<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/NCT02256878</url>
  </required_header>
  <id_info>
    <org_study_id>1206.12</org_study_id>
    <nct_id>NCT02256878</nct_id>
  </id_info>
  <brief_title>Study to Evaluate the Effect Single and Multiple Oral Doses of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Amitriptyline and Nortriptyline in Healthy Male and Female Subjects</brief_title>
  <official_title>A Study to Evaluate the Effect of a Single Oral Dose and Multiple Oral Doses of 500 mg of BIRT 2584 XX Tablets on the Pharmacokinetic Parameters of Amitriptyline and Nortriptyline in Healthy Male and Female 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 objective of the study was evaluate that there is no clinically relevant interaction&#xD;
      between amitriptyline (or its metabolite nortriptyline) and BIRT 2584 XX (or its metabolite&#xD;
      BI 610100) when BIRT 2584 XX is administered as a tablet formulation to near steady state in&#xD;
      an estimated high therapeutic dose. Pharmacokinetics (PK) of amitriptyline and nortriptyline&#xD;
      were measured before dosing of BIRT 2584 XX, after the first dose of BIRT 2584 XX, and after&#xD;
      repeated doses of BIRT 2584 XX near steady state&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2004</start_date>
  <primary_completion_date type="Actual">November 2006</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-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 15 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-∞ ratio of amitriptyline/nortriptyline</measure>
    <time_frame>up to 15 days</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>Day 1</time_frame>
    <description>1 hour after BIRT 2584 XX</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of amitriptyline (maximum concentration of amitriptyline in plasma)</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ of nortriptyline (area under the concentration-time curve of nortriptyline in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax of nortriptyline (maximum concentration of nortriptyline in plasma)</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ ratio of amitriptyline/nortriptyline</measure>
    <time_frame>Day 1</time_frame>
    <description>1 hour after BIRT 2584 XX</description>
  </secondary_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 15 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 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant of the analytes in plasma)</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of the analytes in plasma)</measure>
    <time_frame>up to 15 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 15 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 15 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 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose levels of BIRT 2584 XX and BI 610100</measure>
    <time_frame>up to 15 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 57 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of subjects with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 28 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Day 28</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">24</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BIRT 2584 XX + Amitriptyline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BIRT 2584 XX:&#xD;
Days 1 and 2: twice daily (bid) Days 3 to 21: once daily (qd)&#xD;
Amitriptyline:&#xD;
Single dose on day -8, day 1, and day 15</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BIRT 2584 XX</intervention_name>
    <arm_group_label>BIRT 2584 XX + Amitriptyline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Amitriptyline</intervention_name>
    <arm_group_label>BIRT 2584 XX + Amitriptyline</arm_group_label>
    <other_name>Saroten®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy female or male volunteers as determined by the results of screening based upon&#xD;
             a complete medical history, including physical examination, measurement of vital signs&#xD;
             (Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG, and clinical laboratory tests&#xD;
&#xD;
          -  Age ≥ 18 and ≤ 55 years&#xD;
&#xD;
          -  BMI ≥ 18.5 and ≤ 29.9 kg/m2 (body mass index)&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice (GCP) and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any finding of the medical examination (including BP, PR, and ECG) deviating from&#xD;
             normal and of clinical relevance&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic, immunologic,&#xD;
             hematologic, oncologic or hormonal disorders&#xD;
&#xD;
          -  Surgery of gastrointestinal tract (except appendectomy)&#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) which is deemed relevant&#xD;
             to the trial as judged by the investigator&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 h) within 1 month prior to administration&#xD;
             of the study drug or during the trial&#xD;
&#xD;
          -  Use of any drugs which might influence the results of the trial within 10 days prior&#xD;
             to study drug administration or expected during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             administration or expected during the trial&#xD;
&#xD;
          -  Smoker (&gt;10 cigarettes or &gt;3 cigars or &gt;3 pipes/day); inability to abstain from&#xD;
             smoking within 5 days before first drug administration until completion of the trial&#xD;
&#xD;
          -  Alcohol abuse (&gt;60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation or loss &gt;400 mL, within 1 month prior to study drug administration or&#xD;
             expected during the trial&#xD;
&#xD;
          -  Clinically relevant laboratory abnormalities&#xD;
&#xD;
        For male subjects:&#xD;
&#xD;
          -  Male subjects whose sexual partners are currently not using an adequate method of&#xD;
             contraception that would prospectively be maintained during the study, are to be&#xD;
             excluded&#xD;
&#xD;
          -  Male subjects who are not willing to use condoms are to be excluded&#xD;
&#xD;
        For female subjects:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Positive pregnancy test&#xD;
&#xD;
          -  No highly safe method of contraception in women of childbearing potential (in this&#xD;
             context, only sterilization or male partner sterilization is considered a highly safe&#xD;
             method of contraception). Hormonal contraceptives are not considered adequate due to&#xD;
             possible drug interaction with BIRT 2584 XX&#xD;
&#xD;
          -  Lactation period&#xD;
      </textblock>
    </criteria>
    <gender>All</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>Amitriptyline</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/NCT02256878
org study id: 1206.12
nct id: NCT02256878
lead sponsor: 
The objective of the study was evaluate that there is no clinically relevant interaction
      between amitriptyline (or its metabolite nortriptyline) and BIRT 2584 XX (or its metabolite
      BI 610100) when BIRT 2584 XX is administered as a tablet formulation to near steady state in
      an estimated high therapeutic dose. Pharmacokinetics (PK) of amitriptyline and nortriptyline
      were measured before dosing of BIRT 2584 XX, after the first dose of BIRT 2584 XX, and after
      repeated doses of BIRT 2584 XX near steady state
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 15 days
measure: AUC0-∞ ratio of amitriptyline/nortriptyline
time frame: up to 15 days
measure: AUC0-∞ of amitriptyline (area under the concentration-time curve of amitriptyline in plasma over the time interval from 0 extrapolated to infinity)
time frame: Day 1
description: 1 hour after BIRT 2584 XX
measure: Cmax of amitriptyline (maximum concentration of amitriptyline in plasma)
time frame: up to 15 days
measure: AUC0-∞ of nortriptyline (area under the concentration-time curve of nortriptyline in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 15 days
measure: Cmax of nortriptyline (maximum concentration of nortriptyline in plasma)
time frame: up to 15 days
measure: AUC0-∞ ratio of amitriptyline/nortriptyline
time frame: Day 1
description: 1 hour after BIRT 2584 XX
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 15 days
measure: tmax (time from dosing to the maximum concentration of the analytes in plasma)
time frame: up to 15 days
measure: λz (terminal rate constant of the analytes in plasma)
time frame: up to 15 days
measure: t1/2 (terminal half-life of the analytes in plasma)
time frame: up to 15 days
measure: MRTpo (mean residence time of the analytes in the body after po administration)
time frame: up to 15 days
measure: CL/F (apparent clearance of the analytes in the plasma after extravascular administration)
time frame: up to 15 days
measure: Vz/F (apparent volume of distribution during the terminal phase following an extravascular dose)
time frame: up to 15 days
measure: Pre-dose levels of BIRT 2584 XX and BI 610100
time frame: up to 15 days
measure: Number of subjects with adverse events
time frame: up to 57 days
measure: Number of subjects with abnormal changes in laboratory parameters
time frame: up to 28 days
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: Day 28
arm group label: BIRT 2584 XX + Amitriptyline
arm group type: Experimental
description: BIRT 2584 XX:
Days 1 and 2: twice daily (bid) Days 3 to 21: once daily (qd)
Amitriptyline:
Single dose on day -8, day 1, and day 15
intervention type: Drug
intervention name: BIRT 2584 XX
arm group label: BIRT 2584 XX + Amitriptyline
intervention type: Drug
intervention name: Amitriptyline
arm group label: BIRT 2584 XX + Amitriptyline
other name: Saroten®
criteria: 
gender: All
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: Amitriptyline