<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/NCT03782987</url>
  </required_header>
  <id_info>
    <org_study_id>1407-0014</org_study_id>
    <secondary_id>2018-003495-13</secondary_id>
    <nct_id>NCT03782987</nct_id>
  </id_info>
  <brief_title>A Study in Healthy Men to Test How Itraconazole Influences the Amount of BI 730357 in the Blood</brief_title>
  <official_title>Relative Bioavailability of a Single Oral Dose of BI 730357 When Administered Alone or in Combination With Multiple Oral Doses of Itraconazole in Healthy Male Subjects (an Open-label, One-way Crossover Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main objective of this trial is to investigate the relative bioavailability of BI 730357&#xD;
      in plasma when given as oral single dose together with multiple oral doses of itraconazole&#xD;
      (Test, T) as compared to when given alone as oral single dose (Reference, R)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 10, 2019</start_date>
  <completion_date type="Actual">March 11, 2019</completion_date>
  <primary_completion_date type="Actual">March 11, 2019</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)</measure>
    <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
    <description>AUC0-tz, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Measured Concentration of the BI 730357 in Plasma (Cmax)</measure>
    <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
    <description>Cmax, maximum measured concentration of the BI 730357 in plasma is presented here.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)</measure>
    <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
    <description>AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 730357 + Itraconazole (T)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 730357 (R)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 730357</intervention_name>
    <description>0 mg BI 730357 tablet orally on Day 1</description>
    <arm_group_label>BI 730357 (R)</arm_group_label>
    <arm_group_label>BI 730357 + Itraconazole (T)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Itraconazole</intervention_name>
    <description>20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</description>
    <arm_group_label>BI 730357 + Itraconazole (T)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects according to the assessment of the investigator, as based on a&#xD;
             complete 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 50 years (inclusive)&#xD;
&#xD;
          -  Body mass index (BMI) of 18.5 to 29.9 kg/m2 (inclusive)&#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;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding in the medical examination (including blood pressure (BP), pulse rate (PR)&#xD;
             or Electrocardiogram (ECG)) deviating from normal and assessed 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 45 to 90 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 assessed as clinically relevant by the&#xD;
             investigator&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Cholecystectomy or other surgery of the gastrointestinal tract that could interfere&#xD;
             with the pharmacokinetics of the trial medication (except appendectomy or simple&#xD;
             hernia 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 of planned administration of trial medication that might&#xD;
             reasonably influence the results of the trial (including drugs that cause QT/QTc&#xD;
             interval prolongation)&#xD;
&#xD;
          -  Intake of an investigational drug in another clinical trial within 60 days of planned&#xD;
             administration of investigational drug in the current trial, or concurrent&#xD;
             participation in another clinical trial in which investigational drug is administered&#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 of planned administration of trial&#xD;
             medication or intended blood donation during the trial&#xD;
&#xD;
          -  Intention to perform excessive physical activities within one week prior to the&#xD;
             administration of trial medication or during the trial&#xD;
&#xD;
          -  Inability to comply with the dietary regimen of the 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 Electrocardiogram (ECG) finding&#xD;
             at screening&#xD;
&#xD;
          -  A history of additional risk factors for Torsade 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 the subject is not considered able to understand and comply with study&#xD;
             requirements, or has a condition that would not allow safe participation in the study&#xD;
&#xD;
        In addition, the following trial-specific exclusion criteria apply:&#xD;
&#xD;
          -  Liver enzyme (ALT, AST, GGT) values above upper limit of normal at the screening&#xD;
             examination&#xD;
&#xD;
          -  History of drug-induced liver injury&#xD;
&#xD;
          -  History of heart failure, or any evidence of ventricular dysfunction in the history&#xD;
&#xD;
          -  History of hereditary fructose intolerance&#xD;
&#xD;
          -  Male subjects with WOCBP partner who are unwilling to use male contraception (condom&#xD;
             or sexual abstinence) from time point of first administration of trial medication&#xD;
             until 30 days after the last administration of trial medication&#xD;
&#xD;
          -  Further exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <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://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>December 19, 2018</study_first_submitted>
  <study_first_submitted_qc>December 19, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <results_first_submitted>August 12, 2022</results_first_submitted>
  <results_first_submitted_qc>August 12, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 12, 2023</results_first_posted>
  <last_update_submitted>August 12, 2022</last_update_submitted>
  <last_update_submitted_qc>August 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Itraconazole</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:&#xD;
1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: http://trials.boehringer-ingelheim.com/</ipd_description>
  </patient_data>
  <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>February 20, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03782987/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>April 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03782987/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This was an open-label, two-treatment, two-period, one-way crossover trial in healthy participants in order to compare the test treatment (T) to the reference treatment (R). All participants underwent treatment R in Period 1 (Visit 2) and treatment T in Period 2 (Visit 3). There was at least 10 days washout between the administrations of BI 730357.</recruitment_details>
      <pre_assignment_details>All participants were screened for eligibility to participate in the trial. Participants attended specialist site which would then ensured that all participants met all inclusion/exclusion criteria. Participants were not to be entered to trial if any one of the specific entry criteria were not met.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>BI 730357 Alone/ BI 730357+Itraconazole</title>
          <description>Participants were administered 50 milligram (mg) BI 730357 tablet orally on Day 1 alone in treatment period 1 (R) and along with 20 milliliter (mL) of 10 mg/ mL Itraconazole oral solution on Day 1 of treatment period 2 (T). Itraconazole was administered once daily on Day -3, -2, -1 and 1 before administration of BI 730357 and on Day 2 to 9 in treatment period 2 only. There was a washout interval of at least 10 days between the administrations of BI 730357.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Period 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Washout Period</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Period 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
              </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>
      <population>Treated set (TS): The TS included all subjects who received at least 1 dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>BI 730357 Alone/ BI 730357+Itraconazole</title>
          <description>Participants were administered 50 milligram (mg) BI 730357 tablet orally on Day 1 alone in treatment period 1 (R) and along with 20 milliliter (mL) of 10 mg/ mL Itraconazole oral solution on Day 1 of treatment period 2 (T). Itraconazole was administered once daily on Day -3, -2, -1 and 1 before administration of BI 730357 and on Day 2 to 9 in treatment period 2 only. There was a washout interval of at least 10 days between the administrations of BI 730357.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
          </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="37.8" spread="8.3"/>
                  </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_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </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_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)</title>
        <description>AUC0-tz, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented.</description>
        <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
        <population>Pharmacokinetic (PK) parameter set (PKS): The PKS included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded due to relevant protocol deviations or due to PK non-evaluability.</population>
        <group_list>
          <group group_id="O1">
            <title>BI 730357 + Itraconazole (T)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</description>
          </group>
          <group group_id="O2">
            <title>BI 730357 (R)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)</title>
          <description>AUC0-tz, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented.</description>
          <population>Pharmacokinetic (PK) parameter set (PKS): The PKS included all subjects of the TS who provided at least 1 primary or secondary PK parameter that was not excluded due to relevant protocol deviations or due to PK non-evaluability.</population>
          <units>Nanomole* hour/ Litre (nmol*h/ L)</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43239.08" spread="NA">Standard Error is Geometric standard error (gSE) = 1.09</measurement>
                    <measurement group_id="O2" value="6657.49" spread="NA">Standard Error is Geometric standard error (gSE) = 1.09</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>Geometric mean (gMean) ratio (%) (T/ R)</param_type>
            <param_value>649.48</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>27.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>541.29</ci_lower_limit>
            <ci_upper_limit>779.29</ci_upper_limit>
            <estimate_desc>Confidence intervals were calculated based on the residual error from the ANOVA. Standard error of the mean is actually intra-individual geometric coefficient of variance (gCV).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Maximum Measured Concentration of the BI 730357 in Plasma (Cmax)</title>
        <description>Cmax, maximum measured concentration of the BI 730357 in plasma is presented here.</description>
        <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>BI 730357 + Itraconazole (T)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</description>
          </group>
          <group group_id="O2">
            <title>BI 730357 (R)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Measured Concentration of the BI 730357 in Plasma (Cmax)</title>
          <description>Cmax, maximum measured concentration of the BI 730357 in plasma is presented here.</description>
          <population>PKS</population>
          <units>nmol/ L</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="311.01" spread="NA">Standard Error is Geometric standard error (gSE) = 1.07</measurement>
                    <measurement group_id="O2" value="186.36" spread="NA">Standard Error is Geometric standard error (gSE) = 1.07</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>gMean ratio (%) (T/ R)</param_type>
            <param_value>166.88</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>17.7</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>148.42</ci_lower_limit>
            <ci_upper_limit>187.64</ci_upper_limit>
            <estimate_desc>Confidence intervals were calculated based on the residual error from the ANOVA. Standard error of the mean is actually intra-individual geometric coefficient of variance (gCV).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)</title>
        <description>AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here.</description>
        <time_frame>Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.</time_frame>
        <population>PKS</population>
        <group_list>
          <group group_id="O1">
            <title>BI 730357 + Itraconazole (T)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</description>
          </group>
          <group group_id="O2">
            <title>BI 730357 (R)</title>
            <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).</description>
          </group>
        </group_list>
        <measure>
          <title>Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)</title>
          <description>AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here.</description>
          <population>PKS</population>
          <units>nmol*h/ L</units>
          <param>Geometric Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="64934.55" spread="NA">Standard Error is Geometric standard error (gSE) = 1.10</measurement>
                    <measurement group_id="O2" value="6971.67" spread="NA">Standard Error is Geometric standard error (gSE) = 1.10</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Statistical model was an analysis of variance (ANOVA) on the logarithmic scale including 'subjects' as random effect and 'treatment' as fixed effect.</groups_desc>
            <non_inferiority_type>Other</non_inferiority_type>
            <param_type>gMean ratio (%) (T/ R)</param_type>
            <param_value>931.41</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>25.9</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>785.19</ci_lower_limit>
            <ci_upper_limit>1104.85</ci_upper_limit>
            <estimate_desc>Confidence intervals were calculated based on the residual error from the ANOVA. Standard error of the mean is actually intra-individual geometric coefficient of variance (gCV).</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>BI 730357: From first administration of BI 730357, up to 168 hours. Itraconazole: From first administration of itraconazole until second administration of BI 730357, up to 73 hours. BI 730357+ Itraconazole: From second administration of BI 730357 until 216 hours after the last administration of itraconazole, up to 18 days.</time_frame>
      <desc>Treated set (TS): The TS included all subjects who received at least 1 dose of trial medication.</desc>
      <group_list>
        <group group_id="E1">
          <title>BI 730357 (R)</title>
          <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).</description>
        </group>
        <group group_id="E2">
          <title>Itraconazole</title>
          <description>Participants were administered Itraconazole oral solution once daily on Day -3 to Day 1 before administration of 50 mg BI 730357 and on Day 2 to 9 after administration of BI 730357 in treatment period 2 only (T).</description>
        </group>
        <group group_id="E3">
          <title>BI 730357 + Itraconazole (T)</title>
          <description>Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.</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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 21.1</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="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Vessel puncture site pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Seasonal allergy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Presyncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="14"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="14"/>
              </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 Centre</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</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/NCT03782987
org study id: 1407-0014
secondary id: 2018-003495-13
nct id: NCT03782987
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
The main objective of this trial is to investigate the relative bioavailability of BI 730357
      in plasma when given as oral single dose together with multiple oral doses of itraconazole
      (Test, T) as compared to when given alone as oral single dose (Reference, R)
allocation: Non-Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 to the Last Quantifiable Data Point (AUC0-tz)
time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
description: AUC0-tz, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 to the last quantifiable data point is presented.
measure: Maximum Measured Concentration of the BI 730357 in Plasma (Cmax)
time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
description: Cmax, maximum measured concentration of the BI 730357 in plasma is presented here.
measure: Area Under the Concentration-time Curve of the BI 730357 in Plasma Over the Time Interval From 0 Extrapolated to Infinity (AUC0-∞)
time frame: Pharmacokinetic samples were taken within 3 hours (h) before administration of BI 730357 and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 34, 47, 71, 119 and 167 h in both periods and additionally at 215 and 263 h only for period 2.
description: AUC0-∞, area under the concentration-time curve of the BI 730357 in plasma over the time interval from 0 extrapolated to infinity is presented here.
arm group label: BI 730357 + Itraconazole (T)
arm group type: Experimental
description: Participants were administered 50 mg BI 730357 tablet orally on Day 1 along with 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.
arm group label: BI 730357 (R)
arm group type: Experimental
description: Participants were administered 50 mg BI 730357 tablet orally on Day 1 alone in treatment period 1 (R).
intervention type: Drug
intervention name: BI 730357
description: 0 mg BI 730357 tablet orally on Day 1
arm group label: BI 730357 (R)
arm group label: BI 730357 + Itraconazole (T)
intervention type: Drug
intervention name: Itraconazole
description: 20 mL of 10 mg/ mL Itraconazole oral solution in treatment period 2 only (T). Itraconazole was administered once daily for 12 days from Day -3 to Day 9.
arm group label: BI 730357 + Itraconazole (T)
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Germany
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Itraconazole
sharing ipd: No
ipd description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. studies conducted in a single center or targeting rare diseases (because of limitations with anonymization). For more details refer to: http://trials.boehringer-ingelheim.com/
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 