<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/NCT02249338</url>
  </required_header>
  <id_info>
    <org_study_id>543.10</org_study_id>
    <nct_id>NCT02249338</nct_id>
  </id_info>
  <brief_title>Effect of BIIL 284 BS on Patients With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>Effect of 14-Day Treatment With BIIL 284 BS on Patients With COPD (Double-Blind, Placebo-Controlled, Randomised, Parallel Group 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>
      Study to investigate the effect of 14-day treatment with BIIL 284 BS on sputum neutrophils&#xD;
      and specific inflammatory markers in patients with clinically well-defined moderate chronic&#xD;
      obstructive pulmonary disease (COPD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 1999</start_date>
  <primary_completion_date type="Actual">April 2000</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>Percentage of neutrophils in the induced sputum differential cell count</measure>
    <time_frame>Baseline, day 14</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of neutrophils in the spontaneous sputum differential cell count</measure>
    <time_frame>Baseline, day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of neutrophils in the induced sputum differential cell count</measure>
    <time_frame>Baseline, day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of neutrophils in the spontaneous sputum differential cell count</measure>
    <time_frame>Baseline, day 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differential cell count in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
    <description>macrophages, lymphocytes, eosinophils, basophils and epithelial cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Differential cell count in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
    <description>macrophages, lymphocytes, eosinophils, basophils and epithelial cells</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Wet weight of spontaneous sputum</measure>
    <time_frame>Day -6, 0, 6, 13 and 27</time_frame>
    <description>collected over a 24 hours period the day before each clinic visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of myeloperoxidase (MPO) in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of myeloperoxidase (MPO) in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of neutrophil elastase (NE) in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of neutrophil elastase (NE) in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of interleukin-8 (IL-8) in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of interleukin-8 (IL-8) in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of leukotriene B4 (LTB4) in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of leukotriene B4 (LTB4) in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of albumin in induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of albumin in spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum bacterial load of induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum bacterial load of spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum chemotactic activity of induced sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Sputum chemotactic activity of spontaneous sputum</measure>
    <time_frame>Baseline, day 14 and 28</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of blood neutrophil Mac-1 expression</measure>
    <time_frame>Day 1 and 14</time_frame>
    <description>both unstimulated and LTB4-stimulated</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inhibition of blood neutrophil chemotaxis response to LTB4</measure>
    <time_frame>Day 1 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced expiratory volume in one second (FEV1)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced vital capacity (FVC)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced expiratory flow (FEF25-75%)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak expiratory flow rate (PEFR)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Inspiratory capacity (IC)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Slow vital capacity (SVC)</measure>
    <time_frame>Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in COPD symptom score</measure>
    <time_frame>Baseline, Day 1, 7 and 14</time_frame>
    <description>dyspnoea, fatigue, orthopnea, paroxysmal nocturnal dyspnoea and cough</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Physician's global evaluation of symptoms assessed on a 4-point scale</measure>
    <time_frame>Baseline, Day 14</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>up to 6 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentrations of the analytes</measure>
    <time_frame>30 min before, 90 and 240 min after drug administration on day 1 and 14</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">53</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>BIIL 284 BS</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>BIIL 284 BS</intervention_name>
    <arm_group_label>BIIL 284 BS</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;
          -  A diagnosis of COPD as defined by the American Thoracic Society criteria. Patients&#xD;
             must have relatively stable, moderate to severe airway obstruction with an FEV1 ≤ 70 %&#xD;
             of predicted value and FEV1/FVC ≤ 70 % at Screening Visit 1&#xD;
&#xD;
          -  Ability to produce an adequate induced sputum sample ad defined by: volume &gt; 1 ml:&#xD;
             squamous cells less than 80% and the ability to tolerate the procedure for at least&#xD;
             four minutes with no bronchoconstriction ( a fall in FEV1 ≥ 20%)&#xD;
&#xD;
          -  Greater than 50% of neutrophils in induced-sputum cells at visit 1. This requirement&#xD;
             refers to the neutrophils percentage excluding squamous cells&#xD;
&#xD;
          -  Males or females aged 40 to 80 years inclusive.&#xD;
&#xD;
          -  Female patients of childbearing potential cannot participate in this study. Female&#xD;
             patients participating in this study must meet at least one of the following criteria:&#xD;
&#xD;
               -  surgically sterilized by hysterectomy or bilateral tubal ligation&#xD;
&#xD;
               -  post-menopausal for at least two years&#xD;
&#xD;
          -  A smoking history of more than ten pack years. A pack-year is defined as the&#xD;
             equivalent of smoking one pack of 20 cigarettes per day for a year&#xD;
&#xD;
          -  Patients must be able to perform pulmonary function tests and maintain records during&#xD;
             the study period as required in the protocol&#xD;
&#xD;
          -  All patients must sign an Informed Consent Form prior tho participation in the trial,&#xD;
             i.e., prior to pre-study washout of their usual pulmonary medications&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Culture-documented and/or radiographic evidence and/or antibiotic treatment of an&#xD;
             upper or lower respiratory tract infection within the previous 4 weeks or during the&#xD;
             baseline period of this study&#xD;
&#xD;
          -  Significant diseases other than COPD will be exclude. A significant disease is defined&#xD;
             as a disease which in the opinion of the investigator may either put the patient at&#xD;
             risk because of participation in the study or a disease which may influence the&#xD;
             results of the study or the patient's ability to participate in the study. Patients&#xD;
             with inflammatory diseases e.g. rheumatoid arthritis, and those with autoimmune&#xD;
             diseases will be excluded&#xD;
&#xD;
          -  Clinically significant abnormal baseline haematology, liver function, blood chemistry&#xD;
             or urinalysis, if the abnormality defines a disease listed as an exclusion criterion&#xD;
             will be excluded. Laboratory parameters listed in the protocol must be within normal&#xD;
             range, or if not, be documented by the investigator as not clinically relevant. The&#xD;
             following tests may be outside the normal range to the extent indicated:&#xD;
&#xD;
               -  Aspartate transaminase, Alanine transaminase, Total Bilirubin, Alkaline&#xD;
                  Phosphatase: 10% &gt; upper limit of normal (ULN)&#xD;
&#xD;
               -  White blood cell count &lt; 3.80 x 10**9/L, Neutrophils &lt; 2.00 x 10**9/L, Platelets&#xD;
                  &lt; 100 x 10**9/L, Hemoglobin &lt; 12 x g/dL&#xD;
&#xD;
               -  Urea Nitrogen, Creatinine: 10% &gt; ULN&#xD;
&#xD;
          -  A recent history (i.e. within six months) of myocardial infarction&#xD;
&#xD;
          -  A recent history (i.e. within three months) of refractory heart failure or unstable&#xD;
             arrhythmias requiring treatment&#xD;
&#xD;
          -  Patients with known active tuberculosis&#xD;
&#xD;
          -  A history of cancer within the last five years. Patients with treated basal cell&#xD;
             carcinoma or cutaneous squamous cell carcinoma are allowed&#xD;
&#xD;
          -  A history of life-threatening pulmonary obstruction, or a history of cystic fibrosis&#xD;
             or bronchiectasis&#xD;
&#xD;
          -  Previous thoracotomy with pulmonary resection. Patients with a history of a&#xD;
             thoracotomy without pulmonary resection should be evaluated as per exclusion criterion&#xD;
             no. 2&#xD;
&#xD;
          -  The use of oral corticosteroids within 4 weeks, or theophyllines and oral or&#xD;
             long-acting inhaled beta2-agonists within 2 weeks of visit 1&#xD;
&#xD;
          -  A change in pulmonary therapy within the 6 weeks prior to the screening visit 1 in&#xD;
             order to control the patient's COPD&#xD;
&#xD;
          -  A history of asthma, allergic rhinitis or atopy or who have a total blood eosinophil&#xD;
             count ≥ 600/mm**3&#xD;
&#xD;
          -  A history of and/or current alcohol abuse and/or drug abuse&#xD;
&#xD;
          -  Use of an investigational drug within one month or six half-lives (which ever is&#xD;
             greater) of the screening visit 1&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</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 23, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 25, 2014</study_first_posted>
  <last_update_submitted>September 25, 2014</last_update_submitted>
  <last_update_submitted_qc>September 25, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">September 26, 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>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_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/NCT02249338
org study id: 543.10
nct id: NCT02249338
lead sponsor: 
Study to investigate the effect of 14-day treatment with BIIL 284 BS on sputum neutrophils
      and specific inflammatory markers in patients with clinically well-defined moderate chronic
      obstructive pulmonary disease (COPD)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Percentage of neutrophils in the induced sputum differential cell count
time frame: Baseline, day 14
measure: Percentage of neutrophils in the spontaneous sputum differential cell count
time frame: Baseline, day 14
measure: Percentage of neutrophils in the induced sputum differential cell count
time frame: Baseline, day 28
measure: Percentage of neutrophils in the spontaneous sputum differential cell count
time frame: Baseline, day 28
measure: Differential cell count in induced sputum
time frame: Baseline, day 14 and 28
description: macrophages, lymphocytes, eosinophils, basophils and epithelial cells
measure: Differential cell count in spontaneous sputum
time frame: Baseline, day 14 and 28
description: macrophages, lymphocytes, eosinophils, basophils and epithelial cells
measure: Wet weight of spontaneous sputum
time frame: Day -6, 0, 6, 13 and 27
description: collected over a 24 hours period the day before each clinic visit
measure: Concentration of myeloperoxidase (MPO) in induced sputum
time frame: Baseline, day 14 and 28
measure: Concentration of myeloperoxidase (MPO) in spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Concentration of neutrophil elastase (NE) in induced sputum
time frame: Baseline, day 14 and 28
measure: Concentration of neutrophil elastase (NE) in spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Concentration of interleukin-8 (IL-8) in induced sputum
time frame: Baseline, day 14 and 28
measure: Concentration of interleukin-8 (IL-8) in spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Concentration of leukotriene B4 (LTB4) in induced sputum
time frame: Baseline, day 14 and 28
measure: Concentration of leukotriene B4 (LTB4) in spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Concentration of albumin in induced sputum
time frame: Baseline, day 14 and 28
measure: Concentration of albumin in spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Sputum bacterial load of induced sputum
time frame: Baseline, day 14 and 28
measure: Sputum bacterial load of spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Sputum chemotactic activity of induced sputum
time frame: Baseline, day 14 and 28
measure: Sputum chemotactic activity of spontaneous sputum
time frame: Baseline, day 14 and 28
measure: Inhibition of blood neutrophil Mac-1 expression
time frame: Day 1 and 14
description: both unstimulated and LTB4-stimulated
measure: Inhibition of blood neutrophil chemotaxis response to LTB4
time frame: Day 1 and 14
measure: Forced expiratory volume in one second (FEV1)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Forced vital capacity (FVC)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Forced expiratory flow (FEF25-75%)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Peak expiratory flow rate (PEFR)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Inspiratory capacity (IC)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Slow vital capacity (SVC)
time frame: Pre-treatment on Day 1, pre- and 30 min post-treatment on day 7 and 14
measure: Changes in COPD symptom score
time frame: Baseline, Day 1, 7 and 14
description: dyspnoea, fatigue, orthopnea, paroxysmal nocturnal dyspnoea and cough
measure: Physician's global evaluation of symptoms assessed on a 4-point scale
time frame: Baseline, Day 14
measure: Number of patients with adverse events
time frame: up to 6 weeks
measure: Plasma concentrations of the analytes
time frame: 30 min before, 90 and 240 min after drug administration on day 1 and 14
arm group label: BIIL 284 BS
arm group type: Experimental
arm group label: Placebo
arm group type: Placebo Comparator
intervention type: Drug
intervention name: BIIL 284 BS
arm group label: BIIL 284 BS
intervention type: Drug
intervention name: Placebo
arm group label: Placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
url: http://trials.boehringer-ingelheim.com
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive