<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/NCT02999191</url>
  </required_header>
  <id_info>
    <org_study_id>1386.17</org_study_id>
    <secondary_id>2016-001534-97</secondary_id>
    <nct_id>NCT02999191</nct_id>
  </id_info>
  <brief_title>Relative Bioavailability of BI 1467335 Tablet and Oral Solution, and Food Effect on Tablet in Healthy Male Subjects</brief_title>
  <official_title>Relative Bioavailability of a BI 1467335 Tablet Compared to a BI 1467335 Oral Solution and the Effect of Food on the Bioavailability of the Tablet Following Oral Administration (a Randomised, Open-label, Single Dose, Three-way Crossover Trial in Healthy Male Subjects)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      The primary objective of this trial is to investigate the relative bioavailability of BI&#xD;
      1467335, given as film-coated tablet compared to BI 1467335, given as oral solution. This&#xD;
      assessment will be performed under fasted conditions. Furthermore, the effect of food on&#xD;
      relative bioavailability of the tablet formulation of BI 1467335 will be investigated.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2017</start_date>
  <completion_date type="Actual">April 10, 2017</completion_date>
  <primary_completion_date type="Actual">March 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>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-tz of BI 1467335</measure>
    <time_frame>At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.</time_frame>
    <description>This outcome measure presents AUC0-tz [area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point].</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of BI 1467335</measure>
    <time_frame>At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.</time_frame>
    <description>This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Healthy Volunteers</condition>
  <arm_group>
    <arm_group_label>BI 1467335 (Treatment A)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet under fasted conditions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1467335 (Treatment B)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Oral solution under fasted conditions</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1467335 (Treatment C)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tablet under fed conditions</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1467335 (Treatment A)</intervention_name>
    <arm_group_label>BI 1467335 (Treatment A)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1467335 (Treatment B)</intervention_name>
    <arm_group_label>BI 1467335 (Treatment B)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1467335 (Treatment C)</intervention_name>
    <arm_group_label>BI 1467335 (Treatment C)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects according to the investigators assessment, based on a complete&#xD;
             medical history including a physical examination, vital signs (Blood Pressure&#xD;
             (BP),Pulse Rate(PR)), 12-lead Electrocardiogram (ECG), and clinical laboratory tests&#xD;
&#xD;
          -  Age of 18 to 55 years (incl.)&#xD;
&#xD;
          -  Body Mass Index (BMI) of 18.5 to 29.9 kg/m2 (incl.)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice (GCP) and local legislation&#xD;
&#xD;
          -  Willingness to comply with contraception requirements. Subjects who are sexually&#xD;
             active, must use, with their female partner, adequate contraception throughout the&#xD;
             study and until one month after the last administration of trial medication. Adequate&#xD;
             methods are:&#xD;
&#xD;
               -  Sexual abstinence or&#xD;
&#xD;
               -  A vasectomy performed at least 1 year prior to screening in combination with a&#xD;
                  barrier method (condom or diaphragm) or&#xD;
&#xD;
               -  Surgical sterilisation (including bilateral tubal occlusion, hysterectomy or&#xD;
                  bilateral oophorectomy) of the subjects female partner or&#xD;
&#xD;
               -  The use of condoms, if the female partner uses in addition an adequate&#xD;
                  contraception method, e.g., intrauterine device (IUD), hormonal contraception&#xD;
                  (e.g. implants, injectables, combined oral or vaginal contraceptives) that&#xD;
                  started at least 2 months prior to first drug administration, or barrier method&#xD;
                  (e.g. diaphragm with spermicide) Unprotected sexual intercourse with a pregnant&#xD;
                  female partner is not allowed throughout the study and until one month after the&#xD;
                  last administration of trial medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding in the medical examination (including Blood Pressure (BP), Pulse Rate (PR)&#xD;
             or Electrocardiogram (ECG) is deviating from normal and judged as clinically relevant&#xD;
             by the investigator&#xD;
&#xD;
          -  Repeated measurement of systolic blood pressure outside the range of 90 to 140 mmHg,&#xD;
             diastolic blood pressure outside the range of 50 to 90 mmHg, or pulse rate outside the&#xD;
             range of 50 to 90 beats per minute (bpm)&#xD;
&#xD;
          -  Any laboratory value outside the reference range that the investigator considers to be&#xD;
             of clinical relevance&#xD;
&#xD;
          -  Any evidence of a concomitant disease judged as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Cholecystectomy and/or surgery of the gastrointestinal tract that could interfere with&#xD;
             the pharmacokinetics of the trial medication (except appendectomy and simple hernia&#xD;
             repair)&#xD;
&#xD;
          -  Diseases of the central nervous system (including but not limited to any kind of&#xD;
             seizures or stroke), and other relevant neurological or psychiatric disorders&#xD;
&#xD;
          -  History of relevant orthostatic hypotension, fainting spells, or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of relevant allergy or hypersensitivity (including allergy to the trial&#xD;
             medication or its excipients)&#xD;
&#xD;
          -  Use of drugs within 30 days prior to administration of trial medication, if that might&#xD;
             reasonably influence the results of the trial (incl. QT/QTc interval prolongation)&#xD;
&#xD;
          -  Participation in another trial where an investigational drug has been administered&#xD;
             within 60 days prior to planned administration of trial medication or current&#xD;
             participation in another trial involving administration of investigational drug&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes or 3 cigars or 3 pipes per day)&#xD;
&#xD;
          -  Inability to refrain from smoking on specified trial days&#xD;
&#xD;
          -  Alcohol abuse (consumption of more than 30 g per day)&#xD;
&#xD;
          -  Drug abuse or positive drug screening&#xD;
&#xD;
          -  Blood donation of more than 100 mL within 30 days prior to administration of trial&#xD;
             medication or intended donation during the trial&#xD;
&#xD;
          -  Intention to perform excessive physical activities within 7 days prior to&#xD;
             administration of trial medication or during the trial&#xD;
&#xD;
          -  Inability to comply with dietary regimen of trial site&#xD;
&#xD;
          -  A marked baseline prolongation of QT/QTc interval (such as QTc intervals that are&#xD;
             repeatedly greater than 450 ms) or any other relevant ECG finding at screening&#xD;
&#xD;
          -  A history of additional risk factors for Torsades de Pointes (such as heart failure,&#xD;
             hypokalaemia, or family history of Long QT Syndrome)&#xD;
&#xD;
          -  Subject is assessed as unsuitable for inclusion by the investigator, for instance,&#xD;
             because considered not able to understand and comply with study requirements, or has a&#xD;
             condition that would not allow safe participation in the study&#xD;
&#xD;
        In addition, the following trial-specific exclusion criteria apply:&#xD;
&#xD;
        - Cataract in the medical history&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Humanpharmakologisches Zentrum Biberach</name>
      <address>
        <city>Biberach</city>
        <zip>88397</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <link>
    <url>http://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>December 19, 2016</study_first_submitted>
  <study_first_submitted_qc>December 19, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 21, 2016</study_first_posted>
  <results_first_submitted>May 11, 2021</results_first_submitted>
  <results_first_submitted_qc>May 11, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 7, 2021</results_first_posted>
  <last_update_submitted>May 11, 2021</last_update_submitted>
  <last_update_submitted_qc>May 11, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 12, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02999191/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 15, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT02999191/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study was randomised, open-label, single-dose, three-way crossover trial. 18 subjects entered in the study. 18 subjects were treated in Treatment A: BI 1467335 10 mg tablets, fasted. 18 subjects were treated in Treatment B: BI 1467335 10 mg oral solution, fasted and 17 subjects were treated in Treatment C: BI 1467335 10 mg tablets, fed.</recruitment_details>
      <pre_assignment_details>All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and none of the exclusion criteria.&#xD;
Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 1467335: Tablets, Fasted/Solution, Fasted/Tablets, Fed</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fasted state [Treatment A] in period 1, followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10 hours [h] [Treatment B] in period 2, then followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
        <group group_id="P2">
          <title>BI 1467335: Solution, Fasted/Tablets, Fed/Tablets, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast at least 10h [Treatment B] in period 1, followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 2, then followed by BI 1467335 10 mg [2*5 mg] film-coated tablets in the fasted state [Treatment A] orally with 240 mL of water after an overnight fast of at least 10h in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
        <group group_id="P3">
          <title>BI 1467335: Tablets, Fed/Tablets, Fasted/Solution, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 1, followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fasted state [Treatment A] in period 2, then followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h [Treatment B] in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1 [1 Day]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Wash-out Period 1 [21 Days]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Treatment Period 2 [1 Day]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Wash-out Period 2 [21 Days]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 3 [1 Day]</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="6"/>
                <participants group_id="P3" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set [TS]: All subjects who received at least one dose of study medication.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 1467335: Tablets, Fasted/Solution, Fasted/Tablets, Fed</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fasted state [Treatment A] in period 1, followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10 hours [h] [Treatment B] in period 2, then followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
        <group group_id="B2">
          <title>BI 1467335: Solution, Fasted/Tablets, Fed/Tablets, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast at least 10h [Treatment B] in period 1, followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 2, then followed by BI 1467335 10 mg [2*5 mg] film-coated tablets in the fasted state [Treatment A] orally with 240 mL of water after an overnight fast of at least 10h in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
        <group group_id="B3">
          <title>BI 1467335: Tablets, Fed/Tablets, Fasted/Solution, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state [Treatment C] in period 1, followed by BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fasted state [Treatment A] in period 2, then followed by BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h [Treatment B] in period 3. The treatment duration was one day for each treatment [3 single doses], separated by washout phases of at least 21 days.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="18"/>
          </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="42.2" spread="12.2"/>
                    <measurement group_id="B2" value="45.7" spread="9.8"/>
                    <measurement group_id="B3" value="45.7" spread="6.3"/>
                    <measurement group_id="B4" value="44.5" spread="9.3"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="17"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC0-tz of BI 1467335</title>
        <description>This outcome measure presents AUC0-tz [area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point].</description>
        <time_frame>At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.</time_frame>
        <population>PharmacoKinetic Set [PKS]: This subject set included all subjects in the Treated Set [All subjects who received at least one dose of study medication] who provided at least one primary PK parameter that was not excluded due to a relevant protocol violation [PV] or non-evaluable plasma concentrations. One subject did not receive the dose in period 2 [Tablets, fed].</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1467335: Tablets, Fed</title>
            <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state. The treatment duration was one day.</description>
          </group>
          <group group_id="O2">
            <title>BI 1467335: Tablets, Fasted</title>
            <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.</description>
          </group>
          <group group_id="O3">
            <title>BI 1467335: Solution, Fasted</title>
            <description>The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-tz of BI 1467335</title>
          <description>This outcome measure presents AUC0-tz [area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point].</description>
          <population>PharmacoKinetic Set [PKS]: This subject set included all subjects in the Treated Set [All subjects who received at least one dose of study medication] who provided at least one primary PK parameter that was not excluded due to a relevant protocol violation [PV] or non-evaluable plasma concentrations. One subject did not receive the dose in period 2 [Tablets, fed].</population>
          <units>nanomole*hour/Liter (nmol*h/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.90" spread="90.5"/>
                    <measurement group_id="O2" value="2.24" spread="101"/>
                    <measurement group_id="O3" value="2.49" spread="121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The statistical model used for the analysis of the endpoint was an ANOVA [Analysis of Variance] model on the logarithmic scale. This model included effects accounting for the following sources of variation: 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>89.90</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>36.0</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>73.304</ci_lower_limit>
            <ci_upper_limit>110.25</ci_upper_limit>
            <estimate_desc>The estimated parameter was the adjusted geometric mean ratios [%] of BI 1467335: Tablets, fasted (numerator) and Solution, fasted (denominator). The Standard Deviation [SD] is the intra-individual geometric coefficient of variation [%].</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The statistical model used for the analysis of the endpoint was an ANOVA [Analysis of Variance] model on the logarithmic scale. This model included effects accounting for the following sources of variation: 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>170.78</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>33.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>139.85</ci_lower_limit>
            <ci_upper_limit>208.54</ci_upper_limit>
            <estimate_desc>The estimated parameter was the adjusted geometric mean ratios [%] of BI 1467335: Tablets, fed (numerator) and Tablets, fasted (denominator). The parameter dispersion type [SD] is the intra-individual geometric coefficient of variation [%].</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax of BI 1467335</title>
        <description>This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).</description>
        <time_frame>At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.</time_frame>
        <population>PharmacoKinetic Set [PKS]: This subject set included all subjects in the Treated Set [All subjects who received at least one dose of study medication] who provided at least one primary PK parameter that was not excluded due to a relevant protocol violation [PV] or non-evaluable plasma concentrations. One subject did not receive the dose in period 2 [Tablets, Fed].</population>
        <group_list>
          <group group_id="O1">
            <title>BI 1467335: Tablets, Fed</title>
            <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state. The treatment duration was one day.</description>
          </group>
          <group group_id="O2">
            <title>BI 1467335: Tablets, Fasted</title>
            <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.</description>
          </group>
          <group group_id="O3">
            <title>BI 1467335: Solution, Fasted</title>
            <description>The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax of BI 1467335</title>
          <description>This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).</description>
          <population>PharmacoKinetic Set [PKS]: This subject set included all subjects in the Treated Set [All subjects who received at least one dose of study medication] who provided at least one primary PK parameter that was not excluded due to a relevant protocol violation [PV] or non-evaluable plasma concentrations. One subject did not receive the dose in period 2 [Tablets, Fed].</population>
          <units>nanomole/Liter (nmol/L)</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="17"/>
                <count group_id="O2" value="18"/>
                <count group_id="O3" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.55" spread="120"/>
                    <measurement group_id="O2" value="1.85" spread="107"/>
                    <measurement group_id="O3" value="2.20" spread="126"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The statistical model used for the analysis of the endpoint was an ANOVA [Analysis of Variance] model on the logarithmic scale. This model included effects accounting for the following sources of variation: 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>84.17</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>48.8</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>64.260</ci_lower_limit>
            <ci_upper_limit>110.24</ci_upper_limit>
            <estimate_desc>The estimated parameter was the adjusted geometric mean ratios [%] of BI 1467335: Tablets, fasted (numerator) and Solution, fasted (denominator). The parameter dispersion type [SD] is the intra-individual geometric coefficient of variation [%].</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>The statistical model used for the analysis of the endpoint was an ANOVA [Analysis of Variance] model on the logarithmic scale. This model included effects accounting for the following sources of variation: 'sequence', 'subjects nested within sequences', 'period' and 'treatment'. The effect 'subjects within sequences' was considered as random, whereas the other effects were considered as fixed.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Ratio</param_type>
            <param_value>136.16</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>54.8</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>99.885</ci_lower_limit>
            <ci_upper_limit>185.61</ci_upper_limit>
            <estimate_desc>The estimated parameter was the adjusted geometric mean ratios [%] of BI 1467335: Tablets, fed (numerator) and Tablets, fasted (denominator). The parameter dispersion type [SD] is the intra-individual geometric coefficient of variation [%].</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the first day of study drug administration until 21 days after the first drug administration, up to 22 days.</time_frame>
      <desc>Treated set [TS]: All subjects who received at least one dose of study medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 1467335: Tablets, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day.</description>
        </group>
        <group group_id="E2">
          <title>BI 1467335: Solution, Fasted</title>
          <description>The subjects were administered BI 1467335 10 mg oral solution in the fasted state orally with 240 mL of water after an overnight fast of at least 10h. The treatment duration was one day</description>
        </group>
        <group group_id="E3">
          <title>BI 1467335: Tablets, Fed</title>
          <description>The subjects were administered BI 1467335 10 mg [2*5 mg] film-coated tablets orally in the fed state. The treatment duration was one day.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 20.0</default_vocab>
        <default_assessment>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="18"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Viral upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Joint injury</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Musculoskeletal stiffness</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
              <event>
                <sub_title>Rhinitis allergic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="18"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="18"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="17"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Boehringer Ingelheim, Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.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/NCT02999191
org study id: 1386.17
secondary id: 2016-001534-97
nct id: NCT02999191
lead sponsor: 
The primary objective of this trial is to investigate the relative bioavailability of BI
      1467335, given as film-coated tablet compared to BI 1467335, given as oral solution. This
      assessment will be performed under fasted conditions. Furthermore, the effect of food on
      relative bioavailability of the tablet formulation of BI 1467335 will be investigated.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-tz of BI 1467335
time frame: At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.
description: This outcome measure presents AUC0-tz [area under the concentration-time curve of BI 1467335 in plasma over the time interval from 0 to the last quantifiable data point].
measure: Cmax of BI 1467335
time frame: At -1:00h [hours (h): minutes (min)] before drug administration and at 0:15, 0:30, 0:45, 1:00, 1:15, 1:30, 1:45, 2:00, 2:30, 3:00, 4:00, 6:00, 8:00, 10:00, 12:00 and 24:00 h:min after drug administration.
description: This outcome measure presents the maximum measured concentration of BI 1467335 in plasma (Cmax of BI 1467335).
arm group label: BI 1467335 (Treatment A)
arm group type: Experimental
description: Tablet under fasted conditions
arm group label: BI 1467335 (Treatment B)
arm group type: Experimental
description: Oral solution under fasted conditions
arm group label: BI 1467335 (Treatment C)
arm group type: Experimental
description: Tablet under fed conditions
intervention type: Drug
intervention name: BI 1467335 (Treatment A)
arm group label: BI 1467335 (Treatment A)
intervention type: Drug
intervention name: BI 1467335 (Treatment B)
arm group label: BI 1467335 (Treatment B)
intervention type: Drug
intervention name: BI 1467335 (Treatment C)
arm group label: BI 1467335 (Treatment C)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
country: Germany
url: http://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 