<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/NCT02238782</url>
  </required_header>
  <id_info>
    <org_study_id>D1532C00080</org_study_id>
    <nct_id>NCT02238782</nct_id>
  </id_info>
  <brief_title>A Study to Assess the Absolute Bioavailability of Oral Selumetinib in Healthy Male Volunteers.</brief_title>
  <official_title>A Study to Assess the Absolute Bioavailability of a Single Oral Dose of Selumetinib With Respect to an Intravenous Microdose of [14C] Selumetinib in Healthy Male Volunteers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AstraZeneca</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AstraZeneca</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the absolute bioavailability of oral selumetinib in healthy male volunteers&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">November 2014</completion_date>
  <primary_completion_date type="Actual">November 2014</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Absolute Bioavailability</measure>
    <time_frame>0 to 72 hours post-dose</time_frame>
    <description>To calculate absolute bioavailability we used the formula: Area Under the Curve (oral dose)/Area Under the Curve (intravenous dose)*100</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">21</enrollment>
  <condition>Healthy Volunteers Bioavailability Study</condition>
  <arm_group>
    <arm_group_label>selumetinib 75mg single dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>3 capsules of 25 mg administered orally</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>selumetinib 75mg single dose</intervention_name>
    <description>3 capsules of 25 mg given as a single dose</description>
    <arm_group_label>selumetinib 75mg single dose</arm_group_label>
    <other_name>Selumetinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>[14C] selumetinib IV solution</intervention_name>
    <description>single, radiolabeled, IV (infused), microdose (80 μg) of [14C] selumetinib, infused using a syringe pump as a 15-minute infusion, administered 1h 15 min after receiving the oral dose</description>
    <arm_group_label>selumetinib 75mg single dose</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Provision of written informed consent&#xD;
&#xD;
          2. Healthy male volunteers aged 18 to 65&#xD;
&#xD;
          3. Male volunteers with sexual partners who are pregnant or who could become pregnant&#xD;
             should use two highly effective methods of contraception (including one barrier&#xD;
             method) for at least 14 days after completing the study and should avoid sperm&#xD;
             donation for 14 days after study completion.&#xD;
&#xD;
          4. Body mass index between 18 and 30 kg/m2 and weighing between 50 and 100 kg.&#xD;
&#xD;
          5. Use no nicotine containing products for at least 3 months prior to screening with a&#xD;
             negative cotinine screen at screening and Day 1 (Visit 2)&#xD;
&#xD;
          6. Calculated creatinine clearance greater than 50 mL/min using Cockcroft Gault formula.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Involvement in the planning and/or conduct of the study&#xD;
&#xD;
          2. Previous enrolment for treatment in the present study&#xD;
&#xD;
          3. Japanese or non Japanese Asian or Indian ethnicity.&#xD;
&#xD;
          4. Any one parent or grandparent is Japanese or non-Japanese Asian or Indian.&#xD;
&#xD;
          5. Treatment with another new chemical entity or participation in any other clinical&#xD;
             study that included drug treatment within at least 3 months&#xD;
&#xD;
          6. Participation in another clinical study involving administration of [14C]&#xD;
             radioactivity within 1 year.&#xD;
&#xD;
          7. Current or past history of central serious retinopathy or retinal vein thrombosis,&#xD;
             intraocular pressure greater than 21 mmHg or uncontrolled glaucoma.&#xD;
&#xD;
          8. Any clinically significant disease or disorder which, may put the volunteer at risk&#xD;
             because of participation in the study, influence the study result or influence the&#xD;
             volunteer's ability to participate in the study.&#xD;
&#xD;
          9. Any clinically relevant abnormal findings in physical examination, haematology,&#xD;
             clinical chemistry, urinalysis, vital signs or 12 lead ECG at Visit 1, which may put&#xD;
             the volunteer at risk because of his participation in the study.&#xD;
&#xD;
         10. Use of drugs with enzyme inducing properties such as St John's Wort within 4 weeks&#xD;
             prior to the administration of the investigational product&#xD;
&#xD;
         11. Use of any other prescribed medicine and over the counter drugs within 2 week or 5&#xD;
             times the half life, whichever is longer prior to the administration of the&#xD;
             investigational product up to and including the follow up visit (Visit 4), with the&#xD;
             exception of occasional use of paracetamol or ibuprofen and over the counter&#xD;
             adrenergic nasal spray. No medications known to prolong the QT/corrected QT interval&#xD;
             are allowed.&#xD;
&#xD;
         12. Excessive intake of caffeine containing drinks or food&#xD;
&#xD;
         13. Any intake of grapefruit and Seville oranges including products containing grapefruit&#xD;
             or Seville oranges within 7 days of the admission on Day -1.&#xD;
&#xD;
         14. History of severe allergy/hypersensitivity or ongoing clinically important&#xD;
             allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar&#xD;
             chemical structure or class to Selumetinib.&#xD;
&#xD;
         15. Plasma donation within 1 month of screening (Visit 1) or any blood donation or blood&#xD;
             loss greater than 500 mL during the 3 months prior to screening (Visit 1).&#xD;
&#xD;
         16. History of or current alcohol or drug abuse.&#xD;
&#xD;
         17. A suspected or manifested infection according to the International Air Transport&#xD;
             Association Categories A and B infectious substances.&#xD;
&#xD;
         18. Positive results on screening tests for HIV and/or hepatitis B and/or hepatitis C.&#xD;
&#xD;
         19. Baseline LVEF &lt;55% measured by echocardiography.&#xD;
&#xD;
         20. Planned inpatient surgery, dental procedure or hospitalisation during the study.&#xD;
&#xD;
         21. Healthy male volunteers who in the opinion of the Principal Investigator, should not&#xD;
             participate in the study.&#xD;
&#xD;
         22. Judgment by Principal Investigator that the volunteer should not participate in the&#xD;
             study if they have ongoing or recent minor medical complaints that may interfere with&#xD;
             the interpretation of study data or are considered unlikely to comply with study&#xD;
             procedures, restrictions, and requirements.&#xD;
      </textblock>
    </criteria>
    <gender>Male</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>Stuart Mair</last_name>
    <role>Principal Investigator</role>
    <affiliation>Quotient Clinical Ltd</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nottingham</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>March 2016</verification_date>
  <study_first_submitted>August 8, 2014</study_first_submitted>
  <study_first_submitted_qc>September 10, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 12, 2014</study_first_posted>
  <results_first_submitted>October 6, 2015</results_first_submitted>
  <results_first_submitted_qc>March 4, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">April 5, 2016</results_first_posted>
  <last_update_submitted>March 4, 2016</last_update_submitted>
  <last_update_submitted_qc>March 4, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">April 5, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>bioavailability</keyword>
  <keyword>pharmacokinetics</keyword>
  <keyword>I phase</keyword>
  <keyword>AZD6244</keyword>
  <keyword>cancer</keyword>

  <clinical_results>

    <participant_flow>
      <recruitment_details>21 subjects were enrolled, 12 of these subjects went on to receive treatment</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Selumetinib</title>
          <description>Patients received a single oral dose of selumetinib 75mg followed by IV carbon 14 selumetinib (80 micrograms) 1 hour 15 minutes after receiving the oral dose.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Subjects Treated</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Selumetinib</title>
          <description>Patients received a single oral dose of selumetinib 75mg followed by IV carbon 14 selumetinib (80 micrograms) 1 hour 15 minutes after receiving the oral dose.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="42" spread="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Absolute Bioavailability</title>
        <description>To calculate absolute bioavailability we used the formula: Area Under the Curve (oral dose)/Area Under the Curve (intravenous dose)*100</description>
        <time_frame>0 to 72 hours post-dose</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Selumetinib</title>
            <description>Selumetinib 75 mg oral followed by IV carbon 14 selumetinib (80 micrograms) administered 1 hour 15 minutes after the oral dose.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Bioavailability</title>
          <description>To calculate absolute bioavailability we used the formula: Area Under the Curve (oral dose)/Area Under the Curve (intravenous dose)*100</description>
          <units>% of bioavailability</units>
          <param>Geometric Mean</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.1" lower_limit="60.1" upper_limit="64.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Selumetinib</title>
          <description>Patients received a single oral dose of selumetinib 75mg followed by IV carbon 14 selumetinib (80 micrograms) 1 hour 15 minutes after receiving the oral dose.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Head Ache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Acne</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="12"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Gabriella Mariani</name_or_title>
      <organization>AstraZeneca</organization>
      <phone>+44 7818 523 899</phone>
      <email>ClinicalTrialTransparency@astrazeneca.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02238782
org study id: D1532C00080
nct id: NCT02238782
lead sponsor: 
has dmc: No
To assess the absolute bioavailability of oral selumetinib in healthy male volunteers
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Absolute Bioavailability
time frame: 0 to 72 hours post-dose
description: To calculate absolute bioavailability we used the formula: Area Under the Curve (oral dose)/Area Under the Curve (intravenous dose)*100
arm group label: selumetinib 75mg single dose
arm group type: Experimental
description: 3 capsules of 25 mg administered orally
intervention type: Drug
intervention name: selumetinib 75mg single dose
description: 3 capsules of 25 mg given as a single dose
arm group label: selumetinib 75mg single dose
other name: Selumetinib
intervention type: Other
intervention name: [14C] selumetinib IV solution
description: single, radiolabeled, IV (infused), microdose (80 μg) of [14C] selumetinib, infused using a syringe pump as a 15-minute infusion, administered 1h 15 min after receiving the oral dose
arm group label: selumetinib 75mg single dose
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Stuart Mair
role: Principal Investigator
affiliation: Quotient Clinical Ltd
facility: 
country: United Kingdom
responsible party type: Sponsor
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 