<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/NCT01674322</url>
  </required_header>
  <id_info>
    <org_study_id>CR100885</org_study_id>
    <secondary_id>PCI-32765CLL1004</secondary_id>
    <secondary_id>2012-002087-27</secondary_id>
    <nct_id>NCT01674322</nct_id>
  </id_info>
  <brief_title>A Study to Determine the Absorption, Metabolism, and Routes of Excretion of (14C) Radiolabeled Ibrutinib in Healthy Male Participants</brief_title>
  <official_title>An Open-Label Phase 1 Study to Determine the Pharmacokinetics, Metabolism, and Routes of Excretion of (14C) Radiolabeled PCI-32765 in Healthy Male Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Janssen Research &amp; Development, LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Janssen Research &amp; Development, LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to investigate the absorption, the metabolic pathways and the&#xD;
      excretion of ibrutinib in healthy male adult participants after administration of a single&#xD;
      oral dose of 50 mg to 140 mg (5 mg/mL solution) of unlabeled ibrutinib admixed with 14C&#xD;
      ibrutinib.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label (all people know the identity of the intervention), single-center,&#xD;
      single-dose study in healthy male participants. Six men will be enrolled to allow a minimum&#xD;
      of 4 participants to complete the study. All participants will receive a single oral solution&#xD;
      dose of 50 to 140 mg ibrutinib containing 1480 kBq (40 µCi) of 14C labeled ibrutinib,&#xD;
      constituting a total radiation burden of approximately 0.916 mSv (ICRP risk category IIa).&#xD;
      The duration of the study is approximately 73 days including screening period of 28 days,&#xD;
      treatment period of 15 days, and follow-up period of 30 days. Safety will include adverse&#xD;
      events, laboratory safety, 12 lead electrocardiogram, physical examination, and vital signs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">September 2012</completion_date>
  <primary_completion_date type="Actual">September 2012</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum concentration (Cmax) of ibrutinib</measure>
    <time_frame>Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)</time_frame>
    <description>Pharmacokinetic parameter Cmax of ibrutinib will be determined.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Time to reach the maximum concentration (tmax) of ibrutinib</measure>
    <time_frame>Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)</time_frame>
    <description>Pharmacokinetic parameter tmax of ibrutinib will be determined.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the concentration-time curve (AUC) of ibrutinib</measure>
    <time_frame>Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)</time_frame>
    <description>Pharmacokinetic parameter AUC of ibrutinib will be determined.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Amount excreted into the urine (Ae) of ibrutinib</measure>
    <time_frame>Day -1, Day 1 over intervals 0-2, 2-4, 4-8, 8-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours, Days 9-15</time_frame>
    <description>Pharmacokinetic parameter Ae of ibrutinib will be determined by multiplying the urinary volume with the urinary concentration.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 73 days</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Healthy Participants</condition>
  <arm_group>
    <arm_group_label>Ibrutinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ibrutinib</intervention_name>
    <description>Type=exact number, unit=mg, number=50-140, form=solution, route=oral. Participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.</description>
    <arm_group_label>Ibrutinib</arm_group_label>
    <other_name>PCI-32765</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant must sign an informed consent document indicating they understand the&#xD;
             purpose of and procedures required for the study, including DNA analysis, and are&#xD;
             willing to participate in the study&#xD;
&#xD;
          -  Must agree to use an adequate contraception method as deemed appropriate by the&#xD;
             investigator (eg, vasectomy, double-barrier, partner using effective contraception)&#xD;
             during the study and for 3 months after receiving the study drug&#xD;
&#xD;
          -  Must agree to not donate sperm during the study and for 3 months after receiving the&#xD;
             study drug&#xD;
&#xD;
          -  Blood pressure (after the participant is supine for 5 minutes) between 90 and 140 mmHg&#xD;
             systolic, inclusive, and no higher than 90 mmHg diastolic&#xD;
&#xD;
          -  Non-smoker (not smoked for 6 months prior to screening)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of or current clinically significant medical illness including cardiac&#xD;
             arrhythmias or other cardiac disease, hematologic disease, coagulation disorders,&#xD;
             lipid abnormalities, significant pulmonary disease, including bronchospastic&#xD;
             respiratory disease, diabetes mellitus, renal or hepatic insufficiency, thyroid&#xD;
             disease, neurologic or psychiatric disease&#xD;
&#xD;
          -  Clinically significant abnormal values for hematology, coagulation and platelet&#xD;
             function, clinical chemistry or urinalysis at screening as deemed appropriate by the&#xD;
             investigator&#xD;
&#xD;
          -  Clinically significant abnormal physical examination, vital signs or 12 lead&#xD;
             electrocardiogram (ECG) at screening as deemed appropriate by the investigator&#xD;
&#xD;
          -  History of clinically significant allergies, especially known hypersensitivity or&#xD;
             intolerance to β-lactam antibiotics or sulfonamides&#xD;
&#xD;
          -  Known allergy to heparin or history of heparin induced thrombocytopenia&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Janssen Research &amp; Development, LLC Clinical Trial</last_name>
    <role>Study Director</role>
    <affiliation>Janssen Research &amp; Development, LLC</affiliation>
  </overall_official>
  <location>
    <facility>
      <address>
        <city>Merksem</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
  </location_countries>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 24, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 28, 2012</study_first_posted>
  <last_update_submitted>November 4, 2014</last_update_submitted>
  <last_update_submitted_qc>November 4, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 5, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Healthy participants</keyword>
  <keyword>Ibrutinib</keyword>
  <keyword>PCI-32765</keyword>
  <keyword>B-cell malignancies</keyword>
  <keyword>CYP3A4</keyword>
  <!-- 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/NCT01674322
org study id: CR100885
secondary id: PCI-32765CLL1004
secondary id: 2012-002087-27
nct id: NCT01674322
lead sponsor: 
has dmc: No
The purpose of this study is to investigate the absorption, the metabolic pathways and the
      excretion of ibrutinib in healthy male adult participants after administration of a single
      oral dose of 50 mg to 140 mg (5 mg/mL solution) of unlabeled ibrutinib admixed with 14C
      ibrutinib.
This is an open-label (all people know the identity of the intervention), single-center,
      single-dose study in healthy male participants. Six men will be enrolled to allow a minimum
      of 4 participants to complete the study. All participants will receive a single oral solution
      dose of 50 to 140 mg ibrutinib containing 1480 kBq (40 µCi) of 14C labeled ibrutinib,
      constituting a total radiation burden of approximately 0.916 mSv (ICRP risk category IIa).
      The duration of the study is approximately 73 days including screening period of 28 days,
      treatment period of 15 days, and follow-up period of 30 days. Safety will include adverse
      events, laboratory safety, 12 lead electrocardiogram, physical examination, and vital signs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum concentration (Cmax) of ibrutinib
time frame: Day 1 (Predose, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
description: Pharmacokinetic parameter Cmax of ibrutinib will be determined.
measure: Time to reach the maximum concentration (tmax) of ibrutinib
time frame: Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
description: Pharmacokinetic parameter tmax of ibrutinib will be determined.
measure: Area under the concentration-time curve (AUC) of ibrutinib
time frame: Predose, Day 1 (0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 16 hours), Day 2 (24 hours), Day 3 (48 hours), Day 4 (72 hours)
description: Pharmacokinetic parameter AUC of ibrutinib will be determined.
measure: Amount excreted into the urine (Ae) of ibrutinib
time frame: Day -1, Day 1 over intervals 0-2, 2-4, 4-8, 8-24, 24-48, 48-72, 72-96, 96-120, 120-144, 144-168 hours, Days 9-15
description: Pharmacokinetic parameter Ae of ibrutinib will be determined by multiplying the urinary volume with the urinary concentration.
measure: Number of patients with adverse events
time frame: Up to 73 days
arm group label: Ibrutinib
arm group type: Experimental
description: All participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.
intervention type: Drug
intervention name: Ibrutinib
description: Type=exact number, unit=mg, number=50-140, form=solution, route=oral. Participants will receive a single oral solution dose of 50 mg to 140 mg -ibrutinib containing 1480 kBq (40 µCi) of 14C-labeled ibrutinib, with a total radiation burden of approximately 0.916 mSv.
arm group label: Ibrutinib
other name: PCI-32765
criteria: 
gender: Male
minimum age: 30 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Janssen Research & Development, LLC Clinical Trial
role: Study Director
affiliation: Janssen Research & Development, LLC
facility: 
country: Belgium
responsible party type: Sponsor