<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/NCT02259959</url>
  </required_header>
  <id_info>
    <org_study_id>1237.2</org_study_id>
    <nct_id>NCT02259959</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide in Healthy Male Volunteers</brief_title>
  <official_title>Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Multiple Rising Inhalative Doses (2 μg/5 μg, 10 μg/5 μg, and 40 μg/10 μg) of BI 1744 CL in Fixed Dose Combination With Tiotropium Bromide for 14 Days in Healthy Male Volunteers (Double-blind, Randomised, Placebo Controlled [at Each Dose Level] Study)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 1744 CL and&#xD;
      Tiotropium Bromide when given as fixed dose combination&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>April 2007</start_date>
  <primary_completion_date type="Actual">September 2007</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 subjects with clinically relevant findings in physical examination</measure>
    <time_frame>Up to day 32</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant findings in vital signs</measure>
    <time_frame>Up to day 32</time_frame>
    <description>blood pressure, pulse rate</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant findings in 12-lead ECG</measure>
    <time_frame>Up to day 32</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant findings in laboratory tests</measure>
    <time_frame>Up to day 32</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects witch clinically relevant changes in additional safety laboratory test parameters</measure>
    <time_frame>up to 318 hours after start of treatment</time_frame>
    <description>Systemic metabolic parameters: cyclic adenosine mono phosphate (cAMP) and potassium</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically relevant changes in airway resistance (Raw) measured by body plethysmography</measure>
    <time_frame>Pre-dose, up to 408 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>Up to day 32</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Global assessment of tolerability by investigator on a 4-point scale</measure>
    <time_frame>Up to day 32</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum concentration in plasma (Cmax)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to maximum concentration in plasma (tmax)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve in plasma (AUC)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant in plasma (λz)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life in plasma (t½)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time in the body after inhalation (MRTih)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance after extravascular administration (CL/F)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount eliminated in urine from the time point t1 to t2 (Aet1-t2)</measure>
    <time_frame>up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction excreted in urine from time point t1 to t2 (fet1-t2)</measure>
    <time_frame>up to 336 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance from the time point t1 until the time point t2 (CLR,t1-t2)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum measured concentration in plasma at steady state over a uniform dosing interval τ (Cmin,ss)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Predose concentration of the analytes in plasma at steady state immediately before administration of the next dose (Cpre,ss)</measure>
    <time_frame>Pre-dose every 24 hours</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time of last measurable concentration in plasma (tz)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Linearity index (LI)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio based on Cmax (RA,Cmax)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Accumulation ratio based on AUCτ (RA,AUC)</measure>
    <time_frame>up to 504 hours after start of treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">36</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BI 1744 CL in combination with Tiotropium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </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>Single rising doses of BI 1744 CL, solution for oral inhalation</intervention_name>
    <arm_group_label>BI 1744 CL in combination with Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium, fixed dose, solution for oral inhalation</intervention_name>
    <arm_group_label>BI 1744 CL in combination with Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male based upon a complete medical history, including physical examination,&#xD;
             regarding vital signs (BP, PR), 12-lead ECG measurement, and clinical laboratory&#xD;
             tests. There is no finding deviating from normal and of clinical relevance. There is&#xD;
             no evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Age ≥21 and ≤45 years&#xD;
&#xD;
          -  BMI ≥18.5 and &lt;30 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 measurements)&#xD;
             deviating from normal and of clinical relevance&#xD;
&#xD;
          -  Evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Gastrointestinal, hepatic, renal, respiratory, cardiovascular, metabolic,&#xD;
             immunological or hormonal disorders&#xD;
&#xD;
          -  Diseases of the central nervous system (such as epilepsy) or psychiatric disorders or&#xD;
             neurological 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/hypersensitivity (including allergy to the drug or its&#xD;
             excipients) as judged clinically relevant by the investigator&#xD;
&#xD;
          -  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;
          -  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 randomisation&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within 2 months prior to&#xD;
             randomisation&#xD;
&#xD;
          -  Smoker (&gt;10 cigarettes or &gt;3 cigars or &gt;3 pipes/day)&#xD;
&#xD;
          -  Inability to refrain from smoking on trial days as judged by the investigator&#xD;
&#xD;
          -  Alcohol abuse (more than 40 g alcohol a day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL blood within 4 weeks prior to randomisation or during&#xD;
             the trial)&#xD;
&#xD;
          -  Excessive physical activities within 1 week prior to randomisation or during the trial&#xD;
&#xD;
          -  Any laboratory value outside the reference range that is of clinical relevance&#xD;
&#xD;
          -  Inability to comply with dietary regimen of the study centre&#xD;
&#xD;
        The following exclusion criteria are specific for this study due to the known class side&#xD;
        effect profile of ß2-mimetics:&#xD;
&#xD;
          -  Asthma or history of pulmonary hyperreactivity&#xD;
&#xD;
          -  Hyperthyrosis&#xD;
&#xD;
          -  Allergic rhinitis in need of treatment&#xD;
&#xD;
          -  Clinically relevant cardiac arrhythmia&#xD;
&#xD;
          -  Paroxysmal tachycardia (&gt;100 beats per minute)&#xD;
&#xD;
        The following exclusion criteria are specific for this study due to the known class side&#xD;
        effect profile of Tiotropium:&#xD;
&#xD;
          -  Hypersensitivity to tiotropium and/or related drugs of these classes&#xD;
&#xD;
          -  History of narrow-angle glaucoma&#xD;
&#xD;
          -  History of prostatic hyperplasia&#xD;
&#xD;
          -  History of bladder-neck obstruction&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>45 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>Pharmaceutical Solutions</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/NCT02259959
org study id: 1237.2
nct id: NCT02259959
lead sponsor: 
To investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BI 1744 CL and
      Tiotropium Bromide when given as fixed dose combination
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of subjects with clinically relevant findings in physical examination
time frame: Up to day 32
measure: Number of subjects with clinically relevant findings in vital signs
time frame: Up to day 32
description: blood pressure, pulse rate
measure: Number of subjects with clinically relevant findings in 12-lead ECG
time frame: Up to day 32
measure: Number of subjects with clinically relevant findings in laboratory tests
time frame: Up to day 32
measure: Number of subjects witch clinically relevant changes in additional safety laboratory test parameters
time frame: up to 318 hours after start of treatment
description: Systemic metabolic parameters: cyclic adenosine mono phosphate (cAMP) and potassium
measure: Number of subjects with clinically relevant changes in airway resistance (Raw) measured by body plethysmography
time frame: Pre-dose, up to 408 hours after start of treatment
measure: Number of subjects with adverse events
time frame: Up to day 32
measure: Global assessment of tolerability by investigator on a 4-point scale
time frame: Up to day 32
measure: Maximum concentration in plasma (Cmax)
time frame: up to 504 hours after start of treatment
measure: Time from dosing to maximum concentration in plasma (tmax)
time frame: up to 504 hours after start of treatment
measure: Area under the concentration-time curve in plasma (AUC)
time frame: up to 504 hours after start of treatment
measure: Area under the concentration-time curve in plasma over the time interval from 0 extrapolated to infinity (AUC0-∞)
time frame: up to 504 hours after start of treatment
measure: Percentage of AUC 0-∞ that is obtained by extrapolation (%AUCtz-∞)
time frame: up to 504 hours after start of treatment
measure: Terminal rate constant in plasma (λz)
time frame: up to 504 hours after start of treatment
measure: Terminal half-life in plasma (t½)
time frame: up to 504 hours after start of treatment
measure: Mean residence time in the body after inhalation (MRTih)
time frame: up to 504 hours after start of treatment
measure: Apparent clearance after extravascular administration (CL/F)
time frame: up to 504 hours after start of treatment
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (Vz/F)
time frame: up to 504 hours after start of treatment
measure: Amount eliminated in urine from the time point t1 to t2 (Aet1-t2)
time frame: up to 336 hours after start of treatment
measure: Fraction excreted in urine from time point t1 to t2 (fet1-t2)
time frame: up to 336 hours after start of treatment
measure: Renal clearance from the time point t1 until the time point t2 (CLR,t1-t2)
time frame: up to 504 hours after start of treatment
measure: Minimum measured concentration in plasma at steady state over a uniform dosing interval τ (Cmin,ss)
time frame: up to 504 hours after start of treatment
measure: Predose concentration of the analytes in plasma at steady state immediately before administration of the next dose (Cpre,ss)
time frame: Pre-dose every 24 hours
measure: Time of last measurable concentration in plasma (tz)
time frame: up to 504 hours after start of treatment
measure: Linearity index (LI)
time frame: up to 504 hours after start of treatment
measure: Accumulation ratio based on Cmax (RA,Cmax)
time frame: up to 504 hours after start of treatment
measure: Accumulation ratio based on AUCτ (RA,AUC)
time frame: up to 504 hours after start of treatment
arm group label: BI 1744 CL in combination with Tiotropium
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: Single rising doses of BI 1744 CL, solution for oral inhalation
arm group label: BI 1744 CL in combination with Tiotropium
intervention type: Drug
intervention name: Tiotropium, fixed dose, solution for oral inhalation
arm group label: BI 1744 CL in combination with Tiotropium
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: Male
minimum age: 21 Years
maximum age: 45 Years
healthy volunteers: Accepts Healthy Volunteers
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Pharmaceutical Solutions
mesh term: Tiotropium Bromide
mesh term: Olodaterol