<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/NCT02256813</url>
  </required_header>
  <id_info>
    <org_study_id>1206.10</org_study_id>
    <nct_id>NCT02256813</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect of Multiple Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Warfarin, Omeprazole, Caffeine, and Dextromethorphan 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 Warfarin, Omeprazole, Caffeine, and Dextromethorphan Dosed Orally and Midazolam Dosed IV, 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 study aimed to investigate the effect of BIRT 2584 XX and its metabolite BI 610100 on the&#xD;
      Pharmacokinetics (PK) of five probe substrates for cytochrome P450 isozymes.&#xD;
&#xD;
      The substrates used to monitor enzyme activity were oral warfarin (for CYP2C9), oral&#xD;
      omeprazole (for CYP2C19), oral dextromethorphan (for CYP2D6), oral caffeine (for CYP1A2) and&#xD;
      intravenous midazolam (for hepatic CYP3A)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2005</start_date>
  <primary_completion_date type="Actual">December 2005</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>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC0-inf (Area under the concentration-time curve of midazolam IV and S-warfarin in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to day 19</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC (Area under the concentration-time curve of the ratio of omeprazole to 5-hydroxyomeprazole in plasma)</measure>
    <time_frame>up to day 19</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>0-12 hr urinary molar ratio of caffeine metabolites (1-Methylxanthine + 1-Methylurate +5-Acetylamino-6-formylamino-3-methyluracil)/ 1,7-Dimethylurate</measure>
    <time_frame>up to 12 hours after administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>0-12 hr urinary dextromethorphan/dextrorphan ratio</measure>
    <time_frame>up to 12 hours after administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (Area under the concentration-time curve of the S-warfarin, omeprazole and midazolam IV in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (Maximum measured concentration of the S-warfarin, omeprazole and midazolam IV in plasma)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (Time from dosing to the maximum concentration of the S-warfarin, omeprazole and midazolam IV in plasma)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRT (Mean residence time of the S-warfarin, omeprazole and midazolam IV in the body after administration)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (Apparent clearance of the S-warfarin, omeprazole and midazolam IV in plasma after extravascular single dose administration)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (Apparent volume of distribution during the terminal phase λz following extravascular administration S-warfarin, omeprazole and midazolam IV)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf (Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>trough levels of BIRT 2584 XX and BI 610100</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>approximate peak levels of BIRT 2584 XX and BI 610100</measure>
    <time_frame>up to day 19</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 48 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 48 days</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 + PK-cocktail</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRT 2584 XX</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Warfarin sodium</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Coumadin®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Omeprazole</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Omeprazole-ratiopharm® NT</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dextromethorphan hydrobromide</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Hustenstiller-ratiopharm®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Caffeine</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Coffeinum®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Midazolam hydrochloride</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Dormicum®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin K1</intervention_name>
    <arm_group_label>BIRT 2584 XX + PK-cocktail</arm_group_label>
    <other_name>Konakion®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  age ≥ 18 and ≤55 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and ≤ 29.9 kg/m2&#xD;
&#xD;
          -  healthy male subjects as determined by the investigator on the basis of medical&#xD;
             history, physical examination, clinical laboratory test results, vital signs, and&#xD;
             12-lead ECG at the screening visit&#xD;
&#xD;
          -  signed written informed consent in accordance with Good Clinical Practice (GCP) and&#xD;
             local legislation&#xD;
&#xD;
          -  non-smoker (a subject is considered to be a non-smoker if he has never smoked or has&#xD;
             stopped smoking ≥ 6 months before the screening visit)&#xD;
&#xD;
          -  agree not to take any prescription medications or non-prescription drugs (including&#xD;
             herbal preparations and vitamins) without approval by the investigator and not to&#xD;
             receive vaccinations during the course of the study&#xD;
&#xD;
          -  agree not to eat oranges, grapefruits, broccoli, Brussels sprouts, or char grilled&#xD;
             meats and not to drink grapefruit juice during the course of the study&#xD;
&#xD;
          -  agree not to drink alcoholic beverages during the course of the study&#xD;
&#xD;
          -  agree not to drink or eat caffeine and theobromine containing beverages and foods&#xD;
             during the course of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  any finding of the medical examination (including Blood Pressure, Pulse Rate, and ECG)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  gastrointestinal, hepatic, renal, respiratory (e.g. asthma), cardiovascular,&#xD;
             metabolic, immunologic, haematological, oncological, or hormonal disorders&#xD;
&#xD;
          -  any surgical or medical condition that could interfere with the administration of the&#xD;
             study drug or interpretation of the study results&#xD;
&#xD;
          -  diseases of the Central nervous system (CNS) (such as epilepsy) or psychiatric&#xD;
             disorders or 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;
          -  immunisation during the 2 weeks prior to the screening visit&#xD;
&#xD;
          -  known intolerance to benzodiazepines&#xD;
&#xD;
          -  known intolerance to the active and/or inactive ingredients in caffeine, warfarin,&#xD;
             vitamin K1, omeprazole, or dextromethorphan&#xD;
&#xD;
          -  known acute angle-closure glaucoma&#xD;
&#xD;
          -  elevated prothrombin time as determined by Prothrombin time (INR) &gt; 1.3&#xD;
&#xD;
          -  intake of drugs with a long half-life (greater than 24 hrs) (less than one 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;
          -  use of chewing tobacco or nicotine replacement devices within 6 months before the&#xD;
             screening visit&#xD;
&#xD;
          -  participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  alcohol abuse (more than 60 g of ethanol per day)&#xD;
&#xD;
          -  blood donation or loss greater than 100 mL (less than one month prior to&#xD;
             administration 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>Vitamin K</mesh_term>
    <mesh_term>Vitamin K 1</mesh_term>
    <mesh_term>Midazolam</mesh_term>
    <mesh_term>Dextromethorphan</mesh_term>
    <mesh_term>Caffeine</mesh_term>
    <mesh_term>Omeprazole</mesh_term>
    <mesh_term>Warfarin</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/NCT02256813
org study id: 1206.10
nct id: NCT02256813
lead sponsor: 
The study aimed to investigate the effect of BIRT 2584 XX and its metabolite BI 610100 on the
      Pharmacokinetics (PK) of five probe substrates for cytochrome P450 isozymes.

      The substrates used to monitor enzyme activity were oral warfarin (for CYP2C9), oral
      omeprazole (for CYP2C19), oral dextromethorphan (for CYP2D6), oral caffeine (for CYP1A2) and
      intravenous midazolam (for hepatic CYP3A)
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-inf (Area under the concentration-time curve of midazolam IV and S-warfarin in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to day 19
measure: AUC (Area under the concentration-time curve of the ratio of omeprazole to 5-hydroxyomeprazole in plasma)
time frame: up to day 19
measure: 0-12 hr urinary molar ratio of caffeine metabolites (1-Methylxanthine + 1-Methylurate +5-Acetylamino-6-formylamino-3-methyluracil)/ 1,7-Dimethylurate
time frame: up to 12 hours after administration
measure: 0-12 hr urinary dextromethorphan/dextrorphan ratio
time frame: up to 12 hours after administration
measure: AUC0-tz (Area under the concentration-time curve of the S-warfarin, omeprazole and midazolam IV in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to day 19
measure: Cmax (Maximum measured concentration of the S-warfarin, omeprazole and midazolam IV in plasma)
time frame: up to day 19
measure: tmax (Time from dosing to the maximum concentration of the S-warfarin, omeprazole and midazolam IV in plasma)
time frame: up to day 19
measure: λz (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)
time frame: up to day 19
measure: t1/2 (Terminal rate constant of the S-warfarin, omeprazole and midazolam IV in plasma)
time frame: up to day 19
measure: MRT (Mean residence time of the S-warfarin, omeprazole and midazolam IV in the body after administration)
time frame: up to day 19
measure: CL/F (Apparent clearance of the S-warfarin, omeprazole and midazolam IV in plasma after extravascular single dose administration)
time frame: up to day 19
measure: Vz/F (Apparent volume of distribution during the terminal phase λz following extravascular administration S-warfarin, omeprazole and midazolam IV)
time frame: up to day 19
measure: AUC0-inf (Area under the concentration-time curve of omeprazole in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to day 19
measure: trough levels of BIRT 2584 XX and BI 610100
time frame: up to day 19
measure: approximate peak levels of BIRT 2584 XX and BI 610100
time frame: up to day 19
measure: Number of subjects with adverse events
time frame: up to 48 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 48 days
arm group label: BIRT 2584 XX + PK-cocktail
arm group type: Experimental
intervention type: Drug
intervention name: BIRT 2584 XX
arm group label: BIRT 2584 XX + PK-cocktail
intervention type: Drug
intervention name: Warfarin sodium
arm group label: BIRT 2584 XX + PK-cocktail
other name: Coumadin®
intervention type: Drug
intervention name: Omeprazole
arm group label: BIRT 2584 XX + PK-cocktail
other name: Omeprazole-ratiopharm® NT
intervention type: Drug
intervention name: Dextromethorphan hydrobromide
arm group label: BIRT 2584 XX + PK-cocktail
other name: Hustenstiller-ratiopharm®
intervention type: Drug
intervention name: Caffeine
arm group label: BIRT 2584 XX + PK-cocktail
other name: Coffeinum®
intervention type: Drug
intervention name: Midazolam hydrochloride
arm group label: BIRT 2584 XX + PK-cocktail
other name: Dormicum®
intervention type: Drug
intervention name: Vitamin K1
arm group label: BIRT 2584 XX + PK-cocktail
other name: Konakion®
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: Vitamin K
mesh term: Vitamin K 1
mesh term: Midazolam
mesh term: Dextromethorphan
mesh term: Caffeine
mesh term: Omeprazole
mesh term: Warfarin