<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/NCT04472897</url>
  </required_header>
  <id_info>
    <org_study_id>210035</org_study_id>
    <nct_id>NCT04472897</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety, Tolerability and Pharmacokinetics of GSK2556286 in Healthy Adult Participants</brief_title>
  <official_title>A Randomised, Double Blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Oral Doses and the Food Effect of GSK2556286 in Healthy Adult 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 first time in human (FTIH) study to evaluate the safety, tolerability and&#xD;
      pharmacokinetics (PK) of single and repeat ascending doses of GSK2556286 in healthy adult&#xD;
      participants. Food effect (FE) cohorts will investigate the influence of food on the PK of&#xD;
      GSK2556286. The study will be conducted in two parts. Part A will be a single ascending dose&#xD;
      (SAD) including up to 11 cohorts (Cohort 1A to cohort 11A) and Part B will be a multiple&#xD;
      ascending dose (MAD), including up to 4 cohorts (Cohort 1B to cohort 4B).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">October 30, 2020</start_date>
  <completion_date type="Anticipated">December 15, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 15, 2023</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>This is a double-blind, randomized, sequential, parallel dose cohort study.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
    <masking_description>This is a double-blind study.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs</measure>
    <time_frame>Up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Number of participants with any SAEs and non-SAEs</measure>
    <time_frame>Up to Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Number of participants with AEs (SAEs and non-SAEs) by severity</measure>
    <time_frame>Up to Day 15</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Number of participants with AEs (SAEs and non-SAEs) by severity</measure>
    <time_frame>Up to Day 28</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Plasma concentrations of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Area under the plasma drug concentration versus time curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Maximum observed plasma drug concentration (Cmax) of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part A: Apparent terminal half-life (T1/2) of GSK2556286</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Plasma concentrations of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose. Day 12 and 13: Pre-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: AUC(0-t) of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: AUC(0-inf) of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Area under the plasma drug concentration versus time curve from time zero during a dosage interval of time tau (AUC[0-tau)] of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Cmax of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Tmax of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: Trough plasma concentration (Ctau) of GSK2556286</measure>
    <time_frame>Pre-dose on Days 1, 12, 13 and 14</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Part B: T1/2 of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Cmax of GSK2556286 under fasted and fed conditions</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Tmax of GSK2556286 under fasted and fed conditions</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: T1/2 of GSK2556286 under fasted and fed conditions</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose proportionality of GSK2556286 based on AUC(0-inf)</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose proportionality of GSK2556286 based on AUC(0-t)</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part A: Dose proportionality of GSK2556286 based on Cmax</measure>
    <time_frame>Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dose proportionality of GSK2556286 based on AUC(0-tau)</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Dose proportionality of GSK2556286 based on Cmax</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro])</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax)</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Steady state ratio (Rss) of GSK2556286</measure>
    <time_frame>Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Part B: Ctau at the end of the dosing interval to assess steady state of GSK2556286</measure>
    <time_frame>Pre-dose on Days 1, 12, 13 and 14</time_frame>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Tuberculosis</condition>
  <arm_group>
    <arm_group_label>Part A: Participants receiving GSK2556286</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to receive GSK2556286 in any of the 11 cohorts. In each dosing cohort, 6 participants will receive a single dose of GSK2556286. Following initial dosing of cohorts in the fasted state, one cohort will investigate the effect of food administration (high fat meal) on safety, tolerability and PK data of GSK2556286. One cohort may also investigate the effects of a moderate fat meal.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Participants receiving placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be randomized to receive matching placebo in any of the 11 cohorts. In each dosing cohort, 2 participants will receive a single dose of matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Participants receiving GSK2556286</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will be randomized to receive GSK2556286 in any of the 4 cohorts. In each dosing cohort, 6 participants will receive repeat doses of GSK2556286 under either fasting or fed conditions, dependent on the results from Part A.&#xD;
Appropriate doses and dose regimens for Part B will be selected by the Dose Escalation Committee based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Participants receiving placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will be randomized to receive matching placebo in any of the 4 cohorts. In each dosing cohort, 2 participants will receive repeat doses of matching placebo under either fasting or fed conditions, dependent on the results from Part A.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2556286</intervention_name>
    <description>GSK2556286 will be administered.</description>
    <arm_group_label>Part A: Participants receiving GSK2556286</arm_group_label>
    <arm_group_label>Part B: Participants receiving GSK2556286</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 A: Participants receiving placebo</arm_group_label>
    <arm_group_label>Part B: Participants receiving placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Participant must be 18 to 60 years of age inclusive, at the time of signing the&#xD;
             informed consent. Participants aged 51 to 60 years must have received at least one&#xD;
             dose of Coronavirus disease-2019 (COVID-19) vaccine approved by the local regulatory&#xD;
             authority at least 3 weeks prior to signing the consent form.&#xD;
&#xD;
          -  Participants who are overtly healthy as determined by medical evaluation including&#xD;
             medical history, physical examination, laboratory tests, and cardiac monitoring. A&#xD;
             participant with a clinical abnormality or laboratory parameter(s) which is/are not&#xD;
             specifically listed in the inclusion or exclusion criteria, outside the normal&#xD;
             reference range for the population being studied may be included only if the&#xD;
             Investigator considers and documents that the finding is unlikely to introduce&#xD;
             additional risk factors and will not interfere with the study procedures.&#xD;
&#xD;
          -  Body weight more than or equal to (&gt;=)50 kilograms (kg) and body mass index (BMI)&#xD;
             within the range 19 to 29.9 kilograms per meter square (kg/m^2) inclusive.&#xD;
&#xD;
          -  Male and/or Female Participants. A male participant with a female partner of&#xD;
             reproductive potential must agree to use contraception of this clinical study protocol&#xD;
             during the treatment period and for at least 90 days after the last dose of study&#xD;
             treatment and refrain from donating sperm during this period. A female participant is&#xD;
             eligible to participate if she is not a woman of childbearing potential (WONCBP).&#xD;
&#xD;
          -  The participant is able to understand and comply with protocol requirements,&#xD;
             instructions and protocol-stated restrictions.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Significant history of or current, cardiovascular, respiratory (including asthma),&#xD;
             hepatic, renal, gastrointestinal, endocrine, hematological, infectious or neurological&#xD;
             disorders capable of significantly altering the absorption, metabolism, or elimination&#xD;
             of drugs: constituting a risk when taking part in the study or interfering with the&#xD;
             interpretation of data.&#xD;
&#xD;
          -  Alanine aminotransferase (ALT) greater than (&gt;)1.5 times upper limit of normal (ULN).&#xD;
&#xD;
          -  Total bilirubin &gt;1.5 times ULN (isolated total bilirubin &gt;1.5 times ULN may be&#xD;
             acceptable, after consultation with the GlaxoSmithKline (GSK) Medical Monitor, if&#xD;
             total bilirubin is fractionated and direct bilirubin less than [&lt;]35 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) or&#xD;
             cholecystectomy.&#xD;
&#xD;
          -  Current or past history of significant renal disease including renal stones.&#xD;
&#xD;
          -  Current or past history of gastroduodenal ulcers or persistent gastritis requiring&#xD;
             medication.&#xD;
&#xD;
          -  Medical history of cardiac arrhythmias or cardiac disease or a family or personal&#xD;
             history of long QT syndrome.&#xD;
&#xD;
          -  Exclusion criteria for screening electrocardiogram (ECG) with:&#xD;
&#xD;
               1. Heart rate of &lt;40 or &gt;100 beats per minute (bpm) in males and &lt;50 or &gt;100 bpm in&#xD;
                  females.&#xD;
&#xD;
               2. PR interval of &lt;120 or &gt;220 milliseconds (msec) in males and females.&#xD;
&#xD;
               3. QRS duration of &lt;70 or &gt;120 msec in males and females.&#xD;
&#xD;
               4. Electrocardiogram QT interval corrected for heart rate using Fridericia's formula&#xD;
                  (QTcF) interval of &gt;450 msec in males and females.&#xD;
&#xD;
          -  Evidence of previous myocardial infarction (does not include ST segment changes&#xD;
             associated with re-polarization).&#xD;
&#xD;
          -  Any clinically significant conduction abnormality (including but not specific to left&#xD;
             or right complete bundle branch block, atrioventricular [AV] block [second degree or&#xD;
             higher], Wolff -Parkinson-White [WPW] syndrome).&#xD;
&#xD;
          -  Sinus Pauses &gt;3 seconds.&#xD;
&#xD;
          -  Any significant arrhythmia which, in the opinion of the Investigator or GSK Medical&#xD;
             monitor, will interfere with the safety for the individual participant.&#xD;
&#xD;
          -  Non-sustained or sustained ventricular tachycardia (3 consecutive ventricular ectopic&#xD;
             beats).&#xD;
&#xD;
          -  Evidence of latent tuberculosis documented by:&#xD;
&#xD;
               1. medical history and examination.&#xD;
&#xD;
               2. Tuberculosis (TB) testing : either a positive tuberculin skin test (TST) (defined&#xD;
                  as a skin induration &gt;5 millimeters [mm] at 48 to 72 hours, regardless of&#xD;
                  Bacillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not&#xD;
                  indeterminate) TB test such as QuantiFERON-TB Gold Plus test. In cases where the&#xD;
                  QuantiFERON or TST is indeterminate, the participant may have the test repeated&#xD;
                  once, but they will not be eligible for the study unless the second test is&#xD;
                  negative. In cases where the QuantiFERON or TST test is positive, the participant&#xD;
                  should be followed up as per standard of care.&#xD;
&#xD;
          -  Use of prescription or non-prescription drugs, including Nonsteroidal&#xD;
             anti-inflammatory drugs (NSAIDs), high-dose vitamins, herbal and dietary supplements&#xD;
             (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme&#xD;
             inducer) or 5 half-lives (whichever is longer) prior to the first dose of study&#xD;
             medication.&#xD;
&#xD;
          -  Cotinine in urine indicative of smoking or history or regular use of tobacco or&#xD;
             nicotine-containing products within 3 months.&#xD;
&#xD;
          -  Current regular alcohol consumption defined as an average weekly intake of &gt;21 units&#xD;
             for males or &gt;14 units for females. One unit is equivalent to 8 grams (g) of alcohol:&#xD;
             a half-pint (approximately 240 milliliters [mL]) of beer, 1 glass (125 mL) of wine or&#xD;
             1 (25 mL) measure of spirits.&#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.&#xD;
&#xD;
          -  A positive test for Human immunodeficiency virus (HIV) antibody.&#xD;
&#xD;
          -  Urinary analysis indicating presence of blood, protein or glucose. If trace or 1 plus&#xD;
             (+) is found on urine dipstick, a repeat test can be performed. If repeat is positive,&#xD;
             participant is excluded from recruitment.&#xD;
&#xD;
          -  Screening age-appropriate estimated glomerular filtration rate (eGFR) &lt;90 milliliters&#xD;
             per minute mL/min as assessed by the Chronic Kidney Disease Epidemiology Collaboration&#xD;
             (CKD-EPI) equation.&#xD;
&#xD;
          -  Serum (and in the MAD, urinary) electrolytes outside of normal range. May be repeated&#xD;
             once if abnormal.&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen.&#xD;
&#xD;
          -  The participant has taken part 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: 90 days, 5 half-lives or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer).&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day.&#xD;
&#xD;
          -  Part A (Food Effect) Cohort: Participant must have no relevant dietary restrictions&#xD;
             (lactose intolerance) or inability to eat a high fat meal.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 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>Groningen</city>
        <zip>9713 AG</zip>
        <country>Netherlands</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <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>
    <investigator>
      <last_name>Edward Banham-Hall</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>July 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 14, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>January 22, 2023</last_update_submitted>
  <last_update_submitted_qc>January 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>GSK2556286</keyword>
  <keyword>Pharmacokinetics</keyword>
  <keyword>Interventional</keyword>
  <keyword>Tuberculosis</keyword>
  <keyword>Placebo-controlled</keyword>
  <keyword>FTIH</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tuberculosis</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 of the study, a 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/NCT04472897
org study id: 210035
nct id: NCT04472897
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a first time in human (FTIH) study to evaluate the safety, tolerability and
      pharmacokinetics (PK) of single and repeat ascending doses of GSK2556286 in healthy adult
      participants. Food effect (FE) cohorts will investigate the influence of food on the PK of
      GSK2556286. The study will be conducted in two parts. Part A will be a single ascending dose
      (SAD) including up to 11 cohorts (Cohort 1A to cohort 11A) and Part B will be a multiple
      ascending dose (MAD), including up to 4 cohorts (Cohort 1B to cohort 4B).
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: This is a double-blind, randomized, sequential, parallel dose cohort study.
primary purpose: Treatment
masking: Double (Participant, Investigator)
masking description: This is a double-blind study.
measure: Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs
time frame: Up to Day 15
measure: Part B: Number of participants with any SAEs and non-SAEs
time frame: Up to Day 28
measure: Part A: Number of participants with AEs (SAEs and non-SAEs) by severity
time frame: Up to Day 15
measure: Part B: Number of participants with AEs (SAEs and non-SAEs) by severity
time frame: Up to Day 28
measure: Part A: Plasma concentrations of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Area under the plasma drug concentration versus time curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Maximum observed plasma drug concentration (Cmax) of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Apparent terminal half-life (T1/2) of GSK2556286
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Plasma concentrations of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose. Day 12 and 13: Pre-dose
measure: Part B: AUC(0-t) of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: AUC(0-inf) of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Area under the plasma drug concentration versus time curve from time zero during a dosage interval of time tau (AUC[0-tau)] of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Cmax of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Tmax of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Trough plasma concentration (Ctau) of GSK2556286
time frame: Pre-dose on Days 1, 12, 13 and 14
measure: Part B: T1/2 of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Cmax of GSK2556286 under fasted and fed conditions
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Tmax of GSK2556286 under fasted and fed conditions
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: T1/2 of GSK2556286 under fasted and fed conditions
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Dose proportionality of GSK2556286 based on AUC(0-inf)
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Dose proportionality of GSK2556286 based on AUC(0-t)
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part A: Dose proportionality of GSK2556286 based on Cmax
time frame: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Dose proportionality of GSK2556286 based on AUC(0-tau)
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Dose proportionality of GSK2556286 based on Cmax
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro])
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax)
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Steady state ratio (Rss) of GSK2556286
time frame: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
measure: Part B: Ctau at the end of the dosing interval to assess steady state of GSK2556286
time frame: Pre-dose on Days 1, 12, 13 and 14
arm group label: Part A: Participants receiving GSK2556286
arm group type: Experimental
description: Participants will be randomized to receive GSK2556286 in any of the 11 cohorts. In each dosing cohort, 6 participants will receive a single dose of GSK2556286. Following initial dosing of cohorts in the fasted state, one cohort will investigate the effect of food administration (high fat meal) on safety, tolerability and PK data of GSK2556286. One cohort may also investigate the effects of a moderate fat meal.
arm group label: Part A: Participants receiving placebo
arm group type: Placebo Comparator
description: Participants will be randomized to receive matching placebo in any of the 11 cohorts. In each dosing cohort, 2 participants will receive a single dose of matching placebo.
arm group label: Part B: Participants receiving GSK2556286
arm group type: Experimental
description: Participants will be randomized to receive GSK2556286 in any of the 4 cohorts. In each dosing cohort, 6 participants will receive repeat doses of GSK2556286 under either fasting or fed conditions, dependent on the results from Part A.
Appropriate doses and dose regimens for Part B will be selected by the Dose Escalation Committee based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B.
arm group label: Part B: Participants receiving placebo
arm group type: Placebo Comparator
description: Participants will be randomized to receive matching placebo in any of the 4 cohorts. In each dosing cohort, 2 participants will receive repeat doses of matching placebo under either fasting or fed conditions, dependent on the results from Part A.
intervention type: Drug
intervention name: GSK2556286
description: GSK2556286 will be administered.
arm group label: Part A: Participants receiving GSK2556286
arm group label: Part B: Participants receiving GSK2556286
intervention type: Drug
intervention name: Placebo
description: Placebo will be administered
arm group label: Part A: Participants receiving placebo
arm group label: Part B: Participants receiving placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 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: Completed
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
country: Netherlands
country: United Kingdom
responsible party type: Sponsor
mesh term: Tuberculosis
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 of the study, a 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