<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/NCT01687309</url>
  </required_header>
  <id_info>
    <org_study_id>116439</org_study_id>
    <nct_id>NCT01687309</nct_id>
  </id_info>
  <brief_title>A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Repeat Doses of GSK2586184 and the Effect of Food and Gender</brief_title>
  <acronym>JAK116439</acronym>
  <official_title>A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2586184 Following a Single Doseof 800mg and Repeat Oral Tablet Doses of 800mg b.d and the Effect of Food and Gender on the Pharmacokinetics of oralGSK2586184 in Healthy Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of&#xD;
      single and repeat doses of 800 mg GSK2586184 in healthy subjects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a study in healthy volunteers to investigate the safety, tolerability,&#xD;
      pharmacokinetics (the body's effect on the drug) and pharmacodynamics (the drug's effect on&#xD;
      the body) of single and repeat doses of 800 mg GSK2586184. The effect of food and gender on&#xD;
      pharmacokinetics will also be investigated following single dosing.&#xD;
&#xD;
      The study is made up of 2 groups of healthy subjects. The first group consists of 6 female&#xD;
      subjects who will receive a single dose of 800mg GSK2586184 (study medication) during 2&#xD;
      seperate sessions. One session will involve the female subjects taking the study medication&#xD;
      with food and the other session will involve study medication being taken without food. The&#xD;
      safety and tolerability of the study medication in female subjects and the effect of food on&#xD;
      the pharmacokinetics of the study medication will be investigated.&#xD;
&#xD;
      The second group will consist of 12 healthy male subjects participating in 2 sessions. 8&#xD;
      subjects will receive study medication and 4 will receive placebo (dummy medication) during&#xD;
      the course of the study. Neither they or their study doctor will know which one they are&#xD;
      given. Each male subject will receive a single dose of study medication or placebo followed&#xD;
      by 13 days of twice daily dosing of study medication or placebo. Each dose will be taken with&#xD;
      food.The single dose results from this group of subjects will be compared to the female group&#xD;
      to investigate the effect of gender on pharmacokinetics. The safety and pharmacokinetics of&#xD;
      repeat dosing will be investigated. The effect of repeat dosing on kidney function and the&#xD;
      immune system will also be investigated.&#xD;
&#xD;
      The study will take place in the SGS Clinical Pharmacology Unit in Antwerp, Belgium. A&#xD;
      pharmaceutical company, GlaxoSmithKline, is funding the study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 30, 2012</start_date>
  <completion_date type="Actual">July 31, 2012</completion_date>
  <primary_completion_date type="Actual">July 31, 2012</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse event reporting</measure>
    <time_frame>Day 1 through to within 7-10 days after the last dose</time_frame>
    <description>Change in health of subjects</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in clinical chemistry, hematology, urinalysis</measure>
    <time_frame>Cohort A: D-1, predose (each session), D2 (each session) and 7-10 days after the last dose. Cohort B single dose session: D-3, predose, D2. Cohort B repeat dose session: D1, D2, D5, D10, D11, D14 and within 7-10 days after last dose</time_frame>
    <description>Change in clinical chemistry, hematology and urinalysis from baseline</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in vital signs parameters</measure>
    <time_frame>Cohort A: Predose, 2h post dose, D2, within 7-10 days from last dose. Cohort B single dose session: D-3, predose, 2h post-dose, D2. Cohort B repeat dose session: predose on D1, D2, D5, D10, 2h post-dose on D1 and D10, D14, within 7-10 days post last dose</time_frame>
    <description>Change in blood pressure, heart rate and body temperature outside normal range</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline in ECG parameters</measure>
    <time_frame>Cohort A: Predose, 2h post dose, D2 and within 7-10 days of last dose. Cohort B single dose session: D-3, pre-dose, 2h post-dose and D2. Cohort B repeat dose session: pre-dose, D2, D5, D10, 2h post-dose on D1, D10, D14 and within 7-10 days from last dose</time_frame>
    <description>Change in ECG parameters outside normal range</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Plasma concentrations of GSK2586184</measure>
    <time_frame>Cohort A: 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B single dose session:0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B repeat dose session: D1 and D10 (predose, 0.25, 0.5, 1, 2, 4, 8 and 12h post-dose), D2, D3, D4, D5, and D11</time_frame>
    <description>Change in plasma concentrations of GSK2586184</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from baseline for 24h urine albumin, creatinine and PCR</measure>
    <time_frame>Cohort B repeat dose: D-1, D10 and within 7-10 days post last dose</time_frame>
    <description>Change in 24h urine creatinine, albumin and PCR values outside normal range</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>mRNA expression of IFNa and JAK pathway genes</measure>
    <time_frame>Cohort B repeat dose: Predose, 1, 2, 4, 8 and 12h on D1 and D10. Predose, 1, 2, 4, 8, 12 and 24h post-dose on D11</time_frame>
    <description>Change in mRNA expression profile of IFNa and JAK pathway genes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vital signs as a pharmacodynamic endpoint</measure>
    <time_frame>Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11</time_frame>
    <description>Change in blood pressure, heart rate and body temperature post IFNa challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma levels of Neopterin and B2-microglobulin</measure>
    <time_frame>Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11</time_frame>
    <description>Change in plasma concentrations of neopterin and B2-microglobulin post IFNa challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Glomerular Filtration Measurement using Cr-51 EDTA</measure>
    <time_frame>Cohort B: 2h and 4h post Cr-51 EDTA injection on D-2 of single dose session, D8 of repeat dose session and within 7-10 days post last dose</time_frame>
    <description>Change in plasma concentrations of Cr-51 EDTA and it's derived clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duodenal concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters</measure>
    <time_frame>Cohort A: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose. Cohort B single dose: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose</time_frame>
    <description>Change in bile concentrations of GSK2586184 and it's metabolites</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Urine concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters</measure>
    <time_frame>Cohort A: D1 predose and for 24 hr post-dose.Cohort B single dose: D1 predose and for 24h post-dose</time_frame>
    <description>Change in urine concentration of GSK2586184 and it's metabolites</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Systemic Lupus Erythematosus</condition>
  <arm_group>
    <arm_group_label>Cohort A fed session</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>GSK2586184 800mg single dose with food</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort A fasted session</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>GSK2586184 single dose without food</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B active study medication</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>GSK2586184 800mg single and twice daily dose for 13 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo-to-match single and twice daily dose for 13 days</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2586184 800mg single and repeat dose</intervention_name>
    <description>GSK2586184 800mg single dose and then twice daily dosing for 13 days</description>
    <arm_group_label>Cohort B active study medication</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo-to-match GSK2586184</intervention_name>
    <description>Placebo-to-match GSK2586184</description>
    <arm_group_label>Cohort B placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>GSK2586184 single dose taken with food</intervention_name>
    <description>GSK2586184 single dose taken with FDA approved high fat, high calorie breakfast</description>
    <arm_group_label>Cohort A fed session</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>GSK2586184 single dose taken without food</intervention_name>
    <description>GSK2586184 single dose taken in a fasted state</description>
    <arm_group_label>Cohort A fasted session</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy as determined by a responsible and experienced physician, based on a medical&#xD;
             evaluation including medical history, physical examination, laboratory tests and&#xD;
             cardiac monitoring&#xD;
&#xD;
          -  Cohort A: A female subject of non-childbearing potential defined as pre-menopausal&#xD;
             females with a documented tubal ligation or hysterectomy; or postmenopausal defined as&#xD;
             12 months of spontaneous amenorrhea&#xD;
&#xD;
          -  Cohort B: Male subjects with female partners of child-bearing potential must agree to&#xD;
             contraception method mandated by protocol&#xD;
&#xD;
          -  Cohort A: Subjects between 18 and 65 years of age inclusive, at the time of signing&#xD;
             the informed consent&#xD;
&#xD;
          -  Cohort B: Subjects between 18 and 50 years of age inclusive, at the time of signing&#xD;
             the informed consent&#xD;
&#xD;
          -  Normal creatinine clearance values at screening&#xD;
&#xD;
          -  ALT, alkaline phosphatase and bilirubin ≤ 1.5xULN (isolated bilirubin &gt;1.5xULN is&#xD;
             acceptable if bilirubin is fractionated and direct bilirubin &lt;35%)&#xD;
&#xD;
          -  Single QTcF &lt; 480 msec&#xD;
&#xD;
          -  BMI within the range 18 - 30.0 kg/m2 (inclusive)&#xD;
&#xD;
          -  Subjects must be non-smokers and must not use any nicotine-containing products. A&#xD;
             non-smoker is defined as an individual who has abstained from smoking for at least 1&#xD;
             year prior to screening&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result within 3 months of screening&#xD;
&#xD;
          -  Current or chronic history of liver disease, or known hepatic or biliary abnormalities&#xD;
             (with the exception of Gilbert's syndrome or asymptomatic gallstones)&#xD;
&#xD;
          -  A positive pre-study drug/alcohol screen&#xD;
&#xD;
          -  A positive test for HIV antibody&#xD;
&#xD;
          -  History of sensitivity to any of the study medications, Intron A or other recombinant&#xD;
             interferons, or components thereof or a history of drug or other allergy that, in the&#xD;
             opinion of the investigator or GSK Medical Monitor, contraindicates their&#xD;
             participation&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as an&#xD;
             average weekly intake of &gt;21 units for males or &gt;14 units for females. One unit is&#xD;
             equivalent to 8 g of alcohol and the following can be used as a guide: a half-pint&#xD;
             (~240 ml) of beer, 1 glass (125 ml) of wine or 1 (25 ml) measure of spirits&#xD;
&#xD;
          -  The subject has participated in a clinical trial and has received an investigational&#xD;
             product within the following time period prior to the first dosing day in the current&#xD;
             study: 30 days, 5 half-lives or twice the duration of the biological effect of the&#xD;
             investigational product (whichever is longer)&#xD;
&#xD;
          -  The subject is unwilling to abstain from alcohol consumption from 48 hr prior to&#xD;
             dosing until discharge from the clinic, and for 24 hr prior to all other out-patient&#xD;
             clinic visits&#xD;
&#xD;
          -  Exposure to more than four new chemical entities within 12 months prior to the first&#xD;
             dosing day&#xD;
&#xD;
          -  Unable to refrain from the use of prescription or non-prescription drugs, including&#xD;
             vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or&#xD;
             14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is&#xD;
             longer) prior to the first dose of study medication, unless in the opinion of the&#xD;
             Investigator and GSK Medical Monitor the medication will not interfere with the study&#xD;
             procedures or compromise subject safety&#xD;
&#xD;
          -  History of malignancy, except for adequately treated non-invasive cancer of the skin&#xD;
             (basal or squamous cell) or cervical carcinoma in situ (&gt;2 yrs prior to dosing)&#xD;
&#xD;
          -  Where participation in the study would result in donation of blood or blood products&#xD;
             in excess of 500 mL within a 56 day period&#xD;
&#xD;
          -  Subjects with a history of or a current thyroid disease or epilepsy&#xD;
&#xD;
          -  Subjects exposed to radiation in the 6 months, (except for X-ray/CT examinations of&#xD;
             the extremities) prior to the first GFR assessment (Day -2) (cohort B only)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Antwerpen</city>
        <zip>2060</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>May 10, 2012</study_first_submitted>
  <study_first_submitted_qc>September 13, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 18, 2012</study_first_posted>
  <last_update_submitted>May 24, 2018</last_update_submitted>
  <last_update_submitted_qc>May 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 25, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lupus Erythematosus, Systemic</mesh_term>
  </condition_browse>
  <!-- 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/NCT01687309
org study id: 116439
nct id: NCT01687309
lead sponsor: 
has dmc: No
A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of
      single and repeat doses of 800 mg GSK2586184 in healthy subjects.
This is a study in healthy volunteers to investigate the safety, tolerability,
      pharmacokinetics (the body's effect on the drug) and pharmacodynamics (the drug's effect on
      the body) of single and repeat doses of 800 mg GSK2586184. The effect of food and gender on
      pharmacokinetics will also be investigated following single dosing.

      The study is made up of 2 groups of healthy subjects. The first group consists of 6 female
      subjects who will receive a single dose of 800mg GSK2586184 (study medication) during 2
      seperate sessions. One session will involve the female subjects taking the study medication
      with food and the other session will involve study medication being taken without food. The
      safety and tolerability of the study medication in female subjects and the effect of food on
      the pharmacokinetics of the study medication will be investigated.

      The second group will consist of 12 healthy male subjects participating in 2 sessions. 8
      subjects will receive study medication and 4 will receive placebo (dummy medication) during
      the course of the study. Neither they or their study doctor will know which one they are
      given. Each male subject will receive a single dose of study medication or placebo followed
      by 13 days of twice daily dosing of study medication or placebo. Each dose will be taken with
      food.The single dose results from this group of subjects will be compared to the female group
      to investigate the effect of gender on pharmacokinetics. The safety and pharmacokinetics of
      repeat dosing will be investigated. The effect of repeat dosing on kidney function and the
      immune system will also be investigated.

      The study will take place in the SGS Clinical Pharmacology Unit in Antwerp, Belgium. A
      pharmaceutical company, GlaxoSmithKline, is funding the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Adverse event reporting
time frame: Day 1 through to within 7-10 days after the last dose
description: Change in health of subjects
measure: Change from baseline in clinical chemistry, hematology, urinalysis
time frame: Cohort A: D-1, predose (each session), D2 (each session) and 7-10 days after the last dose. Cohort B single dose session: D-3, predose, D2. Cohort B repeat dose session: D1, D2, D5, D10, D11, D14 and within 7-10 days after last dose
description: Change in clinical chemistry, hematology and urinalysis from baseline
measure: Change from baseline in vital signs parameters
time frame: Cohort A: Predose, 2h post dose, D2, within 7-10 days from last dose. Cohort B single dose session: D-3, predose, 2h post-dose, D2. Cohort B repeat dose session: predose on D1, D2, D5, D10, 2h post-dose on D1 and D10, D14, within 7-10 days post last dose
description: Change in blood pressure, heart rate and body temperature outside normal range
measure: Change from baseline in ECG parameters
time frame: Cohort A: Predose, 2h post dose, D2 and within 7-10 days of last dose. Cohort B single dose session: D-3, pre-dose, 2h post-dose and D2. Cohort B repeat dose session: pre-dose, D2, D5, D10, 2h post-dose on D1, D10, D14 and within 7-10 days from last dose
description: Change in ECG parameters outside normal range
measure: Plasma concentrations of GSK2586184
time frame: Cohort A: 0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B single dose session:0.25, 0.5, 1, 2, 4, 8, 12, 24 and 48h post-dose. Cohort B repeat dose session: D1 and D10 (predose, 0.25, 0.5, 1, 2, 4, 8 and 12h post-dose), D2, D3, D4, D5, and D11
description: Change in plasma concentrations of GSK2586184
measure: Change from baseline for 24h urine albumin, creatinine and PCR
time frame: Cohort B repeat dose: D-1, D10 and within 7-10 days post last dose
description: Change in 24h urine creatinine, albumin and PCR values outside normal range
measure: mRNA expression of IFNa and JAK pathway genes
time frame: Cohort B repeat dose: Predose, 1, 2, 4, 8 and 12h on D1 and D10. Predose, 1, 2, 4, 8, 12 and 24h post-dose on D11
description: Change in mRNA expression profile of IFNa and JAK pathway genes
measure: Vital signs as a pharmacodynamic endpoint
time frame: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11
description: Change in blood pressure, heart rate and body temperature post IFNa challenge
measure: Plasma levels of Neopterin and B2-microglobulin
time frame: Cohort B repeat dose: Predose, 4, 8, 12, 24, 28, 32, 48, 72, 100 and 120h post dose on D11
description: Change in plasma concentrations of neopterin and B2-microglobulin post IFNa challenge
measure: Glomerular Filtration Measurement using Cr-51 EDTA
time frame: Cohort B: 2h and 4h post Cr-51 EDTA injection on D-2 of single dose session, D8 of repeat dose session and within 7-10 days post last dose
description: Change in plasma concentrations of Cr-51 EDTA and it's derived clearance
measure: Duodenal concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters
time frame: Cohort A: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose. Cohort B single dose: D-1 to D1 predose and 2.5h post-dose to 6.5h post-dose
description: Change in bile concentrations of GSK2586184 and it's metabolites
measure: Urine concentrations of GSK2586184 and its metabolites and derived pharmacokinetic parameters
time frame: Cohort A: D1 predose and for 24 hr post-dose.Cohort B single dose: D1 predose and for 24h post-dose
description: Change in urine concentration of GSK2586184 and it's metabolites
arm group label: Cohort A fed session
arm group type: Other
description: GSK2586184 800mg single dose with food
arm group label: Cohort A fasted session
arm group type: Other
description: GSK2586184 single dose without food
arm group label: Cohort B active study medication
arm group type: Active Comparator
description: GSK2586184 800mg single and twice daily dose for 13 days
arm group label: Cohort B placebo
arm group type: Placebo Comparator
description: Placebo-to-match single and twice daily dose for 13 days
intervention type: Drug
intervention name: GSK2586184 800mg single and repeat dose
description: GSK2586184 800mg single dose and then twice daily dosing for 13 days
arm group label: Cohort B active study medication
intervention type: Drug
intervention name: Placebo-to-match GSK2586184
description: Placebo-to-match GSK2586184
arm group label: Cohort B placebo
intervention type: Other
intervention name: GSK2586184 single dose taken with food
description: GSK2586184 single dose taken with FDA approved high fat, high calorie breakfast
arm group label: Cohort A fed session
intervention type: Other
intervention name: GSK2586184 single dose taken without food
description: GSK2586184 single dose taken in a fasted state
arm group label: Cohort A fasted session
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: Belgium
responsible party type: Sponsor
mesh term: Lupus Erythematosus, Systemic