<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/NCT02231177</url>
  </required_header>
  <id_info>
    <org_study_id>1237.3</org_study_id>
    <nct_id>NCT02231177</nct_id>
  </id_info>
  <brief_title>Pharmacokinetics and Safety of BI 1744 CL Plus Tiotropium Bromide in Chronic Obstructive Pulmonary Disease (COPD)</brief_title>
  <official_title>A Randomised, Double-blind, 3-way Crossover Study to Compare Pharmacokinetics and Safety of 10 μg BI 1744 CL Plus 5 μg Tiotropium Bromide Given as Fixed Dose Combination Via the Respimat® Inhaler With the Pharmacokinetics and the Safety of the Single Agents, i.e. 10 μg BI 1744 CL and 5 μg Tiotropium Bromide, Delivered Via the Respimat® Inhaler Following 21 Day-treatment Periods in Patients With Chronic Obstructive Pulmonary Disease (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>
      The purpose of this study is to compare the systemic exposure to BI 1744 BS and tiotropium at&#xD;
      steady state following inhalation of the fixed dose combination (FDC) of 10 μg BI 1744 CL&#xD;
      plus 5 μg tiotropium bromide with the systemic exposure to BI 1744 BS and tiotropium at&#xD;
      steady state following inhalation of the single agents, i.e., 10 μg BI 1744 CL and 5 μg&#xD;
      tiotropium bromide, when administered once-daily via the Respimat® Inhaler for 21 days.&#xD;
&#xD;
      The secondary objectives were to compare the safety and tolerability (adverse events, 12-lead&#xD;
      electrocardiogram recordings, pulmonary function testing) of BI 1744 CL and tiotropium&#xD;
      bromide when administered as fixed dose combination or as single-agent therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>June 2008</start_date>
  <primary_completion_date type="Actual">November 2008</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>AUC(0-1h,ss) of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Ae(0-24h,ss) of Tiotropium</measure>
    <time_frame>Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.</time_frame>
    <description>Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ae(0-24h,ss) of Olodaterol</measure>
    <time_frame>Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.</time_frame>
    <description>Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-6h,ss) of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax,ss of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-2h,ss) of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-4h,ss) of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tz,ss) of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC(0-tz,ss) of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax,ss of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmax,ss of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fe(0-24,ss) of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>fe(0-24,ss) of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin,ss of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin,ss of Olodaterol</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tmin,ss of Tiotropium</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Olodaterol in Plasma</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Concentration of Tiotropium in Plasma</measure>
    <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
    <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC Change From Baseline</measure>
    <time_frame>0:30 and 1:00 h after drug administration on the first day of each treatment period</time_frame>
    <description>Mean change from baseline in forced vital capacity (FVC). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 Change From Baseline</measure>
    <time_frame>0:30 and 1:00 h after drug administration on the first day of each treatment period</time_frame>
    <description>Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG</measure>
    <time_frame>From drug administration until 14 days following the last drug administration</time_frame>
    <description>Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">47</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>BI 1744 CL/Tiotropium FDC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>BI 1744 CL</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1744 CL</intervention_name>
    <arm_group_label>BI 1744 CL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 1744 CL/Tiotropium FDC</intervention_name>
    <arm_group_label>BI 1744 CL/Tiotropium FDC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <arm_group_label>Tiotropium</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All patients must sign an informed consent consistent with International Conference on&#xD;
             Harmonisation (ICH) - Good Clinical Practice (GCP) guidelines and local legislations&#xD;
             prior to any study-related procedures, which includes medication washout and&#xD;
             restrictions&#xD;
&#xD;
          2. All patients must have a diagnosis of COPD and must meet the following spirometric&#xD;
             criteria: Patients must have relatively stable airway obstruction with a&#xD;
             post-bronchodilator forced expiratory volume in one second (FEV1) ≥ 30 % of predicted&#xD;
             normal and &lt; 80% of predicted normal and a post-bronchodilator FEV1 / forced vital&#xD;
             capacity (FVC) &lt; 70% at Visit 1&#xD;
&#xD;
          3. Male or female patients, 40 years of age or older&#xD;
&#xD;
          4. Patients must be current or ex-smokers with a smoking history of more than 10 pack&#xD;
             years&#xD;
&#xD;
          5. Patients must be able to perform technically acceptable pulmonary function tests&#xD;
             during the study period as required in the protocol&#xD;
&#xD;
          6. Patients must be able to inhale medication in a competent manner from the Respimat®&#xD;
             inhaler and from a metered dose inhalator (MDI)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with a significant disease other than COPD; a significant disease is defined&#xD;
             as a disease which, in the opinion of the investigator, may (i) put the patient at&#xD;
             risk because of participation in the study, (ii) influence the results of the study,&#xD;
             or (iii) cause concern regarding the patient's ability to participate in the study&#xD;
&#xD;
          2. Patients with clinically relevant abnormal baseline haematology, blood chemistry or&#xD;
             urinalysis; all patients with a serum glutamic oxaloacetic transaminase (SGOT) &gt; 2.5 x&#xD;
             ULN, serum glutamic pyruvic transaminase (SGPT) &gt; 2.5 x ULN, bilirubin &gt;2x upper limit&#xD;
             of normal (ULN), creatinine &gt;2 x ULN or creatinine clearance &lt; 50 mL/min (Estimation&#xD;
             of Glomerular Filtration Rate (GFR) by using the Cockcroft-Gault Formula) will be&#xD;
             excluded regardless of clinical condition (a repeat laboratory evaluation will not be&#xD;
             conducted in these patients)&#xD;
&#xD;
          3. Patients with a history of asthma or a total blood eosinophil count ≥600/mm3&#xD;
&#xD;
          4. Patients with any of the following conditions:&#xD;
&#xD;
               -  a diagnosis of thyrotoxicosis&#xD;
&#xD;
               -  a diagnosis of paroxysmal tachycardia (&gt;100 beats per minute)&#xD;
&#xD;
               -  a marked baseline prolongation of QT/QTc interval&#xD;
&#xD;
               -  a history of additional risk factors for Torsade de Pointes (TdP) (e.g. heart&#xD;
                  failure, hypokalaemia, family history of Long QT Syndrome)&#xD;
&#xD;
          5. Patients with any of the following conditions:&#xD;
&#xD;
               -  a history of myocardial infarction within 1 year of screening visit (Visit 1)&#xD;
&#xD;
               -  a diagnosis of cardiac arrhythmia, arterial hypertension or coronary heart&#xD;
                  disease&#xD;
&#xD;
               -  known active tuberculosis&#xD;
&#xD;
               -  a malignancy for which patient has undergone resection, radiation therapy or&#xD;
                  chemotherapy within last five years (patients with treated basal cell carcinoma&#xD;
                  are allowed)&#xD;
&#xD;
               -  a history of life-threatening pulmonary obstruction&#xD;
&#xD;
               -  a history of cystic fibrosis&#xD;
&#xD;
               -  clinically evident bronchiectasis&#xD;
&#xD;
               -  a history of significant alcohol or drug abuse&#xD;
&#xD;
          6. Patients who have undergone thoracotomy with pulmonary resection&#xD;
&#xD;
          7. Patients being treated with any of the following concomitant medications:&#xD;
&#xD;
               -  medications that prolong the QT/QTc interval since the effects of BI 1744 CL on&#xD;
                  QT/QTc interval have yet to be fully characterized&#xD;
&#xD;
               -  oral β-adrenergics&#xD;
&#xD;
               -  β-blockers (topical β -blockers for ocular conditions are allowed)&#xD;
&#xD;
               -  oral corticosteroid medication at unstable doses (i.e., less than six weeks on a&#xD;
                  stable dose) or at doses in excess of the equivalent of 10 mg of prednisone per&#xD;
                  day or 20 mg every other day&#xD;
&#xD;
          8. Patients who regularly use daytime oxygen therapy for more than one hour per day and&#xD;
             in the investigator's opinion will be unable to abstain from the use of oxygen therapy&#xD;
             during clinic visits&#xD;
&#xD;
          9. Patients who have completed a pulmonary rehabilitation program in the six weeks prior&#xD;
             to the Screening Visit (Visit 1) or patients who are currently in a pulmonary&#xD;
             rehabilitation program&#xD;
&#xD;
         10. 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;
         11. Patients with known hypersensitivity to β-adrenergics and/or anticholinergic drugs,&#xD;
             benzalkonium chloride, ethylenediaminetetraacetic acid or any other component of the&#xD;
             Respimat® inhalation solution delivery system&#xD;
&#xD;
         12. Pregnant or nursing women&#xD;
&#xD;
         13. Women of childbearing potential not using two highly effective methods of birth&#xD;
             control (one barrier and one non-barrier). Highly effective methods of birth control&#xD;
             are defined as those which result in a low failure rate (i.e. less than 1% per year)&#xD;
             when used consistently and correctly such as implants, injectables, combined oral&#xD;
             contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomised&#xD;
             partner. Female patients will be considered to be of childbearing potential unless&#xD;
             surgically sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal&#xD;
             for at least two years&#xD;
&#xD;
         14. Patients who have previously been randomized in this study or are currently&#xD;
             participating in another study&#xD;
&#xD;
         15. Patients who are unable to comply with pulmonary medication restrictions prior to&#xD;
             randomization&#xD;
&#xD;
         16. According to Inclusion Criterion No. 2, patients with a post-bronchodilator FEV1 of &lt;&#xD;
             30% of predicted normal will always be excluded. Patients with a post-bronchodilator&#xD;
             FEV1 between 30 and 50% of predicted normal will be excluded from the study, if they&#xD;
             display additional symptoms of chronic respiratory insufficiency or right ventricular&#xD;
             insufficiency&#xD;
&#xD;
         17. Patients with narrow angle glaucoma, prostate hyperplasia, or bladder neck obstruction&#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>December 2015</verification_date>
  <study_first_submitted>September 2, 2014</study_first_submitted>
  <study_first_submitted_qc>September 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 4, 2014</study_first_posted>
  <results_first_submitted>June 19, 2015</results_first_submitted>
  <results_first_submitted_qc>December 2, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">January 7, 2016</results_first_posted>
  <last_update_submitted>December 2, 2015</last_update_submitted>
  <last_update_submitted_qc>December 2, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">January 7, 2016</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>Tiotropium Bromide</mesh_term>
    <mesh_term>Olodaterol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A randomised, double-blind, 3-way crossover study, each patient received each of the three treatments for 21 days according to randomisation.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tio+Olo 5/10 μg, Olo 10 μg, Tio 5 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg&#xD;
Olodaterol (Olo) 10 µg.&#xD;
Tiotropium (Tio) 5 µg.</description>
        </group>
        <group group_id="P2">
          <title>Tio+Olo 5/10 μg, Tio 5 μg, Olo 10 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg&#xD;
Tiotropium 5 µg.&#xD;
Olodaterol 10 µg.</description>
        </group>
        <group group_id="P3">
          <title>Olo 10 μg, Tio+Olo 5/10 μg, Tio 5 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Olodaterol 10 µg.&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg&#xD;
Tiotropium 5 µg.</description>
        </group>
        <group group_id="P4">
          <title>Olo 10 μg, Tio 5 μg, Tio+Olo 5/10 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Olodaterol 10 µg.&#xD;
Tiotropium 5 µg.&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg</description>
        </group>
        <group group_id="P5">
          <title>Tio 5 μg, Tio+Olo 5/10 μg, Olo 10 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Tiotropium 5 µg.&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg&#xD;
Olodaterol 10 µg.</description>
        </group>
        <group group_id="P6">
          <title>Tio 5 μg, Olo 10 μg, Tio+Olo 5/10 μg</title>
          <description>Patients received a total of three treatments, the treatments which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Tiotropium 5 µg.&#xD;
Olodaterol 10 µg.&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1 (21 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 2 (21 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 3 (21 Days)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="8"/>
                <participants group_id="P4" count="7"/>
                <participants group_id="P5" count="8"/>
                <participants group_id="P6" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set. All randomised patients who received at least one dose of trial medication were included in the treated set.</population>
      <group_list>
        <group group_id="B1">
          <title>All Subjects</title>
          <description>A randomised, active-controlled, double-blind, 3-way crossover study in patients with COPD (chronic obstructive pulmonary disease). All participants received each of the three treatment arms in a randomly assigned order, the three treatments, which were administered by oral inhalation, from the Respimat inhaler once daily, in the morning for 21 days, were:&#xD;
Fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg&#xD;
Olodaterol 10 µg.&#xD;
Tiotropium 5 µg.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="47"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.8" spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="22"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>AUC(0-1h,ss) of Olodaterol</title>
        <description>Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic (PK) set which included all patients in the treated set who provided at least one of the PK parameters in at least one treatment period and completed the trial without any important protocol violations, it is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-1h,ss) of Olodaterol</title>
          <description>Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic (PK) set which included all patients in the treated set who provided at least one of the PK parameters in at least one treatment period and completed the trial without any important protocol violations, it is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="37"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.67" spread="32.15"/>
                    <measurement group_id="O2" value="4.15" spread="32.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Olodaterol (Tiotropium+Olodaterol 5/10 μg: Olodaterol 10 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.12</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>32.15</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.99</ci_lower_limit>
            <ci_upper_limit>1.27</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax,ss of Olodaterol</title>
        <description>Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax,ss of Olodaterol</title>
          <description>Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.87" spread="27.17"/>
                    <measurement group_id="O2" value="5.28" spread="27.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Olodaterol (Tiotropium+Olodaterol 5/10 μg: Olodaterol 10 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.11</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>27.17</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.01</ci_lower_limit>
            <ci_upper_limit>1.22</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Ae(0-24h,ss) of Tiotropium</title>
        <description>Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Ae(0-24h,ss) of Tiotropium</title>
          <description>Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>ng</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="900.57" spread="20.43"/>
                    <measurement group_id="O2" value="918.63" spread="20.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Tiotropium (Tiotropium+Olodaterol 5/10 μg: Tiotropium 5 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.98</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>20.43</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.91</ci_lower_limit>
            <ci_upper_limit>1.06</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Ae(0-24h,ss) of Olodaterol</title>
        <description>Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Ae(0-24h,ss) of Olodaterol</title>
          <description>Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>ng</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="360.98" spread="19.85"/>
                    <measurement group_id="O2" value="344.17" spread="19.85"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Olodaterol (Tiotropium+Olodaterol 5/10 μg: Olodaterol 10 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.05</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>19.85</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.98</ci_lower_limit>
            <ci_upper_limit>1.13</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-6h,ss) of Tiotropium</title>
        <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-6h,ss) of Tiotropium</title>
          <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)).&#xD;
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="36"/>
                <count group_id="O2" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.97" spread="19.81"/>
                    <measurement group_id="O2" value="33.24" spread="19.81"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Tiotropium (Tiotropium+Olodaterol 5/10 μg: Tiotropium 5 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.90</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>19.81</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.83</ci_lower_limit>
            <ci_upper_limit>0.98</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmax,ss of Tiotropium</title>
        <description>Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax,ss of Tiotropium</title>
          <description>Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15.55" spread="29.92"/>
                    <measurement group_id="O2" value="16.15" spread="29.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Tiotropium (Tiotropium+Olodaterol 5/10 μg : Tiotropium 5 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.96</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>29.92</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.87</ci_lower_limit>
            <ci_upper_limit>1.07</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-2h,ss) of Olodaterol</title>
        <description>Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-2h,ss) of Olodaterol</title>
          <description>Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.52" spread="21.33"/>
                    <measurement group_id="O2" value="8.36" spread="21.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Olodaterol (Tiotropium+Olodaterol 5/10 μg : Olodaterol 10 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>1.02</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>21.33</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.93</ci_lower_limit>
            <ci_upper_limit>1.12</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-4h,ss) of Tiotropium</title>
        <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-4h,ss) of Tiotropium</title>
          <description>Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)).&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="21.92" spread="22.61"/>
                    <measurement group_id="O2" value="24.00" spread="22.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Tiotropium (Tiotropium+Olodaterol 5/10 μg : Tiotropium 5 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.91</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>22.61</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.84</ci_lower_limit>
            <ci_upper_limit>1.00</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-tz,ss) of Olodaterol</title>
        <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-tz,ss) of Olodaterol</title>
          <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.20" spread="96.12"/>
                    <measurement group_id="O2" value="9.25" spread="96.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Olodaterol (Tiotropium+Olodaterol 5/10 μg; Olodaterol 10 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric mean ratio</param_type>
            <param_value>1.32</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>96.12</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.98</ci_lower_limit>
            <ci_upper_limit>1.77</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>AUC(0-tz,ss) of Tiotropium</title>
        <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC(0-tz,ss) of Tiotropium</title>
          <description>Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium.&#xD;
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg*h/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.67" spread="72.08"/>
                    <measurement group_id="O2" value="32.91" spread="72.08"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Comparison of Tiotropium (Tiotropium+Olodaterol 5/10 μg; Tiotropium 5 µg). No formal testing.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Geometric Mean Ratio</param_type>
            <param_value>0.99</param_value>
            <dispersion_type>Standard Deviation</dispersion_type>
            <dispersion_value>72.08</dispersion_value>
            <ci_percent>90</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.79</ci_lower_limit>
            <ci_upper_limit>1.24</ci_upper_limit>
            <estimate_desc>The standard deviation is actually the geometric intra-individual coefficient of variation.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax,ss of Olodaterol</title>
        <description>Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax,ss of Olodaterol</title>
          <description>Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.25" lower_limit="0.050" upper_limit="2.020"/>
                    <measurement group_id="O2" value="0.25" lower_limit="0.083" upper_limit="1.000"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmax,ss of Tiotropium</title>
        <description>Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss).</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax,ss of Tiotropium</title>
          <description>Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss).</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.083" lower_limit="0.033" upper_limit="0.333"/>
                    <measurement group_id="O2" value="0.083" lower_limit="0.033" upper_limit="0.333"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>fe(0-24,ss) of Olodaterol</title>
        <description>Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>fe(0-24,ss) of Olodaterol</title>
          <description>Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>percentage of olodaterol dose</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.62" spread="43.8"/>
                    <measurement group_id="O2" value="3.57" spread="47.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>fe(0-24,ss) of Tiotropium</title>
        <description>Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>fe(0-24,ss) of Tiotropium</title>
          <description>Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>percentage of tiotropium dose</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="43"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.2" spread="41.5"/>
                    <measurement group_id="O2" value="18.6" spread="46.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin,ss of Olodaterol</title>
        <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin,ss of Olodaterol</title>
          <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.30" spread="12.6"/>
                    <measurement group_id="O2" value="2.26" spread="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Cmin,ss of Tiotropium</title>
        <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmin,ss of Tiotropium</title>
          <description>Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.95" spread="14.9"/>
                    <measurement group_id="O2" value="2.89" spread="9.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin,ss of Olodaterol</title>
        <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin,ss of Olodaterol</title>
          <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="45"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="0.0" upper_limit="24.0"/>
                    <measurement group_id="O2" value="1.01" lower_limit="0.0" upper_limit="12.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tmin,ss of Tiotropium</title>
        <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmin,ss of Tiotropium</title>
          <description>Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>h</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="45"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.00" lower_limit="0.0" upper_limit="24.0"/>
                    <measurement group_id="O2" value="8.00" lower_limit="0.33" upper_limit="24.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Concentration of Olodaterol in Plasma</title>
        <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Olodaterol in Plasma</title>
          <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="43"/>
                <count group_id="O2" value="40"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>C(0.333_8) (N=38, 34)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.09" spread="48.0"/>
                    <measurement group_id="O2" value="4.48" spread="48.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C(0.333_14,ss) (N=41, 38)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.13" spread="41.4"/>
                    <measurement group_id="O2" value="4.66" spread="52.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C(0.333_21,ss) (N=43, 40)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.23" spread="53.7"/>
                    <measurement group_id="O2" value="4.80" spread="54.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Concentration of Tiotropium in Plasma</title>
        <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
        <time_frame>Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.</time_frame>
        <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Concentration of Tiotropium in Plasma</title>
          <description>Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.&#xD;
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.</description>
          <population>Pharmacokinetic set which is however restricted to patients with evaluable data for this endpoint.</population>
          <units>pg/mL</units>
          <param>Geometric Mean</param>
          <dispersion>Geometric Coefficient of Variation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="46"/>
                <count group_id="O2" value="44"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>C(0.333_8) (N=40, 38)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.90" spread="60.7"/>
                    <measurement group_id="O2" value="9.58" spread="52.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C(0.333_14,ss) (N=43, 40)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.08" spread="53.3"/>
                    <measurement group_id="O2" value="9.02" spread="60.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>C(0.333_21,ss) (N=46, 44)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.34" spread="53.2"/>
                    <measurement group_id="O2" value="9.21" spread="58.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FVC Change From Baseline</title>
        <description>Mean change from baseline in forced vital capacity (FVC). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
        <time_frame>0:30 and 1:00 h after drug administration on the first day of each treatment period</time_frame>
        <population>Treated Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>FVC Change From Baseline</title>
          <description>Mean change from baseline in forced vital capacity (FVC). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
          <population>Treated Set.</population>
          <units>L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0:30 h after drug administration (N=47, 47, 47)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.485" spread="0.354"/>
                    <measurement group_id="O2" value="0.450" spread="0.406"/>
                    <measurement group_id="O3" value="0.436" spread="0.321"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1:00 h after drug administration (N=47, 46, 47)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.547" spread="0.409"/>
                    <measurement group_id="O2" value="0.522" spread="0.375"/>
                    <measurement group_id="O3" value="0.470" spread="0.387"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FEV1 Change From Baseline</title>
        <description>Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
        <time_frame>0:30 and 1:00 h after drug administration on the first day of each treatment period</time_frame>
        <population>Treated Set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 Change From Baseline</title>
          <description>Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test.&#xD;
The baseline value was measured pre-dose on day 1 of the first treatment period.</description>
          <population>Treated Set.</population>
          <units>L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>0:30 h after drug administration (N=47, 47, 47)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.275" spread="0.202"/>
                    <measurement group_id="O2" value="0.292" spread="0.233"/>
                    <measurement group_id="O3" value="0.271" spread="0.211"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>1:00 h after drug administration (N=47, 46, 47)</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.335" spread="0.250"/>
                    <measurement group_id="O2" value="0.357" spread="0.237"/>
                    <measurement group_id="O3" value="0.284" spread="0.206"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG</title>
        <description>Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered.</description>
        <time_frame>From drug administration until 14 days following the last drug administration</time_frame>
        <population>Treated Set. All randomised patients who received at least one dose of trial medication were included in the treated set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol 5/10 μg</title>
            <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O2">
            <title>Olodaterol 10 µg</title>
            <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium 5 µg</title>
            <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG</title>
          <description>Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered.</description>
          <population>Treated Set. All randomised patients who received at least one dose of trial medication were included in the treated set.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="47"/>
                <count group_id="O3" value="47"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From drug administration until 14 days following the last drug administration were assigned to the last study treatment administered, upto 37 days.</time_frame>
      <desc>At each visit, all adverse events, regardless of causality, were recorded on the adverse event case report form page after discussion with the patient.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tiotropium+Olodaterol 5/10 μg</title>
          <description>Oral inhalation of fixed dose combination (FDC) of Tiotropium 5 µg and Olodaterol 10 µg (Tiotropium: 2.5 µg per actuation and Olodaterol: 5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
        </group>
        <group group_id="E2">
          <title>Olodaterol 10 µg</title>
          <description>Oral inhalation of Olodaterol 10 µg (5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
        </group>
        <group group_id="E3">
          <title>Tiotropium 5 µg</title>
          <description>Oral inhalation of Tiotropium 5 µg (2.5 µg per actuation), 2 puffs from the Respimat inhaler, once daily, in the morning, for 21 days.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 11.1</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="47"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="47"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="47"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Additional secondary endpoints were listed in the original protocol, but according to internal rules, descriptive statistics would not be calculated unless data from at least 2/3rds of all subjects were available.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02231177
org study id: 1237.3
nct id: NCT02231177
lead sponsor: 
The purpose of this study is to compare the systemic exposure to BI 1744 BS and tiotropium at
      steady state following inhalation of the fixed dose combination (FDC) of 10 μg BI 1744 CL
      plus 5 μg tiotropium bromide with the systemic exposure to BI 1744 BS and tiotropium at
      steady state following inhalation of the single agents, i.e., 10 μg BI 1744 CL and 5 μg
      tiotropium bromide, when administered once-daily via the Respimat® Inhaler for 21 days.

      The secondary objectives were to compare the safety and tolerability (adverse events, 12-lead
      electrocardiogram recordings, pulmonary function testing) of BI 1744 CL and tiotropium
      bromide when administered as fixed dose combination or as single-agent therapy.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double
measure: AUC(0-1h,ss) of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the concentration time curve of Olodaterol in plasma over the time interval t1=0 to t2=1 hour at steady state (AUC(0-1h,ss)).
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Olodaterol. Based on the given definition AUC(0-1h,ss) was selected as primary endpoint.
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: Cmax,ss of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Maximum measured concentration of Olodaterol in plasma at steady state (Cmax,ss).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: Ae(0-24h,ss) of Tiotropium
time frame: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.
description: Amount of Tiotropium that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: Ae(0-24h,ss) of Olodaterol
time frame: Intervals 0-4, 4-8, 8-12 and 12-24 hours on Day 21 of the actual treatment period.
description: Amount of Olodaterol that was eliminated in urine at steady state from time point 0 to 24 h post-inhalation (Ae(0-24h,ss)).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: AUC(0-6h,ss) of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=6 h at steady state (AUC(0-6h,ss)).
As plasma concentrations were not expected to be quantifiable over the complete dosing interval in all patients, t2 was defined as the time-point where at least 2/3 of the patients reveal quantifiable plasma concentrations of Tiotropium. Based on the given definition AUC(0-6h,ss) was selected as secondary endpoint.
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: Cmax,ss of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Maximum measured concentration of Tiotropium in plasma at steady state (Cmax,ss).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: AUC(0-2h,ss) of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the concentration time curve of Olodaterol in plasma over the time interval 0 to 2 hours at steady state (AUC(0-2h,ss)).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: AUC(0-4h,ss) of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the concentration time curve of Tiotropium in plasma over the time interval t1=0 to t2=4 h at steady state (AUC(0-4h,ss)).
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: AUC(0-tz,ss) of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Olodaterol.
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: AUC(0-tz,ss) of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Area under the plasma concentration-time curve at steady state over the time interval from 0 to the time of the last quantifiable data point (AUC(0-tz)) for Tiotropium.
The displayed values show adjusted gMeans and intra-subject variabilities calculated from the statistical model (ANOVA).
measure: Tmax,ss of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Time from dosing to the maximum concentration of Olodaterol in plasma at steady state (tmax,ss).
measure: Tmax,ss of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Time from dosing to the maximum concentration of Tiotropium in plasma at steady state (tmax,ss).
measure: fe(0-24,ss) of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Fraction of Olodaterol eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: fe(0-24,ss) of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Fraction of Tiotropium eliminated in urine from 0 to 24 hours at steady state (fe(0-24,ss)).
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: Cmin,ss of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: Cmin,ss of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (Cmin,ss).
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: Tmin,ss of Olodaterol
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)
measure: Tmin,ss of Tiotropium
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Time from last dosing to the minimum concentration of the analyte in plasma at steady state over a uniform dosing interval (tmin,ss)
measure: Concentration of Olodaterol in Plasma
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: Concentration of Tiotropium in Plasma
time frame: Within 30 min before drug administration and 0:02, 0:05, 0:10, 0:15, 0:20, 0:40, 1:00, 2:00, 4:00, 6:00, 8:00, 12:00, 24:00 hours after drug administration on Day 21 of the actual treatment period.
description: Concentration of the analyte in plasma at 0.333 hours (20 minutes) after the 8th, 14th and 21st dose, C(0.333_8), C(0.333_14,ss) and C(0.333_21,ss) respectively. As steady state was anticipated to be reached by day 14 at the latest, the index 'ss' was used for days 14 and 21.
The displayed values show gMeans and inter-subject variabilities calculated from descriptive statistics.
measure: FVC Change From Baseline
time frame: 0:30 and 1:00 h after drug administration on the first day of each treatment period
description: Mean change from baseline in forced vital capacity (FVC). Pulmonary function test.
The baseline value was measured pre-dose on day 1 of the first treatment period.
measure: FEV1 Change From Baseline
time frame: 0:30 and 1:00 h after drug administration on the first day of each treatment period
description: Mean change from baseline in forced expiratory volume in one second (FEV1). Pulmonary function test.
The baseline value was measured pre-dose on day 1 of the first treatment period.
measure: Clinical Relevant Abnormalities in Vital Signs, Physical Examination, Blood Chemistry, Haematology, Urinanalysis and ECG
time frame: From drug administration until 14 days following the last drug administration
description: Clinically relevant abnormalities in vital signs (blood pressure and pulse rate), physical examination, blood chemistry, haematology, urinanalysis and ECG. New abnormal findings or worsening of baseline conditions were reported as Adverse Events. Any adverse events which occurred within 14 days following the last drug administration were assigned to the last study treatment administered.
arm group label: BI 1744 CL/Tiotropium FDC
arm group type: Experimental
arm group label: BI 1744 CL
arm group type: Active Comparator
arm group label: Tiotropium
arm group type: Active Comparator
intervention type: Drug
intervention name: BI 1744 CL
arm group label: BI 1744 CL
intervention type: Drug
intervention name: BI 1744 CL/Tiotropium FDC
arm group label: BI 1744 CL/Tiotropium FDC
intervention type: Drug
intervention name: Tiotropium
arm group label: Tiotropium
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: Tiotropium Bromide
mesh term: Olodaterol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Additional secondary endpoints were listed in the original protocol, but according to internal rules, descriptive statistics would not be calculated unless data from at least 2/3rds of all subjects were available.
point of contact: 