<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/NCT02259946</url>
  </required_header>
  <id_info>
    <org_study_id>1237.1</org_study_id>
    <nct_id>NCT02259946</nct_id>
  </id_info>
  <brief_title>Study to Investigate Safety and Tolerability of BI 1744 CL in Free Dose Combination With Tiotropium Bromide Both Administered by Respimat® in Healthy Male Volunteers</brief_title>
  <official_title>A Randomised, Double-blind, Placebo-controlled (Within Dose Groups) Study to Assess Safety, Tolerability and Pharmacokinetics of Single Rising Inhaled Doses (2.5 μg, 5 μg, 10 μg, 20 μg and 40 μg) of BI 1744 CL (Administered With the Respimat®) in Free Dose Combination With Tiotropium Bromide 5 μg ( for Doses up to and Including 20 μg BI 1744 CL), 10 μg (for Doses of 20 μg and 40 μg BI 1744 CL) (Administered With the Respimat®) 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>
      Study to investigate safety and tolerability of single, inhaled doses (2.5 μg, 5 μg, 10 μg,&#xD;
      20 μg and 40 μg) of BI 1744 CL in free dose combination with tiotropium bromide 5 μg (for&#xD;
      doses up to and including 20 μg BI 1744 CL) and 10 μg (for doses of 20 μg and 40 μg BI 1744&#xD;
      CL), both administered by Respimat® in healthy male volunteers. Also, to investigate the&#xD;
      pharmacokinetics of BI 1744 BS and tiotropium bromide in such combinations, to explore their&#xD;
      dose proportionality, and to explore the pharmacodynamic effects of the treatments on&#xD;
      selected metabolic and respiratory parameters&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2006</start_date>
  <primary_completion_date type="Actual">July 2006</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with abnormal findings in physical examination</measure>
    <time_frame>up to 12 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with abnormal changes in laboratory parameters</measure>
    <time_frame>up to 12 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes in vital signs</measure>
    <time_frame>up to 12 days after drug administration</time_frame>
    <description>blood pressure (BP), pulse rate (PR), respiratory rate (RR)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with adverse events</measure>
    <time_frame>up to 12 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants with clinically significant changes in 12-lead ECG</measure>
    <time_frame>up to 12 days after drug administration</time_frame>
    <description>cardiac axis, heart rate, PQ interval, QRS interval, uncorrected QT interval, HR-corrected QT-interval according to Bazett and Fridericia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of abnormal findings on oropharyngeal inspection</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of abnormal findings on pulmonary auscultation</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>12 days after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Airway resistance (Raw)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
    <description>measured by whole-body plethysmography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in specific conductance (sGaw)</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
    <description>measured by whole-body plethysmography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Cyclic aminomonophosphate (cAMP)</measure>
    <time_frame>up to 6 hours after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in potassium</measure>
    <time_frame>up to 6 hours after drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum measured concentration of BI 1744 BS and tiotropium in plasma)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>tmax (time from dosing to maximum measured concentration)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-∞ (area under the concentration-time curve of BI 1744 BS and tiotropium in plasma over the time interval from 0 extrapolated to infinity)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-tz (area under the concentration-time curve of the analyte salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>%AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>λz (terminal rate constant in plasma)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 (terminal half-life of BI 1744 BS and tiotropium in plasma)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MRTih (mean residence time of BI 1744 BS and tiotropium in the body after inhalation)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CL/F (apparent clearance of BI 1744 BS and tiotropium in plasma after extravascular administration)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Aet1-t2 (amount of BI 1744 BS and tiotropium eliminated in urine from the time point t1 to time point t2)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fet1-t2 (fraction of BI 1744 BS and tiotropium eliminated in urine from time point t1 to time point t2)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CLR,t1-t2 (renal clearance of BI 1744 BS and tiotropium from the time point t1 until the time point t2)</measure>
    <time_frame>up to 96 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">48</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 1744 CL - single rising dose + Tiotropium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single rising dose of BI 1744 CL (conjointly with Tiotropium bromide)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1744 CL</intervention_name>
    <arm_group_label>BI 1744 CL - single rising dose + Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium bromide</intervention_name>
    <arm_group_label>BI 1744 CL - single rising dose + Tiotropium</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Healthy male based upon a complete medical history, including the physical&#xD;
             examination, regarding vital signs (Blood Pressure (BP), Pulse Rate (PR)), 12-lead ECG&#xD;
             measurement, and clinical laboratory tests. Absence of any clinically relevant&#xD;
             abnormality. Absence of any clinically relevant concomitant disease&#xD;
&#xD;
          2. Age ≥21 and ≤50 years&#xD;
&#xD;
          3. BMI ≥18.5 and &lt;30 kg/m2 (Body Mass Index)&#xD;
&#xD;
          4. 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;
          1. Any finding of the medical examination (including BP, PR, and ECG measurements)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          2. Evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          3. Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          4. Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological disorders&#xD;
&#xD;
          5. History of relevant orthostatic hypotension, fainting spells or blackouts&#xD;
&#xD;
          6. Chronic or relevant acute infections&#xD;
&#xD;
          7. History of relevant allergy/hypersensitivity (including allergy to the drug or its&#xD;
             excipients) as judged clinically relevant by the investigator&#xD;
&#xD;
          8. Intake of drugs with a long half-life (&gt;24 hours) within at least 1 month or less than&#xD;
             10 half-lives of the respective drug prior to randomization&#xD;
&#xD;
          9. Use of drugs which might reasonably influence the results of the trial based on the&#xD;
             knowledge at the time of protocol preparation within 10 days prior to enrolment in the&#xD;
             study or during the study&#xD;
&#xD;
         10. Participation in another trial with an investigational drug within 2 months prior to&#xD;
             randomization&#xD;
&#xD;
         11. Smoker (&gt;10 cigarettes or &gt;3 cigars or &gt;3 pipes/day)&#xD;
&#xD;
         12. Inability to refrain from smoking on trial days as judged by the investigator&#xD;
&#xD;
         13. Alcohol abuse (regularly more than 40 g alcohol per day for men)&#xD;
&#xD;
         14. Drug abuse&#xD;
&#xD;
         15. Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during&#xD;
             the trial)&#xD;
&#xD;
         16. Excessive physical activities within 1 week prior to randomization or during the trial&#xD;
&#xD;
         17. Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
         18. Inability to comply with dietary regimen of the study centre&#xD;
&#xD;
             Additionally, following exclusion criteria that are of particular relevance with&#xD;
             regard to the known properties of BI 1744 CL as a ß-adrenoceptor agonist must be&#xD;
             adhered to:&#xD;
&#xD;
         19. Asthma or history of pulmonary hyperreactivity&#xD;
&#xD;
         20. Hyperthyrosis&#xD;
&#xD;
         21. Allergic rhinitis in need of treatment&#xD;
&#xD;
         22. Clinically relevant cardiac arrhythmia&#xD;
&#xD;
         23. Paroxysmal tachycardia&#xD;
&#xD;
             Furthermore, the following exclusion criteria that are of particular relevance with&#xD;
             regard to the known properties of tiotropium as an antimuscarinic anticholinergic&#xD;
             agent must be adhered to:&#xD;
&#xD;
         24. Hypersensitivity to tiotropium and/or related drugs of these classes&#xD;
&#xD;
         25. History of narrow-angle glaucoma&#xD;
&#xD;
         26. History of prostatic hyperplasia&#xD;
&#xD;
         27. History of bladder-neck obstruction&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>50 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 7, 2014</study_first_submitted>
  <study_first_submitted_qc>October 7, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 9, 2014</study_first_posted>
  <last_update_submitted>October 7, 2014</last_update_submitted>
  <last_update_submitted_qc>October 7, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 9, 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>Bromides</mesh_term>
    <mesh_term>Tiotropium Bromide</mesh_term>
    <mesh_term>Olodaterol</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/NCT02259946
org study id: 1237.1
nct id: NCT02259946
lead sponsor: 
Study to investigate safety and tolerability of single, inhaled doses (2.5 μg, 5 μg, 10 μg,
      20 μg and 40 μg) of BI 1744 CL in free dose combination with tiotropium bromide 5 μg (for
      doses up to and including 20 μg BI 1744 CL) and 10 μg (for doses of 20 μg and 40 μg BI 1744
      CL), both administered by Respimat® in healthy male volunteers. Also, to investigate the
      pharmacokinetics of BI 1744 BS and tiotropium bromide in such combinations, to explore their
      dose proportionality, and to explore the pharmacodynamic effects of the treatments on
      selected metabolic and respiratory parameters
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of participants with abnormal findings in physical examination
time frame: up to 12 days after drug administration
measure: Number of participants with abnormal changes in laboratory parameters
time frame: up to 12 days after drug administration
measure: Number of participants with clinically significant changes in vital signs
time frame: up to 12 days after drug administration
description: blood pressure (BP), pulse rate (PR), respiratory rate (RR)
measure: Number of participants with adverse events
time frame: up to 12 days after drug administration
measure: Number of participants with clinically significant changes in 12-lead ECG
time frame: up to 12 days after drug administration
description: cardiac axis, heart rate, PQ interval, QRS interval, uncorrected QT interval, HR-corrected QT-interval according to Bazett and Fridericia
measure: Number of abnormal findings on oropharyngeal inspection
time frame: up to 24 hours after drug administration
measure: Number of abnormal findings on pulmonary auscultation
time frame: up to 24 hours after drug administration
measure: Assessment of tolerability by investigator on a 4-point scale
time frame: 12 days after drug administration
measure: Change in Airway resistance (Raw)
time frame: up to 24 hours after drug administration
description: measured by whole-body plethysmography
measure: Change in specific conductance (sGaw)
time frame: up to 24 hours after drug administration
description: measured by whole-body plethysmography
measure: Change in Cyclic aminomonophosphate (cAMP)
time frame: up to 6 hours after drug administration
measure: Change in potassium
time frame: up to 6 hours after drug administration
measure: Cmax (maximum measured concentration of BI 1744 BS and tiotropium in plasma)
time frame: up to 96 hours after drug administration
measure: tmax (time from dosing to maximum measured concentration)
time frame: up to 96 hours after drug administration
measure: AUC0-∞ (area under the concentration-time curve of BI 1744 BS and tiotropium in plasma over the time interval from 0 extrapolated to infinity)
time frame: up to 96 hours after drug administration
measure: AUC0-tz (area under the concentration-time curve of the analyte salmeterol in plasma over the time interval from 0 to the time of the last quantifiable data point)
time frame: up to 96 hours after drug administration
measure: %AUCtz-∞ (percentage of the extrapolated part of the total AUC0-∞)
time frame: up to 96 hours after drug administration
measure: λz (terminal rate constant in plasma)
time frame: up to 96 hours after drug administration
measure: t1/2 (terminal half-life of BI 1744 BS and tiotropium in plasma)
time frame: up to 96 hours after drug administration
measure: MRTih (mean residence time of BI 1744 BS and tiotropium in the body after inhalation)
time frame: up to 96 hours after drug administration
measure: CL/F (apparent clearance of BI 1744 BS and tiotropium in plasma after extravascular administration)
time frame: up to 96 hours after drug administration
measure: Vz/F (apparent volume of distribution during the terminal phase λz following an extravascular dose)
time frame: up to 96 hours after drug administration
measure: Aet1-t2 (amount of BI 1744 BS and tiotropium eliminated in urine from the time point t1 to time point t2)
time frame: up to 96 hours after drug administration
measure: fet1-t2 (fraction of BI 1744 BS and tiotropium eliminated in urine from time point t1 to time point t2)
time frame: up to 96 hours after drug administration
measure: CLR,t1-t2 (renal clearance of BI 1744 BS and tiotropium from the time point t1 until the time point t2)
time frame: up to 96 hours after drug administration
arm group label: BI 1744 CL - single rising dose + Tiotropium
arm group type: Experimental
description: Single rising dose of BI 1744 CL (conjointly with Tiotropium bromide)
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BI 1744 CL
arm group label: BI 1744 CL - single rising dose + Tiotropium
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Tiotropium bromide
arm group label: BI 1744 CL - single rising dose + Tiotropium
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Bromides
mesh term: Tiotropium Bromide
mesh term: Olodaterol