<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/NCT02242279</url>
  </required_header>
  <id_info>
    <org_study_id>1205.3</org_study_id>
    <nct_id>NCT02242279</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Efficacy and Safety of Inhaled BEA 2180 BR in COPD Patients</brief_title>
  <official_title>Randomised, Double-Blind, Placebo-Controlled, 4-Way Cross-Over Study to Assess the Efficacy and Safety of a Single Dose of Orally Inhaled BEA 2180 BR (Doses 80, 200 and 800 μg) in COPD Patients Followed by an Open-Label, Active-Control (Tiotropium 72 μg)</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 the dose-dependent bronchodilator effect and the safety of single&#xD;
      inhalation doses of BEA 2180 inhaled via Respimat® compared to placebo in patients with&#xD;
      stable Chronic Obstructive Pulmonary Disease (COPD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2004</start_date>
  <primary_completion_date type="Actual">December 2004</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Mean Forced Expiratory Volume in 1st second (FEV1)</measure>
    <time_frame>23 and 24 hours after single inhalation</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in FEV1 Area under the concentration-time curve over the respective time interval (AUCtime-interval)</measure>
    <time_frame>predose, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 23, 24, 26 and 28 hours after inhalation of each single dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FEV1</measure>
    <time_frame>within 3 hours after inhalation of each single dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to peak bronchodilatory response</measure>
    <time_frame>within 3 hours after inhalation of each single dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Forced Vital Capacity (FVC) AUCtime-interval</measure>
    <time_frame>predose, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 23, 24, 26 and 28 hours after inhalation of each single dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in individual FEV1 measurements</measure>
    <time_frame>up to 71 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in individual FVC measurements</measure>
    <time_frame>up to 71 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 85 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration-time curve over the respective time interval (AUCtime-interval)</measure>
    <time_frame>predose, 5 min, 30min, 2 h, 8 h , 24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pre-dose plasma concentration immediately before the inhalation of each single dose (Cpre)</measure>
    <time_frame>predose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum measured plasma concentration following the inhalation of each single dose (Cmax)</measure>
    <time_frame>predose, 5 min, 30min, 2 h, 8 h , 24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time from dosing to the maximum plasma concentration the inhalation of each single dose of randomised treatment (tmax)</measure>
    <time_frame>predose, 5 min, 30min, 2 h, 8 h , 24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of unchanged drug excreted over the respective time intervals (Aetime-interval)</measure>
    <time_frame>predose, 0-4 h, 4-24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2)</measure>
    <time_frame>predose, 0-4 h, 4-24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fraction of analyte eliminated in urine from different time intervals (fetime-interval)</measure>
    <time_frame>predose, 0-4 h, 4-24 h</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FVC</measure>
    <time_frame>within 3 hours after inhalation of each single dose</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">37</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>BEA 2180 - low dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BEA 2180 - medium dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BEA 2180 - high dose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium</arm_group_label>
    <arm_group_type>Active Comparator</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>BEA 2180 BR</intervention_name>
    <arm_group_label>BEA 2180 - high dose</arm_group_label>
    <arm_group_label>BEA 2180 - low dose</arm_group_label>
    <arm_group_label>BEA 2180 - medium dose</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <arm_group_label>Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>BEA 2180 - medium dose</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All patients have to sign and date an informed consent consistent with International&#xD;
             committee on harmonisation (ICH) - Good Clinical Practice (GCP) guidelines prior to&#xD;
             participation in the trial, which included medication washout and restrictions&#xD;
&#xD;
          2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must&#xD;
             meet the following spirometric criteria:&#xD;
&#xD;
             Patients must have relatively stable, moderate to severe airway obstruction with an&#xD;
             FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC (Visits 1 and 2)&#xD;
&#xD;
          3. All patients must have an increase in FEV1 of at least 12% from baseline 45 min after&#xD;
             inhalation of 80 μg of ipratropium inhaled via Hydro Fluoro Alkane (HFA) - Metered&#xD;
             Dose Inhaler (MDI)&#xD;
&#xD;
          4. Male or female patients 40 years of age or older. Female patients of child bearing&#xD;
             potential could not participate in this study&#xD;
&#xD;
          5. Patients must be current or ex-smokers with a smoking history of more than 10&#xD;
             pack/years&#xD;
&#xD;
               -  (Patients who have never smoked cigarettes must be excluded)&#xD;
&#xD;
          6. Patients must be able to perform technically acceptable pulmonary function tests and&#xD;
             inhale medication in a competent manner from the Respimat® device and the HandiHaler®&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with significant diseases other than Chronic Obstructive Pulmonary Disease&#xD;
             (COPD) must be excluded. A significant disease is defined as a disease which in the&#xD;
             opinion of the investigator may either put the patient at risk because of&#xD;
             participation in the study or a disease which may influence the results of the study&#xD;
             or the patient's ability to participate in the study&#xD;
&#xD;
          2. Patients with clinically relevant abnormal baseline hematology, blood chemistry, or&#xD;
             urinalysis, if the abnormality defines a significant disease&#xD;
&#xD;
          3. Patients with significant prostatic hyperplasia&#xD;
&#xD;
          4. Patients with a recent history (i.e. one year or less) of myocardial infarction&#xD;
&#xD;
          5. Patients with any unstable or life-threatening cardiac arrhythmia or patients who have&#xD;
             been hospitalized for such an event within the past year&#xD;
&#xD;
          6. Patients with a history (less than 3 years) of cardiac failure, cor pulmonale or&#xD;
             cardiac arrhythmia requiring drug therapy&#xD;
&#xD;
          7. Patients with a malignancy for which the patient has undergone resection, radiation&#xD;
             therapy or chemotherapy within the last five years. Patients with treated basal cell&#xD;
             carcinoma are allowed&#xD;
&#xD;
          8. Patients with known narrow-angle glaucoma&#xD;
&#xD;
          9. Patients with a history of asthma, allergic rhinitis or who have a total blood&#xD;
             eosinophil count ≥ 600/mm3. A repeat eosinophil count was not conducted in these&#xD;
             patients&#xD;
&#xD;
         10. Patients with a history of life-threatening pulmonary obstruction, or a history of&#xD;
             cystic fibrosis or clinically evident bronchiectasis&#xD;
&#xD;
         11. Patients with known active tuberculosis&#xD;
&#xD;
         12. Patients with a history of and/or active significant alcohol or drug abuse&#xD;
&#xD;
         13. Patients who have undergone thoracotomy with pulmonary resection. Patients with a&#xD;
             history of thoracotomy for other reasons must be excluded&#xD;
&#xD;
         14. Patients who have completed a pulmonary rehabilitation program in the six weeks prior&#xD;
             to the Screening Visit (Visit 1)&#xD;
&#xD;
         15. Patients who regularly used daytime oxygen therapy&#xD;
&#xD;
         16. Patients who have taken an investigational drug within one month or six half lives&#xD;
             (whichever is greater) prior to Screening Visit (Visit 1)&#xD;
&#xD;
         17. Patients who are being treated with oral beta-adrenergic&#xD;
&#xD;
         18. Patients who are being treated with beta-blockers&#xD;
&#xD;
         19. Patients who are being treated with cromolyn sodium or nedocromil sodium&#xD;
&#xD;
         20. Patients who are being treated with antihistamines (H1 receptor antagonists),&#xD;
             antileukotrienes or leukotriene receptor antagonists for asthma or excluded allergic&#xD;
             conditions&#xD;
&#xD;
         21. Patients using oral corticosteroid medication at unstable doses (i.e., less than six&#xD;
             weeks on a stable dose) or at doses in excess of the equivalent of 10 mg of prednisone&#xD;
             per day or 20 mg every other day&#xD;
&#xD;
         22. Patients with known hypersensitivity to anticholinergic drugs, beta-adrenergic,&#xD;
             lactose or any other components of the medication delivery systems&#xD;
&#xD;
         23. Pregnant or nursing women or women of childbearing potential. Female patients have to&#xD;
             be either:&#xD;
&#xD;
               -  Surgically sterilized by hysterectomy or bilateral tubal ligation or&#xD;
&#xD;
               -  Post-menopausal for at least two years&#xD;
&#xD;
         24. Patients with previous participation (receipt of randomized treatment) in this study&#xD;
&#xD;
         25. Patients who are participating in another study&#xD;
&#xD;
         26. The randomization of patients with any respiratory infection or COPD exacerbation in&#xD;
             the six weeks prior to the Screening Visit (Visit 1) or during the baseline period&#xD;
             must be postponed. Patients could be randomized six weeks following recovery from the&#xD;
             infection or exacerbation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <link>
    <url>http://trials.boehringer-ingelheim.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2014</verification_date>
  <study_first_submitted>September 16, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <last_update_submitted>September 16, 2014</last_update_submitted>
  <last_update_submitted_qc>September 16, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 17, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tiotropium Bromide</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/NCT02242279
org study id: 1205.3
nct id: NCT02242279
lead sponsor: 
Study to investigate the dose-dependent bronchodilator effect and the safety of single
      inhalation doses of BEA 2180 inhaled via Respimat® compared to placebo in patients with
      stable Chronic Obstructive Pulmonary Disease (COPD)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double
measure: Change in Mean Forced Expiratory Volume in 1st second (FEV1)
time frame: 23 and 24 hours after single inhalation
measure: Change in FEV1 Area under the concentration-time curve over the respective time interval (AUCtime-interval)
time frame: predose, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 23, 24, 26 and 28 hours after inhalation of each single dose
measure: Peak FEV1
time frame: within 3 hours after inhalation of each single dose
measure: Time to peak bronchodilatory response
time frame: within 3 hours after inhalation of each single dose
measure: Change in Forced Vital Capacity (FVC) AUCtime-interval
time frame: predose, 30, 60 minutes, 2, 3, 4, 6, 8, 10, 12, 23, 24, 26 and 28 hours after inhalation of each single dose
measure: Change in individual FEV1 measurements
time frame: up to 71 days
measure: Change in individual FVC measurements
time frame: up to 71 days
measure: Number of patients with adverse events
time frame: up to 85 days
measure: Area under the plasma concentration-time curve over the respective time interval (AUCtime-interval)
time frame: predose, 5 min, 30min, 2 h, 8 h , 24 h
measure: Pre-dose plasma concentration immediately before the inhalation of each single dose (Cpre)
time frame: predose
measure: Maximum measured plasma concentration following the inhalation of each single dose (Cmax)
time frame: predose, 5 min, 30min, 2 h, 8 h , 24 h
measure: Time from dosing to the maximum plasma concentration the inhalation of each single dose of randomised treatment (tmax)
time frame: predose, 5 min, 30min, 2 h, 8 h , 24 h
measure: Amount of unchanged drug excreted over the respective time intervals (Aetime-interval)
time frame: predose, 0-4 h, 4-24 h
measure: Renal clearance of the analyte from the time point t1 until the time point t2 (CLR,t1-t2)
time frame: predose, 0-4 h, 4-24 h
measure: Fraction of analyte eliminated in urine from different time intervals (fetime-interval)
time frame: predose, 0-4 h, 4-24 h
measure: Peak FVC
time frame: within 3 hours after inhalation of each single dose
arm group label: BEA 2180 - low dose
arm group type: Experimental
arm group label: BEA 2180 - medium dose
arm group type: Experimental
arm group label: BEA 2180 - high dose
arm group type: Experimental
arm group label: Tiotropium
arm group type: Active Comparator
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BEA 2180 BR
arm group label: BEA 2180 - high dose
arm group label: BEA 2180 - low dose
arm group label: BEA 2180 - medium dose
intervention type: Drug
intervention name: Tiotropium
arm group label: Tiotropium
intervention type: Drug
intervention name: Placebo
arm group label: BEA 2180 - medium dose
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Tiotropium Bromide