<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/NCT02236182</url>
  </required_header>
  <id_info>
    <org_study_id>244.2489</org_study_id>
    <nct_id>NCT02236182</nct_id>
  </id_info>
  <brief_title>Study to Assess the Safety of Ipratropium Bromide, in Patients With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>A Double-blind, Placebo Controlled Trial to Assess the Safety of Two-week Administration of 80 mcg q.i.d. and 160 mcg q.i.d. of Ipratropium Bromide, as Delivered by the RESPIMAT® Device, in Patients With Chronic Obstructive Pulmonary Disease</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 assess the safety of two-week administration of 80 and 160 mcg of ipratropium&#xD;
      bromide as delivered by the RESPIMAT® device and as determined by 24 hours ambulatory ECG&#xD;
      monitoring in COPD patients. To assess the overall safety of the two doses of ipratropium&#xD;
      bromide as delivered by the RESPIMAT® device when administered over a two-week period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>July 1998</start_date>
  <primary_completion_date type="Actual">February 1999</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Assessment of clinical significant findings in 24-hour ambulatory ECG monitoring</measure>
    <time_frame>Pre-treatment, on Day 7 and 13</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 15 days after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinical significant findings in ECG</measure>
    <time_frame>Up to 15 days after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinical significant findings in vital signs</measure>
    <time_frame>Up to 15 days after first drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with clinical significant findings in laboratory tests</measure>
    <time_frame>Up to day 15 after drug administration</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with paradoxical bronchospasm</measure>
    <time_frame>Up to 15 days after first drug administration</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>FEV1 (forced expiratory volume in the first second) AUC0-4 (Area under the curve from 0 to 4 hours)</measure>
    <time_frame>Pre-treatment, up to 4 h after drug administration on Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FEV1</measure>
    <time_frame>On Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Onset of therapeutic FEV1 response</measure>
    <time_frame>On Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to peak FEV1 response</measure>
    <time_frame>On Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-6h) (Area under the plasma concentration-time curve from 0 to 6 h)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax (maximum plasma concentration)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin(0h) (minimum plasma concentration before inhalation)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin(6h) (minimum plasma concentration at 6 hours after inhalation)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae(0-2h) (urine excretion between 0 to 2 h)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ae(0-6h) (urine excretion between 0 to 6 h)</measure>
    <time_frame>Day 14</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">57</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Ipratropium Bromide low</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>delivered via RESPIMAT®</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Ipratropium Bromide high</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>delivered via RESPIMAT®</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>delivered via RESPIMAT®</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipratropium Bromide low dose</intervention_name>
    <arm_group_label>Ipratropium Bromide low</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>Ipratropium Bromide high dose</intervention_name>
    <arm_group_label>Ipratropium Bromide high</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All patients must have a diagnosis of COPD and must meet the following spirometric&#xD;
        criteria:&#xD;
&#xD;
          -  Patients must have relatively stable, moderate to severe airway obstruction with an&#xD;
             FEV1 &lt;=65% of predicted normal and FEV1 &lt;=70% of forced vital capacity (FVC).&#xD;
             Predicted normal value will be calculated according to Morris&#xD;
&#xD;
               -  Males: FEV1 = 0.093 (Height in inches)-0.032 (age)-1.343&#xD;
&#xD;
               -  Females: FEV1 = 0.085 (Height. in inches)-0.025(age)-1.692&#xD;
&#xD;
          -  Male or female patients 40 years of age or older&#xD;
&#xD;
          -  Patients must have a smoking history of more than 10 pack-years. A pack-year is&#xD;
             defined as the equivalent of smoking one pack of 20 cigarettes per day for a year&#xD;
&#xD;
          -  Patients must be able to perform pulmonary function tests (PFTs) and maintain records&#xD;
             during the study period as required in the protocol&#xD;
&#xD;
          -  Patients must be able to be trained in the proper use of an inhalation aerosol and the&#xD;
             RESPIMAT™ device&#xD;
&#xD;
          -  Patients must have a baseline electrocardiogram (ECG) with no clinical relevant&#xD;
             arrhythmias or conduction system disease (e.g. right or left bundle branch block,&#xD;
             second degree AV block or higher)&#xD;
&#xD;
          -  Patients must have an oxygen saturation of &gt;=90% for &gt;=92% of the recording time on&#xD;
             overnight oximetry&#xD;
&#xD;
          -  All patients must sign an Informed Consent Form prior to participation in the trial&#xD;
             (i.e., at least 24 hours (h) prior to the screening visit (Visit 1))&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with clinically relevant diseases other than COPD will be excluded. A&#xD;
             clinically relevant disease is defined as a disease which in the opinion of the&#xD;
             investigator may either put the patient at risk because of participation in the study&#xD;
             or a disease with may influence the results of the study or patient's ability to&#xD;
             participate in the study&#xD;
&#xD;
          -  Patients with a recent history (i.e. one year or less) of myocardial infarction&#xD;
&#xD;
          -  Patients with a recent history (i.e. one year or less) of heart failure or patients&#xD;
             with any past history or active cardiac arrhythmia requiring drug therapy&#xD;
&#xD;
          -  Patients who have a pacemaker&#xD;
&#xD;
          -  Patients with clinically relevant abnormal baseline hematology, blood chemistry or&#xD;
             urinalysis. If the abnormality defines a disease listed as an exclusion criterion the&#xD;
             patient is excluded&#xD;
&#xD;
          -  All patients with serum glutamic oxaloacetic transaminase / Aspartate aminotransferase&#xD;
             (SGOT/AST) &gt;80 IU/L, serum glutamic pyruvic transaminase / Alanine transaminase&#xD;
             (SGPT/ALT) &gt;80 IU/L, bilirubin &gt;2.0 mg/dl, or creatinine &gt;2.0 mg/dl will be excluded&#xD;
             regardless of the clinical condition. Repeat laboratory evaluation will be not be&#xD;
             conducted in these subjects&#xD;
&#xD;
          -  Patients who have a blood eosinophil count &gt;=600/mm3. A Repeat eosinophil count will&#xD;
             be not be conducted in these patients&#xD;
&#xD;
          -  Patients with a history of cancer, other than treated basal cell carcinoma, within the&#xD;
             last 5 years&#xD;
&#xD;
          -  Patients with a history of life-threatening pulmonary obstruction, or a history of&#xD;
             cystic fibrosis or bronchiectasis&#xD;
&#xD;
          -  Patients who have undergone thoracotomy with pulmonary resection. Patients with a&#xD;
             history of thoracotomy for other reason should be evaluated per exclusion criterion&#xD;
             No. 1&#xD;
&#xD;
          -  Patients with a history of asthma, allergic rhinitis or atopy&#xD;
&#xD;
          -  Patients with a history of and/or active alcohol or drug abuse&#xD;
&#xD;
          -  Patients with known active tuberculosis&#xD;
&#xD;
          -  Patients with an upper respiratory tract infection or COPD exacerbation in the past 6&#xD;
             weeks prior to the screening visit (Visit 1) or during the baseline period&#xD;
&#xD;
          -  Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction&#xD;
&#xD;
          -  Patients with known narrow-angle glaucoma&#xD;
&#xD;
          -  Patients with current significant psychiatric disorders&#xD;
&#xD;
          -  Patients with regular use of daytime oxygen therapy&#xD;
&#xD;
          -  Patients who are being treated with cromolyn sodium or nedocromil sodium&#xD;
&#xD;
          -  Patients who are being treated with antihistamines&#xD;
&#xD;
          -  Patients using oral corticosteroid medication at unstable doses (i.e. less than six&#xD;
             weeks on a stable dose) or at a dose in excess of the equivalent of 10 mg of&#xD;
             prednisone per day or 20 mg every other day&#xD;
&#xD;
          -  Patients who are being treated with beta-blocker medication&#xD;
&#xD;
          -  Patients who have had changes in their therapeutic plan within the last six weeks&#xD;
             prior to the screening visit (visit 1)&#xD;
&#xD;
          -  Pregnant or nursing women or women of childbearing potential not using a medically&#xD;
             approved means of contraception (e.g., oral contraceptive, intrauterine devices,&#xD;
             diaphragm or Norplant®)&#xD;
&#xD;
          -  Patients with known hypersensitivity to ant cholinergic drugs or any other components&#xD;
             of the ATROVENT® RESPIMAT™ solution including bacteriostatic agent benzalkonium&#xD;
             chlorid (BAC) and edetic acid (EDTA)&#xD;
&#xD;
          -  Patients who have taken an investigational drug within 1 month or 6 half-lives&#xD;
             (whichever is longer) prior to the screening visit (visit1)&#xD;
&#xD;
          -  Previous participation in this study&#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 9, 2014</study_first_submitted>
  <study_first_submitted_qc>September 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 10, 2014</study_first_posted>
  <last_update_submitted>September 11, 2014</last_update_submitted>
  <last_update_submitted_qc>September 11, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 12, 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>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <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>Bromides</mesh_term>
    <mesh_term>Ipratropium</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/NCT02236182
org study id: 244.2489
nct id: NCT02236182
lead sponsor: 
Study to assess the safety of two-week administration of 80 and 160 mcg of ipratropium
      bromide as delivered by the RESPIMAT® device and as determined by 24 hours ambulatory ECG
      monitoring in COPD patients. To assess the overall safety of the two doses of ipratropium
      bromide as delivered by the RESPIMAT® device when administered over a two-week period.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Assessment of clinical significant findings in 24-hour ambulatory ECG monitoring
time frame: Pre-treatment, on Day 7 and 13
measure: Number of patients with adverse events
time frame: Up to 15 days after first drug administration
measure: Number of patients with clinical significant findings in ECG
time frame: Up to 15 days after first drug administration
measure: Number of patients with clinical significant findings in vital signs
time frame: Up to 15 days after first drug administration
measure: Number of patients with clinical significant findings in laboratory tests
time frame: Up to day 15 after drug administration
measure: Number of patients with paradoxical bronchospasm
time frame: Up to 15 days after first drug administration
measure: FEV1 (forced expiratory volume in the first second) AUC0-4 (Area under the curve from 0 to 4 hours)
time frame: Pre-treatment, up to 4 h after drug administration on Day 1 and 14
measure: Peak FEV1
time frame: On Day 1 and 14
measure: Onset of therapeutic FEV1 response
time frame: On Day 1 and 14
measure: Time to peak FEV1 response
time frame: On Day 1 and 14
measure: AUC(0-6h) (Area under the plasma concentration-time curve from 0 to 6 h)
time frame: Day 14
measure: Cmax (maximum plasma concentration)
time frame: Day 14
measure: Cmin(0h) (minimum plasma concentration before inhalation)
time frame: Day 14
measure: Cmin(6h) (minimum plasma concentration at 6 hours after inhalation)
time frame: Day 14
measure: Ae(0-2h) (urine excretion between 0 to 2 h)
time frame: Day 14
measure: Ae(0-6h) (urine excretion between 0 to 6 h)
time frame: Day 14
arm group label: Ipratropium Bromide low
arm group type: Experimental
description: delivered via RESPIMAT®
arm group label: Ipratropium Bromide high
arm group type: Experimental
description: delivered via RESPIMAT®
arm group label: Placebo
arm group type: Placebo Comparator
description: delivered via RESPIMAT®
intervention type: Drug
intervention name: Ipratropium Bromide low dose
arm group label: Ipratropium Bromide low
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
intervention type: Drug
intervention name: Ipratropium Bromide high dose
arm group label: Ipratropium Bromide high
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: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Bromides
mesh term: Ipratropium