<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/NCT01696604</url>
  </required_header>
  <id_info>
    <org_study_id>116715</org_study_id>
    <nct_id>NCT01696604</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK2849466 in Healthy Male Subjects</brief_title>
  <official_title>A Single-center, Randomized, Blinded, Placebo-controlled Two-part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Selective Androgen Receptor Modulator (SARM), GSK2849466, in Single and Repeat Doses, With and Without Food, in Healthy Male 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>
      This study is the first administration of GSK2849466 in humans. This will be a single centre,&#xD;
      randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability,&#xD;
      pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat&#xD;
      oral doses up to 14 days to healthy male subjects. Part A will be a randomized placebo&#xD;
      controlled and 4-way crossover study. It will include two cohorts of 8 subjects each. In each&#xD;
      cohort there will be 4 study periods each approximately of 1 week including 6 days of&#xD;
      washout. Each subject will receive a total of 3 active doses as ascending single oral dose of&#xD;
      GSK2849466 and 1 placebo dose during the course of their participation in the study. The&#xD;
      first (&quot;bridging dose&quot;) dose provided to subjects in Cohort 2 will be the same as the last&#xD;
      dose provided to subjects in Cohort 1. The single doses of GSK2849466 planned in Part A of&#xD;
      this study are: 0.01, 0.03, 0.1, and 0.3 milligram (mg) in Cohort 1 and 0.3, 1, 3, and 10 mg&#xD;
      in Cohort 2. In cohorts 1 and 2 all available safety, tolerability, and PK data will be&#xD;
      reviewed prior to each dose escalation. The dosing schedule in Part A may be adjusted to&#xD;
      expand a cohort or to add an additional cohort(s) in order to further evaluate additional&#xD;
      doses or repeat evaluation of a dose level already studied. Part B will be a randomized&#xD;
      placebo controlled, parallel group study. It will include three cohorts of 12 subjects each.&#xD;
      Each subject will receive repeat doses of GSK2849466 over 14 days. The doses chosen for Part&#xD;
      B will be based on the safety, tolerability, and PK data from Part A. Subjects in Cohort 4&#xD;
      (and/or an another cohort [s] as determined based on Part A PK data) will be dosed in the&#xD;
      fasted state on Days 1 and 14 and in the fed state on Day 7 when subjects will receive a&#xD;
      standard meal 30 minutes prior to dosing. Part B will provide sufficient safety and&#xD;
      tolerability data to bridge to longer duration studies. The study duration, including&#xD;
      screening and follow-up, is not expected to exceed 70 days for subjects in the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 26, 2012</start_date>
  <completion_date type="Actual">May 3, 2013</completion_date>
  <primary_completion_date type="Actual">May 3, 2013</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>Crossover Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability parameters will include recording of AEs, throughout the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of repeat doses of GSK2849466 as assessed by number of subjects with AEs</measure>
    <time_frame>14 days</time_frame>
    <description>Safety and tolerability parameters will include recording of AEs, throughout the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in electrocardiogram (ECG) readings</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in ECG readings</measure>
    <time_frame>14 days</time_frame>
    <description>Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure</measure>
    <time_frame>14 days</time_frame>
    <description>Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in heart rate</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability parameters will include heart rate at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in heart rate</measure>
    <time_frame>14 days</time_frame>
    <description>Safety and tolerability parameters will include heart rate at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of GSK2849466 as assessed by change from Baseline in cardiac telemetry</measure>
    <time_frame>Part A-Day 1 continuous at least 12 hours post-dose of each dosing session; Part B-Day 1, 4, 7, 10 and 14 continuous at least 8 hours post-dose</time_frame>
    <description>Safety and tolerability parameters will include cardiac telemetry recording at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in laboratory assessments</measure>
    <time_frame>28 days</time_frame>
    <description>Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in laboratory assessments</measure>
    <time_frame>14 days</time_frame>
    <description>Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) following single doses of GSK2849466</measure>
    <time_frame>2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.</time_frame>
    <description>The AUC(0-t) and AUC(0-inf) for GSK2849466 will be assessed following single doses of GSK2849466.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration (Cmax) following single doses of GSK2849466</measure>
    <time_frame>2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.</time_frame>
    <description>The Cmax of GSK2849466 will be assessed following single doses of GSK2849466.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to maximum observed plasma drug concentration (Tmax) following single doses of GSK2849466</measure>
    <time_frame>2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.</time_frame>
    <description>The Tmax for GSK2849466 will be assessed following single doses of GSK2849466.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life (t1/2) following single doses of GSK2849466</measure>
    <time_frame>2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.</time_frame>
    <description>The t1/2 for GSK2849466 will be assessed following single doses of GSK2849466.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The AUC(0-t), AUC(0-inf)) and AUC from time zero to the end of the dosing interval at steady state AUC(0-tau) following repeat doses of GSK2849466</measure>
    <time_frame>Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.</time_frame>
    <description>The AUC(0-t), AUC(0-inf) and AUC(0-tau) following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Cmax following repeat doses of GSK2849466</measure>
    <time_frame>Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.</time_frame>
    <description>The Cmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Tmax following repeat doses of GSK2849466</measure>
    <time_frame>Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.</time_frame>
    <description>The Tmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The t1/2 following repeat doses of GSK2849466</measure>
    <time_frame>Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.</time_frame>
    <description>The t1/2 following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The estimation of an accumulation ratio following repeat doses of GSK2849466</measure>
    <time_frame>Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.</time_frame>
    <description>The estimation of an accumulation ratio following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Cachexia</condition>
  <arm_group>
    <arm_group_label>Part A: Cohort 1-GSK2849466</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive single planned dose of GSK284946 in ascending order (0.01, 0.03, 0.1, and 0.3 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Cohort 1-Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive single dose of matching placebo in one of the 4 treatment periods.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Cohort 2-GSK2849466</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive single planned dose of GSK284946 in ascending order (0.3, 1, 3, and 10 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period in one of the 4 treatment periods.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A: Cohort 2-Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive single dose of matching placebo in one of the 4 treatment periods.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 3-GSK2849466 (Repeat dose 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 3-Placebo (Repeat dose 1)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive repeat dose of matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 4-GSK2849466 (Repeat dose 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. In Cohort 4 subjects will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 4-Placebo (Repeat dose 2)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive repeat doses of matching placebo.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 5-GSK2849466 (Repeat dose 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B: Cohort 5-Placebo (Repeat dose 3)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects will receive repeat doses of matching placebo.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>GSK2849466</intervention_name>
    <description>GSK2849466 will be available as capsules of dose strengths 0.01, 0.1, 1.0, and 2.5 mg.</description>
    <arm_group_label>Part A: Cohort 1-GSK2849466</arm_group_label>
    <arm_group_label>Part A: Cohort 2-GSK2849466</arm_group_label>
    <arm_group_label>Part B: Cohort 3-GSK2849466 (Repeat dose 1)</arm_group_label>
    <arm_group_label>Part B: Cohort 4-GSK2849466 (Repeat dose 2)</arm_group_label>
    <arm_group_label>Part B: Cohort 5-GSK2849466 (Repeat dose 3)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Matching placebo capsules will be available.</description>
    <arm_group_label>Part A: Cohort 1-Placebo</arm_group_label>
    <arm_group_label>Part A: Cohort 2-Placebo</arm_group_label>
    <arm_group_label>Part B: Cohort 3-Placebo (Repeat dose 1)</arm_group_label>
    <arm_group_label>Part B: Cohort 4-Placebo (Repeat dose 2)</arm_group_label>
    <arm_group_label>Part B: Cohort 5-Placebo (Repeat dose 3)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males between 18 and 50 years of age (inclusive), at the time of signing the informed&#xD;
             consent form.&#xD;
&#xD;
          -  Body weight &gt;=50 kilogram (kg) and Body Mass Index (BMI) within the range 19 - 32&#xD;
             kg/meter (m)^2 (inclusive), where BMI = (weight in kg)/(height in meters)^2.&#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. A subject with a clinical abnormality or laboratory parameters&#xD;
             outside the reference range for the population being studied may be included only if&#xD;
             the Investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding&#xD;
             is unlikely to introduce additional risk factors and will not interfere with the study&#xD;
             procedures.&#xD;
&#xD;
          -  Male subjects with female partners of child-bearing potential must agree to use one of&#xD;
             the contraception methods listed in the Lifestyle Section of the protocol. This&#xD;
             criterion must be followed through the completion of the follow-up visit.&#xD;
&#xD;
          -  Capable of giving written informed consent, which includes compliance with the&#xD;
             requirements and restrictions listed in the consent form.&#xD;
&#xD;
          -  Average corrected QT interval using Fridericia's formulas (QTcF) &lt;450 milliseconds&#xD;
             (msec); or QTcF &lt;480 msec in subjects with Bundle Branch Block.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of clinically significant endocrine, gastrointestinal,&#xD;
             hepatic, cardiovascular, neurological, hematological, immunological, renal,&#xD;
             respiratory, or genitourinary abnormalities or diseases.&#xD;
&#xD;
          -  Subjects with a history at any time in the past of coronary artery disease, congestive&#xD;
             heart failure, angina, myocardial infarction, any cardiac surgery, valvular heart&#xD;
             disease, clinically significant arrhythmia, dyspnea, pulmonary edema, stroke, or&#xD;
             transient ischemic attack.&#xD;
&#xD;
          -  ECG exclusion criteria: Heart rate &lt;40 and &gt;100 beats per minute; PR Interval &lt;120 and&#xD;
             &gt;200 msec; QRS duration &lt;70 and &gt;110 msec.&#xD;
&#xD;
          -  Subjects with a history of malignancy that is not in complete remission for at least 5&#xD;
             years or 1 year for non-melanoma skin carcinoma.&#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;
          -  History of drug or alcohol abuse within 5 years prior to the Screening Period.&#xD;
&#xD;
          -  History of regular alcohol consumption within 6 months of the study defined as an&#xD;
             average weekly intake of &gt;14 drinks for males or &gt;7 drinks for females. One drink is&#xD;
             equivalent to 12 grams (g) of alcohol: 12 ounces (360 millilitre [mL]) of beer, 5&#xD;
             ounces (150 mL) of wine or 1.5 ounces (45 mL) of 80 proof distilled 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 GSK&#xD;
             Medical Monitor.&#xD;
&#xD;
          -  Subjects with a family history of early onset prostate cancer or multiple members with&#xD;
             prostate cancer.&#xD;
&#xD;
          -  A positive pre-study drug or alcohol screen.&#xD;
&#xD;
          -  Cotinine levels indicative of smoking or history or regular use of tobacco-or&#xD;
             nicotine-containing products within 6 months prior to screening.&#xD;
&#xD;
          -  Subjects with values outside the specified ranges for the following Key Clinical&#xD;
             Laboratory Tests must be excluded from the study: Liver function tests - Alanine&#xD;
             transaminase (ALT), Direct Bilirubin, or Albumin &gt;10% outside the normal reference&#xD;
             range (&lt;0.9 x lower limit of normal [LLN] or &gt;1.1 x Upper Limit of Normal [ULN]),&#xD;
             Renal function - Creatinine &lt;1.6 mg/ deciliter (dl) with an age appropriate Glomerular&#xD;
             filtration rate (GFR) &gt;=60 mL/min/1.73 m^2), Electrolytes - Sodium &gt; +,- 5&#xD;
             milliequivalents of solute per litre of solvent (mEq/L) outside the normal reference&#xD;
             range, Potassium or Calcium &gt;10% outside the normal reference range (&lt;0.9 x LLN or&#xD;
             &gt;1.1 x ULN), Metabolic - Glucose &gt;10% outside the normal reference range (&lt;0.9 x LLN&#xD;
             or &gt;1.1 x ULN) and Total Cholesterol &gt;240 mg/dl, Muscle - creatine phosphokinase &gt;2.0&#xD;
             x ULN, Hematology - Hemoglobin, WBC, Neutrophils, or Platelets &gt;10% outside the normal&#xD;
             reference range (&lt;0.9 x LLN or &gt;1.1 x ULN), Prostate Specific Antigen (PSA) &gt;=2.5&#xD;
             nanogram (ng)/mL.&#xD;
&#xD;
          -  A positive test for human immunodeficiency virus (HIV) antibody.&#xD;
&#xD;
          -  A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody&#xD;
             result within 3 months of screening.&#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 prescription or non-prescription drugs, including vitamins,&#xD;
             herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if&#xD;
             the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to&#xD;
             the first dose of study medication and throughout the study, unless in the opinion of&#xD;
             the Investigator and GSK Medical Monitor the medication will not interfere with the&#xD;
             study procedures or compromise subject safety.&#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: 3 months (12 weeks), 5 half-lives or twice the duration of the biological&#xD;
             effect of the investigational product (whichever is longer).&#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;
          -  Unable to refrain from consumption of red wine, seville oranges, grapefruit or&#xD;
             grapefruit juice from 7 days prior to the first dose of study medication.&#xD;
&#xD;
          -  Unwillingness or inability to follow the procedures outlined in the protocol&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <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>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.clinicalstudydatarequest.com</url>
    <description>Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.</description>
  </link>
  <verification_date>June 2017</verification_date>
  <study_first_submitted>September 27, 2012</study_first_submitted>
  <study_first_submitted_qc>September 27, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 1, 2012</study_first_posted>
  <last_update_submitted>June 6, 2017</last_update_submitted>
  <last_update_submitted_qc>June 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>safety</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>FTIH</keyword>
  <keyword>SARM</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cachexia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.</ipd_description>
  </patient_data>
  <study_docs>
    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Annotated Case Report Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Clinical Study Report</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Statistical Analysis Plan</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
    </study_doc>
    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Informed Consent Form</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Dataset Specification</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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    <study_doc>
      <doc_id>116715</doc_id>
      <doc_type>Study Protocol</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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    <study_doc>
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      <doc_type>Individual Participant Data Set</doc_type>
      <doc_url>https://www.clinicalstudydatarequest.com</doc_url>
      <doc_comment>For additional information about this study please refer to the GSK Clinical Study Register</doc_comment>
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  <!-- 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/NCT01696604
org study id: 116715
nct id: NCT01696604
lead sponsor: 
has dmc: No
This study is the first administration of GSK2849466 in humans. This will be a single centre,
      randomized, double-blind, placebo-controlled study, to investigate the safety, tolerability,
      pharmacokinetics (PK), and pharmacodynamics (PD) of GSK2849466, given as single and repeat
      oral doses up to 14 days to healthy male subjects. Part A will be a randomized placebo
      controlled and 4-way crossover study. It will include two cohorts of 8 subjects each. In each
      cohort there will be 4 study periods each approximately of 1 week including 6 days of
      washout. Each subject will receive a total of 3 active doses as ascending single oral dose of
      GSK2849466 and 1 placebo dose during the course of their participation in the study. The
      first ("bridging dose") dose provided to subjects in Cohort 2 will be the same as the last
      dose provided to subjects in Cohort 1. The single doses of GSK2849466 planned in Part A of
      this study are: 0.01, 0.03, 0.1, and 0.3 milligram (mg) in Cohort 1 and 0.3, 1, 3, and 10 mg
      in Cohort 2. In cohorts 1 and 2 all available safety, tolerability, and PK data will be
      reviewed prior to each dose escalation. The dosing schedule in Part A may be adjusted to
      expand a cohort or to add an additional cohort(s) in order to further evaluate additional
      doses or repeat evaluation of a dose level already studied. Part B will be a randomized
      placebo controlled, parallel group study. It will include three cohorts of 12 subjects each.
      Each subject will receive repeat doses of GSK2849466 over 14 days. The doses chosen for Part
      B will be based on the safety, tolerability, and PK data from Part A. Subjects in Cohort 4
      (and/or an another cohort [s] as determined based on Part A PK data) will be dosed in the
      fasted state on Days 1 and 14 and in the fed state on Day 7 when subjects will receive a
      standard meal 30 minutes prior to dosing. Part B will provide sufficient safety and
      tolerability data to bridge to longer duration studies. The study duration, including
      screening and follow-up, is not expected to exceed 70 days for subjects in the study.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Other
masking: Double (Participant, Investigator)
measure: Safety and tolerability of single ascending doses GSK2849466 as assessed by number of subjects with adverse events (AE)s
time frame: 28 days
description: Safety and tolerability parameters will include recording of AEs, throughout the study.
measure: Safety and tolerability of repeat doses of GSK2849466 as assessed by number of subjects with AEs
time frame: 14 days
description: Safety and tolerability parameters will include recording of AEs, throughout the study.
measure: Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in electrocardiogram (ECG) readings
time frame: 28 days
description: Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
measure: Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in ECG readings
time frame: 14 days
description: Safety and tolerability parameter will include the ECG readings at Baseline and at end of the study.
measure: Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
time frame: 28 days
description: Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
measure: Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in clinical monitoring of blood pressure
time frame: 14 days
description: Safety and tolerability parameters will include blood pressure readings at Baseline and at end of the study.
measure: Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in heart rate
time frame: 28 days
description: Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
measure: Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in heart rate
time frame: 14 days
description: Safety and tolerability parameters will include heart rate at Baseline and at end of the study.
measure: Safety and tolerability of GSK2849466 as assessed by change from Baseline in cardiac telemetry
time frame: Part A-Day 1 continuous at least 12 hours post-dose of each dosing session; Part B-Day 1, 4, 7, 10 and 14 continuous at least 8 hours post-dose
description: Safety and tolerability parameters will include cardiac telemetry recording at Baseline and at end of the study.
measure: Safety and tolerability of single ascending doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
time frame: 28 days
description: Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
measure: Safety and tolerability of repeat doses of GSK2849466 as assessed by change from Baseline in laboratory assessments
time frame: 14 days
description: Safety and tolerability parameters will include laboratory values at Baseline and at end of the study.
measure: Area under the time-concentration curve from time zero (pre-dose) to last time of quantifiable concentration (AUC(0-t)) and AUC from zero to infinity (AUC(0-inf)) following single doses of GSK2849466
time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
description: The AUC(0-t) and AUC(0-inf) for GSK2849466 will be assessed following single doses of GSK2849466.
measure: Maximum concentration (Cmax) following single doses of GSK2849466
time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
description: The Cmax of GSK2849466 will be assessed following single doses of GSK2849466.
measure: Time to maximum observed plasma drug concentration (Tmax) following single doses of GSK2849466
time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
description: The Tmax for GSK2849466 will be assessed following single doses of GSK2849466.
measure: Terminal half-life (t1/2) following single doses of GSK2849466
time frame: 2 days of each treatment period in Part A: Day 1-0.25, 0.5, 0.75, 1, 2, 3, 4, 6, 8, 12 hours post dose; Day 2-24 hours post Day 1 dose.
description: The t1/2 for GSK2849466 will be assessed following single doses of GSK2849466.
measure: The AUC(0-t), AUC(0-inf)) and AUC from time zero to the end of the dosing interval at steady state AUC(0-tau) following repeat doses of GSK2849466
time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
description: The AUC(0-t), AUC(0-inf) and AUC(0-tau) following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
measure: The Cmax following repeat doses of GSK2849466
time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
description: The Cmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
measure: The Tmax following repeat doses of GSK2849466
time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
description: The Tmax following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
measure: The t1/2 following repeat doses of GSK2849466
time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
description: The t1/2 following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
measure: The estimation of an accumulation ratio following repeat doses of GSK2849466
time frame: Part B (all cohorts): Day 1, 2, 14, 15(24 hours serial sampling); Day 4, 5, 6, 7 (pre dose sampling). Part B (Cohort 4): Day 7 and 8 (24 hours serial sampling) and no PK samples on Day 8 if fasted on Day 7.
description: The estimation of an accumulation ratio following repeat doses of GSK2849466 with and without food (Cohort 4 and/or another cohort(s) as determined based on Part A PK data) will be assessed in Part B of the study.
arm group label: Part A: Cohort 1-GSK2849466
arm group type: Experimental
description: The subjects will receive single planned dose of GSK284946 in ascending order (0.01, 0.03, 0.1, and 0.3 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period.
arm group label: Part A: Cohort 1-Placebo
arm group type: Experimental
description: The subjects will receive single dose of matching placebo in one of the 4 treatment periods.
arm group label: Part A: Cohort 2-GSK2849466
arm group type: Experimental
description: The subjects will receive single planned dose of GSK284946 in ascending order (0.3, 1, 3, and 10 mg) in ratio of 3:1.with placebo within each of 4 treatment periods. The dose will not be allowed to exceed 30 mg over a 24-hour period in one of the 4 treatment periods.
arm group label: Part A: Cohort 2-Placebo
arm group type: Experimental
description: The subjects will receive single dose of matching placebo in one of the 4 treatment periods.
arm group label: Part B: Cohort 3-GSK2849466 (Repeat dose 1)
arm group type: Experimental
description: The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo.
arm group label: Part B: Cohort 3-Placebo (Repeat dose 1)
arm group type: Experimental
description: The subjects will receive repeat dose of matching placebo.
arm group label: Part B: Cohort 4-GSK2849466 (Repeat dose 2)
arm group type: Experimental
description: The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo. In Cohort 4 subjects will be dosed in the fasted state on Days 1 and 14 and in the fed state on Day 7.
arm group label: Part B: Cohort 4-Placebo (Repeat dose 2)
arm group type: Experimental
description: The subjects will receive repeat doses of matching placebo.
arm group label: Part B: Cohort 5-GSK2849466 (Repeat dose 3)
arm group type: Experimental
description: The selection of appropriate doses for Part B will be performed upon consideration of available safety and tolerability and PK data from Part A and/or any preceding repeat dose cohorts. The subjects will receive GSK2849466 in ratio of 3:1.with placebo
arm group label: Part B: Cohort 5-Placebo (Repeat dose 3)
arm group type: Experimental
description: The subjects will receive repeat doses of matching placebo.
intervention type: Drug
intervention name: GSK2849466
description: GSK2849466 will be available as capsules of dose strengths 0.01, 0.1, 1.0, and 2.5 mg.
arm group label: Part A: Cohort 1-GSK2849466
arm group label: Part A: Cohort 2-GSK2849466
arm group label: Part B: Cohort 3-GSK2849466 (Repeat dose 1)
arm group label: Part B: Cohort 4-GSK2849466 (Repeat dose 2)
arm group label: Part B: Cohort 5-GSK2849466 (Repeat dose 3)
intervention type: Drug
intervention name: Placebo
description: Matching placebo capsules will be available.
arm group label: Part A: Cohort 1-Placebo
arm group label: Part A: Cohort 2-Placebo
arm group label: Part B: Cohort 3-Placebo (Repeat dose 1)
arm group label: Part B: Cohort 4-Placebo (Repeat dose 2)
arm group label: Part B: Cohort 5-Placebo (Repeat dose 3)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
country: United States
url: https://www.clinicalstudydatarequest.com
description: Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.
responsible party type: Sponsor
mesh term: Cachexia
sharing ipd: Yes
ipd description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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