             least 90 days after the last dose of study treatment and refrain from donating sperm&#xD;
             during this period.&#xD;
&#xD;
          -  Capable of giving signed informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the Informed consent form (ICF) and protocol.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal,&#xD;
             endocrine, hematological, or neurological disorders capable of significantly altering&#xD;
             the absorption, metabolism, or elimination of drugs; constituting a risk when taking&#xD;
             the study treatment; or interfering with the interpretation of data.&#xD;
&#xD;
          -  Abnormal blood pressure, as determined by the investigator.&#xD;
&#xD;
          -  Previous history of leishmaniasis.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) greater than 1.5 times upper limit of normal (ULN).&#xD;
&#xD;
          -  Total bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times&#xD;
             ULN is acceptable if total bilirubin is fractionated and direct bilirubin less than 35&#xD;
             percent [%]).&#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;
          -  Current or history of clinically significant gastritis or gastroduodenal ulcers or&#xD;
             regular use of non-steroidal anti-inflammatory drugs (NSAID).&#xD;
&#xD;
          -  Consumption of greater than 14 units/week alcohol (male volunteers).&#xD;
&#xD;
          -  Current or history of change in taste or smell without any plausible clinical&#xD;
             explanation based on investigator's clinical judgement.&#xD;
&#xD;
          -  QTc greater than 450 milliseconds (msec) based on average of triplicate ECGs.&#xD;
&#xD;
          -  Waveform abnormalities including premature ventricular contraction (PVC) triplets and&#xD;
             more than 500 single PVCs in 24 hours, or any other abnormalities at the discretion of&#xD;
             investigator.&#xD;
&#xD;
          -  Medical history of cardiac arrhythmias or cardiac disease or a family or personal&#xD;
             history of long QT syndrome.&#xD;
&#xD;
          -  Past or intended use of over-the-counter or prescription medication, including herbal&#xD;
             medications, NSAIDs, proton pump inhibitors (PPIs) or anti-histamine 2 receptor (H2)&#xD;
             antagonists within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5&#xD;
             half-lives (whichever is the longest) prior to dosing. Other concomitant medication&#xD;
             may be considered on a case by case basis by the investigator in consultation with the&#xD;
             medical monitor. Paracetamol is permitted (capped to &lt;=2 grams/day).&#xD;
&#xD;
          -  Participation in the study that would result in loss of blood or blood products in&#xD;
             excess of 500 milliliter (mL) within a 56-day period.&#xD;
&#xD;
          -  Exposure to more than 4 new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Current enrollment or past participation within the last 30 days before signing of&#xD;
             consent in any other clinical study involving an investigational study intervention or&#xD;
             any other type of medical research.&#xD;
&#xD;
          -  Current enrollment or past participation in this clinical study.&#xD;
&#xD;
          -  Participants with renal function defined as Chronic Kidney Disease Epidemiology&#xD;
             Collaboration (CKD-EPI) with an age appropriate Glomerular filtration rate (GFR) &lt;90&#xD;
             (milliliter per minute per 1.73 meter square [mL/min/1.73m^2]).&#xD;
&#xD;
          -  Screening urine albumin:creatinine ratio &gt;30 milligram per gram (mg/g) (&gt;3 milligram&#xD;
             per millimole [mg/mmol])&#xD;
&#xD;
          -  Presence of hepatitis B surface antigen (HBsAg) test result at screening.&#xD;
&#xD;
          -  Positive hepatitis C antibody test result at screening.&#xD;
&#xD;
          -  Positive hepatitis C Ribonucleic acid (RNA) test result at screening.&#xD;
&#xD;
          -  Positive human immunodeficiency virus (HIV) antibody test.&#xD;
&#xD;
          -  Presence of clinically significant hematuria and/or proteinuria.&#xD;
&#xD;
          -  Carbon monoxide levels indicative of smoking or history or regular use of tobacco or&#xD;
             nicotine-containing products within 3 months prior to screening.&#xD;
&#xD;
          -  Positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  Regular use of known drugs of abuse.&#xD;
&#xD;
          -  Food Effect Cohort 3 only: Participant must have no dietary restrictions (e.g.,&#xD;
             lactose intolerance) or inability to eat gelatin or an adapted standard meal (includes&#xD;
             35-40% fat content).&#xD;
&#xD;
          -  Food Effect Cohort 3 only: History of gall bladder surgery or gall bladder removal, or&#xD;
             history of an acute disease state (e.g. cholelithiasis) within 14 days prior to&#xD;
             receiving the study treatment.&#xD;
&#xD;
          -  Participants must not have travelled to an area (as determined by the investigator)&#xD;
             with a high prevalence of leishmanial/parasitic infections in the 6 months before&#xD;
             screening or intend to do so in the 3 months after the final dose of study treatment.&#xD;
&#xD;
          -  Sensitivity to any of the study treatments, or components thereof, or drug or other&#xD;
             allergy that, in the opinion of the Investigator or GSK Medical Monitor,&#xD;
             contraindicates participation in the study.&#xD;
&#xD;
          -  A positive laboratory confirmation of corona virus disease 2019 (COVID-19) infection,&#xD;
             or high clinical index of suspicion for COVID-19.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <gender_description>A male participant with a female partner of reproductive potential must agree to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.</gender_description>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 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 2GG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <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 5, 2020</study_first_submitted>
  <study_first_submitted_qc>August 5, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2020</study_first_posted>
  <last_update_submitted>August 4, 2023</last_update_submitted>
  <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GSK3494245</keyword>
  <keyword>Leishmaniasis</keyword>
  <keyword>Single Ascending Dose</keyword>
  <keyword>First Time in Human</keyword>
  <keyword>Pharmacokinetics</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Leishmaniasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>IPD for this study will be made available via the Clinical Study Data Request site.</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>IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.</ipd_time_frame>
    <ipd_access_criteria>Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.</ipd_access_criteria>
    <ipd_url>http://clinicalstudydatarequest.com</ipd_url>
  </patient_data>
  <!-- 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/NCT04504435
org study id: 208441
secondary id: 2019-004492-39
nct id: NCT04504435
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a Phase 1, double-blind, randomized, placebo-controlled, first time in human (FTIH)
      study to assess the safety, tolerability and PK of a single dose of GSK3494245. The study
      will consist of 3 cohorts, conducted in a sequential manner. Cohorts 1 and 2 will consist of
      a single ascending dose (SAD), crossover design where each participant will receive a maximum
      of 3 ascending oral doses of GSK3494245 and 1 placebo dose under fasted conditions. At each
      dose level, GSK3494245 and placebo will be administered in a 3:1 ratio, within each period,
      according to the randomization schedule in a blinded manner. Cohort 3 will comprise of a
      2-way crossover which includes 1 dosing regimen under fasted then fed conditions and 1
      regimen under fed then fasted conditions in a 1:1 ratio. The fed conditions will investigate
      the effect of safety, tolerability and PK of a single dose of GSK3494245 following food
      administration.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: The study will consist of 3 cohorts (Cohorts 1, 2 and 3), conducted in sequential order. Cohorts 1 and 2 will consist of a single dose, ascending, crossover design. Cohorts 1-2 will comprise of a 4-way crossover which includes 4 dosing regimens under fasted conditions. Cohort 3 will comprise of a 2-way crossover which includes 1 dosing regimen under fasted then fed condition and 1 regimen under fed then fasted condition in a 1:1 ratio.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: This will be a double-blind study with respect to allocation of GSK3494245 or placebo to participants. The food effect part of the study will be open label.
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
time frame: Up to 14 days post last dose in each treatment period
description: An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. SAE is defined as any untoward medical occurrence that, at any dose: results in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment.
measure: Number of participants with treatment emergent AEs and SAEs
time frame: Up to 14 days post last dose in each treatment period
description: Treatment emergent AE and SAE are any untoward medical occurrences in a clinical study participant, having causal relation with the use of a study intervention.
measure: Number of participants with clinically significant abnormal findings in hematology parameters
time frame: Up to 14 days post last dose in each treatment period
description: Blood samples will be collected for the assessment of hematology parameters.
measure: Number of participants with clinically significant abnormal findings in clinical chemistry parameters
time frame: Up to 14 days post last dose in each treatment period
description: Blood samples will be collected for the assessment of chemistry parameters
measure: Number of participants with urinalysis findings
time frame: Up to 14 days post last dose in each treatment period
description: Urine samples will be collected for the assessment of urinalysis parameters.
measure: Number of participants with clinically significant abnormal findings in vital signs
time frame: Up to 14 days post last dose in each treatment period
description: Number of participants with abnormal vital signs will be assessed.
measure: Number of participants with clinically significant abnormal findings in Electrocardiogram (ECG) Parameters
time frame: Up to 14 days post last dose in each treatment period
description: Triplicate 12-lead ECGs will be obtained using an ECG machine that automatically calculates the heart rate and measures PR interval, QRS interval, QT interval, Corrected QT (QTc) interval.
measure: Number of participants with abnormal cardiac telemetry findings
time frame: Up to 24 hours post dose on Day 1
description: Telemetry is the continuous monitoring of a participants heart rate and rhythm from a remote location. Continuous cardiac telemetry will start in a supine position after at least 5 minutes rest.
measure: Area under the plasma drug concentration (AUC) versus time curve (AUC[0-t]) of GSK3494245 following single dose administration under fasting condition
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 minutes [min], 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fasting condition.
measure: AUC (0-t) of GSK3494245 following single dose administration under fed condition
time frame: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate AUC (0-t) of GSK3494245 under fed condition.
measure: AUC-time curve from time zero to extrapolated to infinity (AUC[0-inf]) of GSK3494245 following single dose administration under fasting condition
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate AUC (0-inf) of GSK3494245 under fasting condition.
measure: AUC (0-inf) of GSK3494245 following single dose administration under fed condition
time frame: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245 under fed condition.
measure: Maximum observed plasma drug concentration (Cmax) of GSK3494245 following single dose administration under fasting condition
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fasting condition.
measure: Cmax of GSK3494245 following single dose administration under fed condition
time frame: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245 under fed condition.
measure: Time to maximum observed plasma drug concentration (Tmax) of GSK3494245 following single dose administration under fasting condition
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fasting condition.
measure: Tmax of GSK3494245 following single dose administration under fed condition
time frame: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate Tmax of GSK3494245 under fed condition.
measure: Apparent terminal half-life (t1/2) of GSK3494245 following single dose administration under fasting condition
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
measure: t1/2 of GSK3494245 following single dose administration under fed condition
time frame: Cohort 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate t1/2 of GSK3494245.
measure: Amount of GSK3494245 excreted in urine over 24 hours (Ae0-24h) following single dose administration
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Urine samples will be collected at the indicated time points to evaluate Ae0-24h of GSK3494245.
measure: Fraction of dose excreted in urine over 24 hours (fe%) of GSK3494245 following single dose administration
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Urine samples will be collected at the indicated time points to evaluate fe% of GSK3494245
measure: Renal Clearance (CLr) of GSK3494245 following single dose administration
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Urine samples will be collected at the indicated time points to evaluate CLr of GSK3494245.
measure: Dose-proportionality assessment using AUC(0-inf) following single dose of GSK3494245
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate AUC(0-inf) of GSK3494245.
measure: Dose-proportionality assessment using Cmax following single dose of GSK3494245
time frame: Cohort 1, 2 and 3: Day 1 (Pre-dose, 10 min, 30 min, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12 and 24 hour post dose in each treatment period)
description: Blood samples will be collected at the indicated time points to evaluate Cmax of GSK3494245.
arm group label: Participants in Cohort 1
arm group type: Experimental
description: Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with 20 milligram (mg) and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
arm group label: Participants in Cohort 2
arm group type: Experimental
description: Participants will receive a maximum of 3 ascending dose levels of GSK3494245 starting with dose level (DL) 5 and 1 placebo dose orally on Day 1 of each treatment period under fasted conditions. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
arm group label: Cohort 3: Participants receiving GSK3494245 (fasted then fed)
arm group type: Experimental
description: Participants will receive the selected dose level (DLX) of GSK3494245 in the fasted state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fed state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
arm group label: Cohort 3: Participants receiving GSK3494245 (fed then fasted)
arm group type: Experimental
description: Participants will receive the DLX of GSK3494245 in the fed state on Day 1 in Period 1 followed by a single dose of GSK3494245 in the fasted state in Period 2. There will be a washout period of at least 48 hours or 5-half-lives (whichever is longer) between each dose for an individual participant.
intervention type: Drug
intervention name: GSK3494245
description: Capsule of 10-250 mg dose strength will be provided in labelled High Density Polyethylene (HDPE) bottles.
arm group label: Cohort 3: Participants receiving GSK3494245 (fasted then fed)
arm group label: Cohort 3: Participants receiving GSK3494245 (fed then fasted)
arm group label: Participants in Cohort 1
arm group label: Participants in Cohort 2
intervention type: Drug
intervention name: Placebo
description: Matching placebo capsules will be provided
arm group label: Participants in Cohort 1
arm group label: Participants in Cohort 2
criteria: 
gender: Male
gender based: Yes
gender description: A male participant with a female partner of reproductive potential must agree to use contraception during the intervention period and for at least 90 days after the last dose of study treatment and refrain from donating sperm during this period.
minimum age: 18 Years
maximum age: 50 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: 
status: Recruiting
contact: 
contact backup: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Leishmaniasis
sharing ipd: Yes
ipd description: IPD for this study will be made available via the Clinical Study Data Request site.
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: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
ipd access criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.
ipd url: http://clinicalstudydatarequest.com