<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/NCT02242240</url>
  </required_header>
  <id_info>
    <org_study_id>1184.2</org_study_id>
    <nct_id>NCT02242240</nct_id>
  </id_info>
  <brief_title>Lung Function Changes Following the Addition of Formoterol to Tiotropium in Patients With Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>Lung Function Changes Following the Addition of Formoterol Inhalation Capsules (12 µ Once or Twice Daily) to Pharmacodynamic Steady State of Once Daily Tiotropium (18 µg) Inhalation Capsule in Patients With COPD</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 establish the lung function effects of added formoterol (12μg QD and BID) during&#xD;
      2-week periods to pharmacodynamic steady state of tiotropium(18μg QD)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>March 2001</start_date>
  <primary_completion_date type="Actual">December 2001</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the curve from time point zero to 24 hours (AUC0-24h) for forced expiratory volume in one second (FEV1)</measure>
    <time_frame>Pre-dose, up to 24 hours after start of treatment</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Area under the curve from 12 to 24 hours (AUC12-24h) for forced expiratory volume in one second (FEV1)</measure>
    <time_frame>12 to 24 hours after start of treatment</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Trough FEV1 response on each pulmonary function test day</measure>
    <time_frame>24 hours after intake of the last morning dose</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough forced vital capacity (FVC) response on each pulmonary function test day</measure>
    <time_frame>Up to 24 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 AUC0-12h on each pulmonary function test day</measure>
    <time_frame>Up to 12 hours after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual FEV1measurements at each time point</measure>
    <time_frame>up to day 58 day after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual FVC measurements at each time point</measure>
    <time_frame>up to day 58 day after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Individual inspiratory capacity (IC) measurements at each time point</measure>
    <time_frame>up to day 58 day after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak expiratory flow rate (PEFR) measured by the patients at home twice daily</measure>
    <time_frame>up to day 79 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Amount of salbutamol therapy used during the treatment period</measure>
    <time_frame>up to day 79 after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of patients with adverse events</measure>
    <time_frame>Up to 93 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC AUC0-12h on each pulmonary function test day</measure>
    <time_frame>up to day 58 day after start of treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FEV1 response on each pulmonary function test day</measure>
    <time_frame>within 3 hours after treatment</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FVC response on each pulmonary function test day</measure>
    <time_frame>within 3 hours after treatment</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">95</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Tiotropium with single dose of formoterol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium with double dose of formoterol</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium with Placebo</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Formoterol twice daily</intervention_name>
    <arm_group_label>Tiotropium with double dose of formoterol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Formoterol once daily</intervention_name>
    <arm_group_label>Tiotropium with single dose of formoterol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium once daily</intervention_name>
    <arm_group_label>Tiotropium with Placebo</arm_group_label>
    <arm_group_label>Tiotropium with double dose of formoterol</arm_group_label>
    <arm_group_label>Tiotropium with single dose of formoterol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <arm_group_label>Tiotropium with Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients must sign an informed consent consistent with international conference of&#xD;
             harmonization (ICH)-good clinical practice (GCP) guidelines prior to participation in&#xD;
             the trial, which includes medication washout and restrictions&#xD;
&#xD;
          -  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&#xD;
                  an FEV1 ≤ 60% of predicted normal and FEV1 ≤ 70% of FVC (Visit 1)&#xD;
&#xD;
                  * Patients who have frequent exacerbations (at least three in the preceding year)&#xD;
                  which could be expected to interfere with the patient's ability to participate in&#xD;
                  the trial should be excluded. The enrollment of patients who have had an&#xD;
                  exacerbation within the six-week period prior to planned study entry should be&#xD;
                  postponed for at least six weeks&#xD;
&#xD;
               -  Predicted normal values will be calculated according to european community for&#xD;
                  coal and steel (ECCS):&#xD;
&#xD;
               -  Males: FEV1 predicted (L) = 4.30 x Height (metres) - 0.029 x Age (years) - 2.49&#xD;
&#xD;
               -  Females: FEV1 predicted (L) = 3.95 x Height (metres) - 0.025 x Age (years) - 2.60&#xD;
&#xD;
          -  Male or female patients 40 years of age or older&#xD;
&#xD;
          -  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;
          -  Patients must be able to perform technically acceptable pulmonary function tests and&#xD;
             must be able to maintain records (Patient Daily Record) during the study period as&#xD;
             required in the protocol&#xD;
&#xD;
          -  Patients must be able to inhale medication from inhalation capsule delivery systems&#xD;
             (the HandiHaler® for the tiotropium and placebo capsules and the Aerolizer® for the&#xD;
             formoterol capsule) and from a metered dose inhaler&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with significant diseases other than COPD will be excluded. A significant&#xD;
             disease is defined as a disease which in the opinion of the investigator may either&#xD;
             put the patient at risk because of participation in the study or a disease which may&#xD;
             influence the results of the study or the patient's ability to participate in the&#xD;
             study&#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&#xD;
&#xD;
          -  All patients with a serum glutamate oxaloacetate transaminase (SGOT) &gt; 80 IU/L, serum&#xD;
             glutamate pyruvate transaminase (SGPT) &gt; 80 IU/L, bilirubin &gt; 17 µmol/L or creatinine&#xD;
             &gt; 110 µmol/L (males) / 95 µmol/L (females) will be excluded regardless of clinical&#xD;
             condition. Repeat laboratory evaluation will not be conducted in these patients&#xD;
&#xD;
          -  Patients with a recent history (i.e., six months or less) of myocardial infarction&#xD;
&#xD;
          -  Patients with any cardiac arrhythmia requiring drug therapy or who have been&#xD;
             hospitalized for heart failure within the past three years&#xD;
&#xD;
          -  Patients with known active tuberculosis&#xD;
&#xD;
          -  Patients on oxygen therapy&#xD;
&#xD;
          -  Patients with history of cystic fibrosis, bronchiectasis, interstitial lung disease,&#xD;
             or pulmonary thromboembolic disease&#xD;
&#xD;
          -  Patients who have undergone thoracotomy with pulmonary resection. Patients with a&#xD;
             history of thoracotomy for other reasons should be evaluated as per exclusion 1&#xD;
&#xD;
          -  Patients with any respiratory infection in the six weeks prior to the Screening Visit&#xD;
             (Visit 1) or during the baseline period&#xD;
&#xD;
          -  Patients with known hypersensitivity to anticholinergic drugs, beta adrenergics,&#xD;
             lactose or any other components of the inhalation capsule delivery system&#xD;
&#xD;
          -  Patients with a history of cancer within the last three years. Patients with treated&#xD;
             basal cell carcinoma are allowed. Patients with successfully treated cancers greater&#xD;
             than five years prior to entry will be allowed&#xD;
&#xD;
          -  Patients with known symptomatic prostatic hypertrophy or bladder neck obstruction&#xD;
&#xD;
          -  Patients with known narrow-angle glaucoma&#xD;
&#xD;
          -  Patients using cromolyn sodium or nedocromil sodium&#xD;
&#xD;
          -  Patients using treated with antihistamines (H1 receptor antagonists)&#xD;
&#xD;
          -  Patients using treated with theophyllines&#xD;
&#xD;
          -  Patients on ß-blocker therapy&#xD;
&#xD;
          -  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;
          -  Pregnant or nursing women or women of childbearing potential not using a medically&#xD;
             approved means of contraception for the previous 3 months (i.e. oral contraceptives,&#xD;
             intrauterine devices, diaphragm or subdermal implants e.g., Norplant®)&#xD;
&#xD;
          -  Patients with a history of asthma, allergic rhinitis or atopy or who have a total&#xD;
             blood eosinophil count ≥ 600 mm3. A repeat eosinophil count will not be conducted in&#xD;
             these patients&#xD;
&#xD;
          -  Patients with significant alcohol or drug abuse within the past two years&#xD;
&#xD;
          -  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;
          -  Patients who are currently in a pulmonary rehabilitation program or who have completed&#xD;
             a program in the six weeks prior to screening (Visit 1)&#xD;
&#xD;
          -  Patients who currently participating in another 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 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>Lung Diseases</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>Formoterol Fumarate</mesh_term>
    <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/NCT02242240
org study id: 1184.2
nct id: NCT02242240
lead sponsor: 
Study to establish the lung function effects of added formoterol (12μg QD and BID) during
      2-week periods to pharmacodynamic steady state of tiotropium(18μg QD)
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area under the curve from time point zero to 24 hours (AUC0-24h) for forced expiratory volume in one second (FEV1)
time frame: Pre-dose, up to 24 hours after start of treatment
measure: Area under the curve from 12 to 24 hours (AUC12-24h) for forced expiratory volume in one second (FEV1)
time frame: 12 to 24 hours after start of treatment
measure: Trough FEV1 response on each pulmonary function test day
time frame: 24 hours after intake of the last morning dose
measure: Trough forced vital capacity (FVC) response on each pulmonary function test day
time frame: Up to 24 hours after start of treatment
measure: FEV1 AUC0-12h on each pulmonary function test day
time frame: Up to 12 hours after start of treatment
measure: Individual FEV1measurements at each time point
time frame: up to day 58 day after start of treatment
measure: Individual FVC measurements at each time point
time frame: up to day 58 day after start of treatment
measure: Individual inspiratory capacity (IC) measurements at each time point
time frame: up to day 58 day after start of treatment
measure: Peak expiratory flow rate (PEFR) measured by the patients at home twice daily
time frame: up to day 79 after start of treatment
measure: Amount of salbutamol therapy used during the treatment period
time frame: up to day 79 after start of treatment
measure: Number of patients with adverse events
time frame: Up to 93 days
measure: FVC AUC0-12h on each pulmonary function test day
time frame: up to day 58 day after start of treatment
measure: Peak FEV1 response on each pulmonary function test day
time frame: within 3 hours after treatment
measure: Peak FVC response on each pulmonary function test day
time frame: within 3 hours after treatment
arm group label: Tiotropium with single dose of formoterol
arm group type: Experimental
arm group label: Tiotropium with double dose of formoterol
arm group type: Experimental
arm group label: Tiotropium with Placebo
arm group type: Experimental
intervention type: Drug
intervention name: Formoterol twice daily
arm group label: Tiotropium with double dose of formoterol
intervention type: Drug
intervention name: Formoterol once daily
arm group label: Tiotropium with single dose of formoterol
intervention type: Drug
intervention name: Tiotropium once daily
arm group label: Tiotropium with Placebo
arm group label: Tiotropium with double dose of formoterol
arm group label: Tiotropium with single dose of formoterol
intervention type: Drug
intervention name: Placebo
arm group label: Tiotropium with 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: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Formoterol Fumarate
mesh term: Tiotropium Bromide