<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/NCT03250039</url>
  </required_header>
  <id_info>
    <org_study_id>B7451008</org_study_id>
    <secondary_id>2017-000461-73</secondary_id>
    <nct_id>NCT03250039</nct_id>
  </id_info>
  <brief_title>Absorption, Metabolism, Excretion and Absolute Bioavailability</brief_title>
  <official_title>A Phase 1, Open-label, Non-randomized, 2-period, Fixed Sequence Study To Investigate The Absorption, Metabolism And Excretion Of [14c-pf-04965842] And To Assess The Absolute Bioavailability And Fraction Absorbed Of Pf-04965842 In Healthy Male Subjects Using A 14c-microtracer Approach</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Pfizer</source>
  <oversight_info>
    <has_dmc>No</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 study will investigate the absorption, metabolism and excretion of 14C-PF 04965842 and&#xD;
      characterize plasma, fecal and urinary radioactivity and identify any metabolites, if&#xD;
      possible, of 14C PF-04965842 in humans. In addition, this study will provide a better&#xD;
      understanding of the pharmacokinetic disposition of PF-04965842 by obtaining intravenous (IV)&#xD;
      clearance and delineating the extent of oral absorption (absolute bioavailability (F) and&#xD;
      fraction absorbed (Fa)).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 10, 2017</start_date>
  <completion_date type="Actual">September 15, 2017</completion_date>
  <primary_completion_date type="Actual">September 15, 2017</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>This study will be an open label, non randomized, 2 period, fixed sequence, single dose study to characterize the absorption, metabolism and excretion of 14C- PF-04965842 and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-04965842 following oral administration of unlabeled PF-04965842 and IV and oral administration of 14C-PF-04965842 to healthy male subjects.</intervention_model_description>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cumulative recovery of radioactivity</measure>
    <time_frame>From predose to Day 14 day</time_frame>
    <description>Total radioactivity in urine and feces based on total administered dose.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Maximum plasma concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Time to maximum concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUClast</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Area under the plasma concentration-time curve from time 0 to last quantifiable concentration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUCinf</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Area under the plasma concentration-time curve from time zero to infinity</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Apparent terminal elimination half-life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Apparent total body clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Apparent volume of distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vss (IV)</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Steady State Volume of distribution</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL (IV)</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Total Body Clearance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>F</measure>
    <time_frame>From predose to Day 5</time_frame>
    <description>Absolute bioavailability= ratio of the adjusted geometric means of dose normalized AUCinf for unlabeled PF-04965842 and IV labeled 14C-PF-04965842</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fa</measure>
    <time_frame>Predose to Day Day 5</time_frame>
    <description>Fraction of PF 04965842 dose absorbed = Total 14C urine data following both IV and oral administration of 14C PF 04965842 (quantification by AMS).</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>Mass Balance</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cumulative recovery of radioactivity in urine and feces</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Absolute Bioavailability</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral absolute bioavailability</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>PF-04965842</intervention_name>
    <description>14C labeled PF-04965842</description>
    <arm_group_label>Mass Balance</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Absolute Bioavailability</intervention_name>
    <description>Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842</description>
    <arm_group_label>Absolute Bioavailability</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male subjects who, at the time of screening, are between the ages of 18 and 55&#xD;
             years, inclusive. Healthy is defined as no clinically relevant abnormalities&#xD;
             identified by a detailed medical history, full physical examination, including blood&#xD;
             pressure and pulse rate measurement, 12 lead electrocardiogram (ECG), or clinical&#xD;
             laboratory tests.&#xD;
&#xD;
          2. Body Mass Index (BMI) of 17.5 to 30.5 kg/m2; and a total body weight &gt;50 kg (110 lbs).&#xD;
&#xD;
          3. Evidence of a personally signed and dated informed consent document indicating that&#xD;
             the subject has been informed of all pertinent aspects of the study.&#xD;
&#xD;
          4. Subjects who are willing and able to comply with study confinement period, scheduled&#xD;
             visits, treatment plan, laboratory tests, contraceptive requirements and other study&#xD;
             procedures.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
        Subjects with any of the following characteristics/conditions will not be included in the&#xD;
        study:&#xD;
&#xD;
          1. Evidence or history of clinically significant hematological, renal, endocrine,&#xD;
             pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, or&#xD;
             allergic disease (including drug allergies, but excluding untreated, asymptomatic,&#xD;
             seasonal allergies).&#xD;
&#xD;
          2. Any clinically significant malabsorption condition (eg, gastrectomy, bowel resection).&#xD;
&#xD;
          3. A positive urine drug screen for drugs of abuse or recreational drugs.&#xD;
&#xD;
          4. History of human immunodeficiency virus (HIV), hepatitis B, or hepatitis C; positive&#xD;
             testing for HIV, hepatitis B surface antigen (HepBsAg), hepatitis B core antibody&#xD;
             (HepBcAb), or hepatitis C antibody (HCVAb).&#xD;
&#xD;
          5. History of abuse of alcohol or binge drinking and/or any other illicit drug use or&#xD;
             dependence within 6 months of Screening. Binge drinking is defined as a pattern of 5&#xD;
             or more alcoholic drinks (male) in about 2 hours. As a general rule, alcohol intake&#xD;
             should not exceed 21 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a&#xD;
             125 mL glass of wine).&#xD;
&#xD;
          6. Use of tobacco/nicotine containing products in excess of 5 cigarettes/day.&#xD;
&#xD;
          7. Treatment with an investigational drug within 60 days.&#xD;
&#xD;
          8. Total 14C radioactivity measured in plasma exceeding 11 mBq/mL.&#xD;
&#xD;
          9. Screening supine blood pressure &gt;=140 mm Hg (systolic) or &gt;=90 mm Hg (diastolic),&#xD;
             following at least 5 minutes of supine rest. If blood pressure is &gt;=140 mm Hg&#xD;
             (systolic) or &gt;=90 mm Hg (diastolic), the blood pressure measurement should be&#xD;
             repeated two more times and the average of the three measurements should be used to&#xD;
             assess the subject's eligibility.&#xD;
&#xD;
         10. Supine 12 lead ECG demonstrating QTcF &gt;450 msec or a QRS interval &gt;120 msec at&#xD;
             screening. If QTcF exceeds 450 msec, or QRS exceeds 120 msec, the ECG should be&#xD;
             repeated two more times and the average of the three QTcF or QRS values should be used&#xD;
             to determine the subject's eligibility.&#xD;
&#xD;
         11. Use of prescription or nonprescription drugs (including vitamins and dietary&#xD;
             supplements) within 7 days or 5 half lives (whichever is longer) prior to the first&#xD;
             dose of study medication. As an exception, acetaminophen may be used at doses of =&lt;1&#xD;
             g/day. Limited use of non prescription medications that are not believed to affect&#xD;
             subject safety or the overall results of the study may be permitted on a case by case&#xD;
             basis following approval by Pfizer.&#xD;
&#xD;
         12. Use of herbal supplements within 28 days prior to the first dose of study medication.&#xD;
&#xD;
         13. Blood donation (excluding plasma donations) of no more than 100 mL or more within 56&#xD;
             days prior to dosing.&#xD;
&#xD;
         14. An estimated glomerular filtration rate of &lt;90 mL/min/1.73 m2 based on the four&#xD;
             variable Modification of Diet in Renal Disease (MDRD) equation.&#xD;
&#xD;
         15. History of tuberculosis or active or latent or inadequately treated infection,&#xD;
             positive QuantiFERON TB Gold test.&#xD;
&#xD;
         16. Any medical history of disease (ie, Gilbert's disease) that has the potential to cause&#xD;
             a rise in total bilirubin over the upper limit of normal (ULN).&#xD;
&#xD;
         17. Subjects with ANY of the following abnormalities in clinical laboratory tests at&#xD;
             Screening, as assessed by the study specific laboratory and confirmed by a single&#xD;
             repeat, if deemed necessary:&#xD;
&#xD;
               -  Serum aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt;=1.5 ×&#xD;
                  ULN, total serum bilirubin &gt;= 25.6 micromol/L;&#xD;
&#xD;
               -  Hemoglobin =&lt;2.17 mmol/L (males).&#xD;
&#xD;
         18. Known participation in a clinical trial for PF 04965842 within 60 days prior to the&#xD;
             first dose of study medication.&#xD;
&#xD;
         19. Serious adverse reaction or serious hypersensitivity to any drug or the formulation&#xD;
             excipients.&#xD;
&#xD;
         20. Unwilling or unable to comply with the Lifestyle Requirements described in this&#xD;
             protocol.&#xD;
&#xD;
         21. Subjects who are investigational site staff members directly involved in the conduct&#xD;
             of the study and their family members, site staff members otherwise supervised by the&#xD;
             Investigator, or subjects who are Pfizer employees, including their family members,&#xD;
             directly involved in the conduct of the study.&#xD;
&#xD;
         22. Systemic therapy with any of the following medications that are CYP3A4 inhibitors&#xD;
             within 7 days or 5 half lives (whichever is longer) or CYP3A inducers within 28 days&#xD;
             prior to the first dose of the trial medication, or during the trial (Section 5.7).&#xD;
&#xD;
         23. History of sensitivity to heparin or heparin induced thrombocytopenia.&#xD;
&#xD;
         24. Other acute or chronic medical or psychiatric condition including recent (within the&#xD;
             past year) or active suicidal ideation or behavior or laboratory abnormality that may&#xD;
             increase the risk associated with study participation or investigational product&#xD;
             administration or may interfere with the interpretation of study results and, in the&#xD;
             judgment of the investigator, would make the subject inappropriate for entry into this&#xD;
             study.&#xD;
&#xD;
         25. Subjects with conditions that affect their ability to taste ie, dysgeusia, respiratory&#xD;
             infection, cold, etc.&#xD;
&#xD;
         26. Male subjects who are unwilling or unable to use a highly effective method of&#xD;
             contraception as outlined in this protocol for the duration of the study and for at&#xD;
             least 90 days after the last dose of investigational product.&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <gender_based>Yes</gender_based>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Pfizer CT.gov Call Center</last_name>
    <role>Study Director</role>
    <affiliation>Pfizer</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>PRA Health Sciences</name>
      <address>
        <city>Groningen</city>
        <zip>9713 GZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PRA Health Sciences</name>
      <address>
        <city>Groningen</city>
        <zip>9728 NZ</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7451008&amp;StudyName=A+Phase+1%2C+Open-label%2C+Non-randomized%2C+2-period%2C+Fixed+Sequence%2C+Study+To+Investigate+The+Absorption%2C+Metabolism+And+Excretion+Of+%5B14c-pf-04965842%5D+And+To+Assess+The+Absolute+Bioavailability+And+Fraction+Absorbed+Of+Pf-04965842+In+Healthy+Male+Subjects+Using+A+14c+Microdose+Approach</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <link>
    <url>https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7451008&amp;StudyName=A+Phase+1%2C+Open-label%2C+Non-randomized%2C+2-period%2C+Fixed+Sequence+Study+To+Investigate+The+Absorption%2C+Metabolism+And+Excretion+Of+%5B14c-pf-04965842%5D+And+To+Assess+The+Absolute+Bioavailability+And+Fraction+Absorbed+Of+Pf-04965842+In+Healthy+Male+Subjects+Using+A+14c-microtracer+Approach</url>
    <description>To obtain contact information for a study center near you, click here.</description>
  </link>
  <verification_date>December 2017</verification_date>
  <study_first_submitted>July 11, 2017</study_first_submitted>
  <study_first_submitted_qc>August 10, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 15, 2017</study_first_posted>
  <last_update_submitted>December 19, 2017</last_update_submitted>
  <last_update_submitted_qc>December 19, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Absorption, Metabolism, Excretion, Absolute Bioavailability</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Abrocitinib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests</ipd_description>
  </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/NCT03250039
org study id: B7451008
secondary id: 2017-000461-73
nct id: NCT03250039
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This study will investigate the absorption, metabolism and excretion of 14C-PF 04965842 and
      characterize plasma, fecal and urinary radioactivity and identify any metabolites, if
      possible, of 14C PF-04965842 in humans. In addition, this study will provide a better
      understanding of the pharmacokinetic disposition of PF-04965842 by obtaining intravenous (IV)
      clearance and delineating the extent of oral absorption (absolute bioavailability (F) and
      fraction absorbed (Fa)).
allocation: Non-Randomized
intervention model: Crossover Assignment
intervention model description: This study will be an open label, non randomized, 2 period, fixed sequence, single dose study to characterize the absorption, metabolism and excretion of 14C- PF-04965842 and to evaluate the absolute oral bioavailability (F) and fraction absorbed (Fa) of PF-04965842 following oral administration of unlabeled PF-04965842 and IV and oral administration of 14C-PF-04965842 to healthy male subjects.
primary purpose: Other
masking: None (Open Label)
measure: Cumulative recovery of radioactivity
time frame: From predose to Day 14 day
description: Total radioactivity in urine and feces based on total administered dose.
measure: Cmax
time frame: From predose to Day 5
description: Maximum plasma concentration
measure: Tmax
time frame: From predose to Day 5
description: Time to maximum concentration
measure: AUClast
time frame: From predose to Day 5
description: Area under the plasma concentration-time curve from time 0 to last quantifiable concentration
measure: AUCinf
time frame: From predose to Day 5
description: Area under the plasma concentration-time curve from time zero to infinity
measure: t1/2
time frame: From predose to Day 5
description: Apparent terminal elimination half-life
measure: CL/F
time frame: From predose to Day 5
description: Apparent total body clearance
measure: Vz/F
time frame: From predose to Day 5
description: Apparent volume of distribution
measure: Vss (IV)
time frame: From predose to Day 5
description: Steady State Volume of distribution
measure: CL (IV)
time frame: From predose to Day 5
description: Total Body Clearance
measure: F
time frame: From predose to Day 5
description: Absolute bioavailability= ratio of the adjusted geometric means of dose normalized AUCinf for unlabeled PF-04965842 and IV labeled 14C-PF-04965842
measure: Fa
time frame: Predose to Day Day 5
description: Fraction of PF 04965842 dose absorbed = Total 14C urine data following both IV and oral administration of 14C PF 04965842 (quantification by AMS).
arm group label: Mass Balance
arm group type: Experimental
description: Cumulative recovery of radioactivity in urine and feces
arm group label: Absolute Bioavailability
arm group type: Experimental
description: Oral absolute bioavailability
intervention type: Drug
intervention name: PF-04965842
description: 14C labeled PF-04965842
arm group label: Mass Balance
intervention type: Drug
intervention name: Absolute Bioavailability
description: Oral dose of unlabeled PF-04965842 and an IV dose of 14C labeled PF- 04965842
arm group label: Absolute Bioavailability
criteria: 
gender: Male
gender based: Yes
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Pfizer CT.gov Call Center
role: Study Director
affiliation: Pfizer
facility: 
facility: 
country: Netherlands
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7451008&StudyName=A+Phase+1%2C+Open-label%2C+Non-randomized%2C+2-period%2C+Fixed+Sequence%2C+Study+To+Investigate+The+Absorption%2C+Metabolism+And+Excretion+Of+%5B14c-pf-04965842%5D+And+To+Assess+The+Absolute+Bioavailability+And+Fraction+Absorbed+Of+Pf-04965842+In+Healthy+Male+Subjects+Using+A+14c+Microdose+Approach
description: To obtain contact information for a study center near you, click here.
url: https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B7451008&StudyName=A+Phase+1%2C+Open-label%2C+Non-randomized%2C+2-period%2C+Fixed+Sequence+Study+To+Investigate+The+Absorption%2C+Metabolism+And+Excretion+Of+%5B14c-pf-04965842%5D+And+To+Assess+The+Absolute+Bioavailability+And+Fraction+Absorbed+Of+Pf-04965842+In+Healthy+Male+Subjects+Using+A+14c-microtracer+Approach
description: To obtain contact information for a study center near you, click here.
responsible party type: Sponsor
mesh term: Abrocitinib
sharing ipd: No
ipd description: Information relating to our policy on data sharing and the process for requesting data can be found at the following link: http://www.pfizer.com/research/clinical_trials/trial_data_and_results/data_requests