<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/NCT02256748</url>
  </required_header>
  <id_info>
    <org_study_id>1206.9</org_study_id>
    <nct_id>NCT02256748</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers</brief_title>
  <official_title>A Study to Evaluate the Effect of Multiple Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Midazolam in Healthy Male Volunteers</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 objective of the study was to investigate the effect of BIRT 2584 XX and its metabolite&#xD;
      BI 610100 when BIRT 2584 XX is administered as a tablet to near steady state in estimated&#xD;
      high therapeutic dose on the pharmacokinetics (PK) of midazolam, a probe substrate for&#xD;
      CYP3A4. The PK of midazolam was measured before dosing of BIRT 2584 XX, after a single dose&#xD;
      of BIRT 2584 XX and after repeated doses of BIRT 2584 XX for 3 and 12 days&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2005</start_date>
  <primary_completion_date type="Actual">August 2005</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-∞ of midazolam (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 13 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of midazolam (maximum concentration of midazolam in plasma)</measure>
    <time_frame>up to 13 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ of 1'-hydroxymidazolam (area under the concentration-time curve of 1'-hydroxymidazolam in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 13 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax of 1'-hydroxymidazolam (maximum concentration of 1'-hydroxymidazolam in plasma)</measure>
    <time_frame>up to 13 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ ratio of 1'-hydroxymidazolam to midazolam</measure>
    <time_frame>up to 13 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analytes in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to the maximum concentration of the analytes in plasma)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant of the analytes in plasma)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of the analytes in plasma)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTpo (mean residence time of the analytes in the body after po administration)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of the analytes in the plasma after extravascular administration)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose)</measure>
    <time_frame>up to 13 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose levels of BIRT 2584 XX and BI 610100</measure>
    <time_frame>days 1, 3 and 12</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal findings in physical examination</measure>
    <time_frame>up to 29 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 29 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant changes in 12-lead ECG</measure>
    <time_frame>up to 29 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with clinically significant changes in vital signs</measure>
    <time_frame>up to 29 days</time_frame>
    <description>Pulse rate, systolic, and diastolic blood pressure</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 44 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Day 29</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BIRT 2584 XX + Midazolam</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BIRT 2584 XX: Multiple doses for 12 days (bid on days 1 and 2, qd from days 3 to 12)&#xD;
Midazolam: Administration on days -2, 1, 3, and 12</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRT 2584 XX</intervention_name>
    <arm_group_label>BIRT 2584 XX + Midazolam</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam</intervention_name>
    <arm_group_label>BIRT 2584 XX + Midazolam</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male subjects as determined by results of the screening&#xD;
&#xD;
          -  Signed written informed consent in accordance with Good Clinical Practice (GCP) and&#xD;
             local legislation&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 55 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and ≤ 29.9 kg/m2&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding during the medical examination (including blood pressure, pulse rate, and&#xD;
             electrocardiogram) deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic,&#xD;
             hematological, oncological, or hormonal disorders&#xD;
&#xD;
          -  Surgery of gastrointestinal tract (except appendectomy)&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          -  Relevant history of orthostatic hypotension, fainting spells, or blackouts&#xD;
&#xD;
          -  Chronic or relevant acute infections&#xD;
&#xD;
          -  History of allergy/hypersensitivity (including drug allergy) considered relevant to&#xD;
             the trial as judged by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (greater than 24 hours) (less than 1 month prior&#xD;
             to administration or during the trial)&#xD;
&#xD;
          -  Use of any drugs, which might influence the results of the trial (less than 10 days&#xD;
             prior to study drug administration or expected during the trial)&#xD;
&#xD;
          -  Participation in another trial with an investigational drug (less than 2 months prior&#xD;
             to administration or expected during trial)&#xD;
&#xD;
          -  Smoker (more than 10 cigarettes/day or more than 3 cigars/day or more than 3&#xD;
             pipes/day)&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g of ethanol per day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation or loss greater than 400 mL (less than 1 month prior to administration&#xD;
             or expected during the trial)&#xD;
&#xD;
          -  Clinically relevant laboratory abnormalities&#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>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>October 2, 2014</study_first_submitted>
  <study_first_submitted_qc>October 2, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 6, 2014</study_first_posted>
  <last_update_submitted>October 2, 2014</last_update_submitted>
  <last_update_submitted_qc>October 2, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 6, 2014</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>Midazolam</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02256748
org study id: 1206.9
nct id: NCT02256748
lead sponsor: 
The objective of the study was to investigate the effect of BIRT 2584 XX and its metabolite
      BI 610100 when BIRT 2584 XX is administered as a tablet to near steady state in estimated
      high therapeutic dose on the pharmacokinetics (PK) of midazolam, a probe substrate for
      CYP3A4. The PK of midazolam was measured before dosing of BIRT 2584 XX, after a single dose
      of BIRT 2584 XX and after repeated doses of BIRT 2584 XX for 3 and 12 days
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-∞ of midazolam (area under the concentration-time curve of midazolam in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 13 days
measure: Cmax of midazolam (maximum concentration of midazolam in plasma)
time frame: up to 13 days
measure: AUC0-∞ of 1'-hydroxymidazolam (area under the concentration-time curve of 1'-hydroxymidazolam in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 13 days
measure: Cmax of 1'-hydroxymidazolam (maximum concentration of 1'-hydroxymidazolam in plasma)
time frame: up to 13 days
measure: AUC0-∞ ratio of 1'-hydroxymidazolam to midazolam
time frame: up to 13 days
measure: AUC0-tz (area under the concentration-time curve of the analytes in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 13 days
measure: tmax (time from dosing to the maximum concentration of the analytes in plasma)
time frame: up to 13 days
measure: λz (terminal rate constant of the analytes in plasma)
time frame: up to 13 days
measure: t1/2 (terminal half-life of the analytes in plasma)
time frame: up to 13 days
measure: MRTpo (mean residence time of the analytes in the body after po administration)
time frame: up to 13 days
measure: CL/F (apparent clearance of the analytes in the plasma after extravascular administration)
time frame: up to 13 days
measure: Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose)
time frame: up to 13 days
measure: Pre-dose levels of BIRT 2584 XX and BI 610100
time frame: days 1, 3 and 12
measure: Number of subjects with abnormal findings in physical examination
time frame: up to 29 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 29 days
measure: Number of subjects with clinically significant changes in 12-lead ECG
time frame: up to 29 days
measure: Number of subjects with clinically significant changes in vital signs
time frame: up to 29 days
description: Pulse rate, systolic, and diastolic blood pressure
measure: Number of subjects with adverse events
time frame: up to 44 days
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Day 29
arm group label: BIRT 2584 XX + Midazolam
arm group type: Experimental
description: BIRT 2584 XX: Multiple doses for 12 days (bid on days 1 and 2, qd from days 3 to 12)
Midazolam: Administration on days -2, 1, 3, and 12
intervention type: Drug
intervention name: BIRT 2584 XX
arm group label: BIRT 2584 XX + Midazolam
intervention type: Drug
intervention name: Midazolam
arm group label: BIRT 2584 XX + Midazolam
criteria: 
gender: Male
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Midazolam