<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/NCT02263976</url>
  </required_header>
  <id_info>
    <org_study_id>1205.1</org_study_id>
    <secondary_id>1205.9001</secondary_id>
    <nct_id>NCT02263976</nct_id>
  </id_info>
  <brief_title>Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of BEA 2180 BR in Healthy Male Subjects</brief_title>
  <official_title>Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of Single Rising Inhaled BEA 2180 BR Doses (2.5 μg to 1600 μg Cation Administered With the Respimat®) in Healthy Male Subjects, Alone and Followed by Methacholine Challenge. A Randomised, Double-blind Within Dose Group, Placebo-controlled Study, With a 36 μg Tiotropium Bromide Single Dose Sub-study (Open, Two-fold Crossover).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Main study: To investigate safety, tolerability, pharmacodynamics (PD) and pharmacokinetics&#xD;
      (PK) of BEA 2180 BR Sub-study; To investigate whether treatment with 36 μg tiotropium bromide&#xD;
      is able to protect of methacholine-induced bronchoconstriction compared to baseline&#xD;
      (methacholine challenge at screening).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>August 2003</start_date>
  <primary_completion_date type="Actual">June 2004</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 significant changes in vital signs</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
    <description>blood pressure, pulse rate, respiratory rate, oral body temperature</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically significant changes in laboratory parameters</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline in airway resistance (Raw)</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
    <description>assessed by body plethysmography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes from baseline in specific airway conductance (sGaw)</measure>
    <time_frame>up to 120 hours after drug administration</time_frame>
    <description>assessed by body plethysmography</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of subjects with adverse events</measure>
    <time_frame>up to 14 days after last drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Assessment of tolerability by investigator on a 5-point scale</measure>
    <time_frame>within 14 days after last drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in salivary secretion</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes from baseline in pupil diameter of each eye</measure>
    <time_frame>up to 4 hours after drug administration</time_frame>
    <description>pupillometry</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration of the analyte in plasma (Cmax)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Measured concentration of the analyte in plasma (C) for several time points</measure>
    <time_frame>up to 24 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum concentration of the analyte in plasma (tmax)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of parent drug that is eliminated in urine (Ae)</measure>
    <time_frame>up to 312 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of administered drug excreted unchanged in urine (fe)</measure>
    <time_frame>up to 312 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve of the analyte in plasma (AUC)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte (CLR)</measure>
    <time_frame>up to 312 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal rate constant of the analyte in plasma (λZ)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal half-life of the analyte in plasma (t1/2)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean residence time of the analyte in the body after inhaled administration (MRTinh)</measure>
    <time_frame>up to 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent clearance of the analyte in plasma following extravascular administration (CL/F)</measure>
    <time_frame>up to 240 hours after drug administration</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 240 hours after drug administration</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">101</enrollment>
  <condition>Healthy</condition>
  <arm_group>
    <arm_group_label>BEA 2180 BR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>single rising doses</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-Study</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BEA 2180 BR</intervention_name>
    <arm_group_label>BEA 2180 BR</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>Device</intervention_type>
    <intervention_name>Respimat® A 4</intervention_name>
    <arm_group_label>BEA 2180 BR</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methacholine Chloride</intervention_name>
    <description>methacholine challenge test</description>
    <arm_group_label>BEA 2180 BR</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Sub-Study</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spiriva</intervention_name>
    <arm_group_label>Sub-Study</arm_group_label>
    <other_name>tiotropium bromide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy male volunteers based upon a complete medical history, including the physical&#xD;
             examination, vital signs (BP, PR), 12-lead ECG, clinical laboratory test&#xD;
&#xD;
          -  No finding deviating from normal and of clinical relevance&#xD;
&#xD;
          -  No evidence of a clinically relevant concomitant disease&#xD;
&#xD;
          -  Age ≥ 30 and Age ≤ 55 years&#xD;
&#xD;
          -  Body Mass Index (BMI) ≥ 18.5 and BMI &lt; 30 kg/m2&#xD;
&#xD;
          -  Signed and dated written informed consent prior to admission to the study in&#xD;
             accordance with Good Clinical Practice and the local legislation&#xD;
&#xD;
        Exclusion Criteria:&#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 allergy/hypersensitivity (including drug allergy) which is deemed relevant&#xD;
             to the trial as judged by the investigator (or his deputy)&#xD;
&#xD;
          -  Intake of drugs with a long half-life (&gt; 24 hours) within at least one month or less&#xD;
             than 10 half-lives of the respective drug prior to administration or during the trial&#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 administration&#xD;
             or during the trial&#xD;
&#xD;
          -  Participation in another trial with an investigational drug within two months prior to&#xD;
             administration or during the trial&#xD;
&#xD;
          -  Alcohol abuse (more than 60 g/day)&#xD;
&#xD;
          -  Drug abuse&#xD;
&#xD;
          -  Blood donation (more than 100 mL within four weeks prior to administration or during&#xD;
             the trial)&#xD;
&#xD;
          -  Excessive physical activities (within one week prior to administration or during the&#xD;
             trial)&#xD;
&#xD;
          -  Any laboratory value outside the reference range of clinical relevance&#xD;
&#xD;
        Exclusion criteria specific for this study:&#xD;
&#xD;
          -  Bronchial hyperreactivity as demonstrated by a 45% change of SGaw at or below a&#xD;
             cumulative methacholine concentration of 10 mg/mL = 1%&#xD;
&#xD;
          -  Asthma or bronchial hyperreactivity&#xD;
&#xD;
          -  Allergic rhinitis (hay fever)&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Urinary tract obstruction&#xD;
&#xD;
          -  Epilepsy&#xD;
&#xD;
          -  History of cardiovascular disease&#xD;
&#xD;
          -  History of peptic ulcer disease&#xD;
&#xD;
          -  History of thyroid disease&#xD;
      </textblock>
    </criteria>
    <gender>Male</gender>
    <minimum_age>30 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 13, 2014</study_first_submitted>
  <study_first_submitted_qc>October 13, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 15, 2014</study_first_posted>
  <last_update_submitted>October 13, 2014</last_update_submitted>
  <last_update_submitted_qc>October 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 15, 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>Methacholine Chloride</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/NCT02263976
org study id: 1205.1
secondary id: 1205.9001
nct id: NCT02263976
lead sponsor: 
Main study: To investigate safety, tolerability, pharmacodynamics (PD) and pharmacokinetics
      (PK) of BEA 2180 BR Sub-study; To investigate whether treatment with 36 μg tiotropium bromide
      is able to protect of methacholine-induced bronchoconstriction compared to baseline
      (methacholine challenge at screening).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Number of subjects with clinically significant changes in vital signs
time frame: up to 14 days after last drug administration
description: blood pressure, pulse rate, respiratory rate, oral body temperature
measure: Number of subjects with clinically significant changes in laboratory parameters
time frame: up to 14 days after last drug administration
measure: Changes from baseline in airway resistance (Raw)
time frame: up to 120 hours after drug administration
description: assessed by body plethysmography
measure: Changes from baseline in specific airway conductance (sGaw)
time frame: up to 120 hours after drug administration
description: assessed by body plethysmography
measure: Number of subjects with clinically significant findings in 12-lead ECG (electrocardiogram)
time frame: up to 14 days after last drug administration
measure: Number of subjects with adverse events
time frame: up to 14 days after last drug administration
measure: Assessment of tolerability by investigator on a 5-point scale
time frame: within 14 days after last drug administration
measure: Changes from baseline in salivary secretion
time frame: up to 24 hours after drug administration
measure: Changes from baseline in pupil diameter of each eye
time frame: up to 4 hours after drug administration
description: pupillometry
measure: Maximum measured concentration of the analyte in plasma (Cmax)
time frame: up to 240 hours after drug administration
measure: Measured concentration of the analyte in plasma (C) for several time points
time frame: up to 24 hours after drug administration
measure: Time from dosing to the maximum concentration of the analyte in plasma (tmax)
time frame: up to 240 hours after drug administration
measure: Amount of parent drug that is eliminated in urine (Ae)
time frame: up to 312 hours after drug administration
measure: Fraction of administered drug excreted unchanged in urine (fe)
time frame: up to 312 hours after drug administration
measure: Area under the concentration-time curve of the analyte in plasma (AUC)
time frame: up to 240 hours after drug administration
measure: Renal clearance of the analyte (CLR)
time frame: up to 312 hours after drug administration
measure: Terminal rate constant of the analyte in plasma (λZ)
time frame: up to 240 hours after drug administration
measure: Terminal half-life of the analyte in plasma (t1/2)
time frame: up to 240 hours after drug administration
measure: Mean residence time of the analyte in the body after inhaled administration (MRTinh)
time frame: up to 240 hours after drug administration
measure: Apparent clearance of the analyte in plasma following extravascular administration (CL/F)
time frame: up to 240 hours after drug administration
measure: Apparent volume of distribution during the terminal phase λz following an extravascular dose (VZ/F)
time frame: up to 240 hours after drug administration
arm group label: BEA 2180 BR
arm group type: Experimental
description: single rising doses
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: Sub-Study
arm group type: Experimental
intervention type: Drug
intervention name: BEA 2180 BR
arm group label: BEA 2180 BR
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Device
intervention name: Respimat® A 4
arm group label: BEA 2180 BR
arm group label: Placebo
intervention type: Drug
intervention name: Methacholine Chloride
description: methacholine challenge test
arm group label: BEA 2180 BR
arm group label: Placebo
arm group label: Sub-Study
intervention type: Drug
intervention name: Spiriva
arm group label: Sub-Study
other name: tiotropium bromide
criteria: 
gender: Male
minimum age: 30 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: Bromides
mesh term: Tiotropium Bromide
mesh term: Methacholine Chloride