<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/NCT01703845</url>
  </required_header>
  <id_info>
    <org_study_id>1237.24</org_study_id>
    <nct_id>NCT01703845</nct_id>
  </id_info>
  <brief_title>A Study to Characterize Pharmacokinetics of Tiotropium + Olodaterol Fixed-dose Combination in Japanese Patients With COPD.</brief_title>
  <official_title>A Randomised, Open-label, Parallel-group Trial to Assess Pharmacokinetics and Safety of Tiotropium + Olodaterol Fixed-dose Combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) Delivered by the RESPIMAT Inhaler After 3 Weeks Once Daily Treatment in Japanese 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 primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol&#xD;
      fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3&#xD;
      weeks once daily treatment in Japanese patients with COPD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>October 2012</start_date>
  <completion_date type="Actual">March 2013</completion_date>
  <primary_completion_date type="Actual">March 2013</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cmax,ss (Olodaterol)</measure>
    <time_frame>15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21</time_frame>
    <description>Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCt1-t2,ss (Olodaterol)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
    <description>Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-tz,ss (Olodaterol)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
    <description>Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax,ss (Olodaterol)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21</time_frame>
    <description>Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aet1-t2,ss (Olodaterol)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fe t1-t2,ss (Olodaterol)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR,t1-t2,ss (Olodaterol)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cmax,ss (Tiotropium)</measure>
    <time_frame>15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21</time_frame>
    <description>Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUCt1-t2,ss (Tiotropium)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21</time_frame>
    <description>Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>AUC0-tz,ss (Tiotropium)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
    <description>Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Tmax,ss (Tiotropium)</measure>
    <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21</time_frame>
    <description>Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Aet1-t2,ss (Tiotropium)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>fe t1-t2,ss (Tiotropium)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>CLR,t1-t2,ss (Tiotropium)</measure>
    <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
    <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.&#xD;
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)</measure>
    <time_frame>up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose</time_frame>
    <description>Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG</measure>
    <time_frame>up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose</time_frame>
    <description>Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.&#xD;
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Tiotropium + Olodaterol (high dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tiotropium + Olodaterol (low dose)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium (high dose) + Olodaterol</intervention_name>
    <description>Tiotropium + Olodaterol solution for inhalation</description>
    <arm_group_label>Tiotropium + Olodaterol (high dose)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium (low dose) + Olodaterol</intervention_name>
    <description>Tiotropium + Olodaterol solution for inhalation</description>
    <arm_group_label>Tiotropium + Olodaterol (low dose)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. Diagnosis of chronic obstructive pulmonary disease&#xD;
&#xD;
          2. Relatively stable airway obstruction with post FEV1=&lt;30% of predicted normal and&lt; 80%&#xD;
             predicted normal and post FEV1/FVC &lt;70%&#xD;
&#xD;
          3. Male or female Japanese patients, 40 years of age or older&#xD;
&#xD;
          4. Smoking history of more than 10 pack years&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Significant disease other than COPD&#xD;
&#xD;
          2. Clinically relevant abnormal lab values&#xD;
&#xD;
          3. History of asthma&#xD;
&#xD;
          4. Diagnosis of thyrotoxicosis&#xD;
&#xD;
          5. Diagnosis of paroxysmal tachycardia&#xD;
&#xD;
          6. A marked baseline prolongation of QT/QTc interval&#xD;
&#xD;
          7. A history of additional risk factors for Torsade de Pointes (TdP)&#xD;
&#xD;
          8. History of myocardial infarction within 1 year of screening visit&#xD;
&#xD;
          9. Unstable or life-threatening cardiac arrhythmia&#xD;
&#xD;
         10. Hospitalization for heart failure within the past year&#xD;
&#xD;
         11. Known active tuberculosis&#xD;
&#xD;
         12. Malignancy for which patient has undergone resection, radiation therapy or&#xD;
             chemotherapy within last five years&#xD;
&#xD;
         13. History of life-threatening pulmonary obstruction&#xD;
&#xD;
         14. History of cystic fibrosis&#xD;
&#xD;
         15. Clinically evident bronchiectasis&#xD;
&#xD;
         16. History of significant alcohol or drug abuse&#xD;
&#xD;
         17. Thoracotomy with pulmonary resection&#xD;
&#xD;
         18. Oral ß-adrenergics&#xD;
&#xD;
         19. Oral corticosteroid medication at unstable doses&#xD;
&#xD;
         20. Regular use of daytime oxygen therapy for more than one hour per day&#xD;
&#xD;
         21. Pulmonary rehabilitation program in the six weeks prior to the screening visit&#xD;
&#xD;
         22. Investigational drug within one month or six half lives (whichever is greater) prior&#xD;
             to screening visit&#xD;
&#xD;
         23. Known hypersensitivity to ß-adrenergic drugs, anticholinergics, BAC, EDTA&#xD;
&#xD;
         24. Pregnant or nursing women&#xD;
&#xD;
         25. Women of childbearing potential not using a highly effective method of birth control&#xD;
&#xD;
         26. Patients who have previously been randomized in this study or are currently&#xD;
             participating in another study&#xD;
&#xD;
         27. Patients who are unable to comply with pulmonary medication restrictions&#xD;
&#xD;
         28. Patients with narrow-angle glaucoma or micturition disorder due to prostatic&#xD;
             hyperplasia etc&#xD;
&#xD;
         29. Patients being treated with medications that prolong the QT/QTc interval&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>1237.24.24001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Toshima-ku, Tokyo</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>June 2015</verification_date>
  <study_first_submitted>October 8, 2012</study_first_submitted>
  <study_first_submitted_qc>October 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 11, 2012</study_first_posted>
  <results_first_submitted>June 19, 2015</results_first_submitted>
  <results_first_submitted_qc>June 19, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 15, 2015</results_first_posted>
  <last_update_submitted>June 19, 2015</last_update_submitted>
  <last_update_submitted_qc>June 19, 2015</last_update_submitted_qc>
  <last_update_posted type="Estimate">July 15, 2015</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tiotropium Bromide</mesh_term>
    <mesh_term>Olodaterol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>This is a randomised, open-label, parallel group trial in which 3 weeks of randomised treatment are preceded by 2-week screening period and followed by 3-week follow-up period.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tiotropium + Olodaterol (5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="16">started are actually the randomized</participants>
                <participants group_id="P2" count="16">started are actually the randomized</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="16"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>other than stated above</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS) includes all randomised patients who received at least one dose of trial medication.</population>
      <group_list>
        <group group_id="B1">
          <title>Tiotropium + Olodaterol (5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="16"/>
            <count group_id="B2" value="16"/>
            <count group_id="B3" value="32"/>
          </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="63.4" spread="10.5"/>
                    <measurement group_id="B2" value="69.4" spread="7.8"/>
                    <measurement group_id="B3" value="66.4" spread="9.6"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Cmax,ss (Olodaterol)</title>
        <description>Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set was defined as all treated patients who have at least 1 PK parameter in the treatment period without PK related important protocol violations. Two patients prematurely stopped the trial medication and had no PK measurement at Visit 3 (day 21) and were excluded from the PK set. Thus, the PK set included 30 patients.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax,ss (Olodaterol)</title>
          <description>Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set was defined as all treated patients who have at least 1 PK parameter in the treatment period without PK related important protocol violations. Two patients prematurely stopped the trial medication and had no PK measurement at Visit 3 (day 21) and were excluded from the PK set. Thus, the PK set included 30 patients.</population>
          <units>picogram/milliliter (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="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.33" spread="53.7"/>
                    <measurement group_id="O2" value="2.82" spread="106"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCt1-t2,ss (Olodaterol)</title>
        <description>Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCt1-t2,ss (Olodaterol)</title>
          <description>Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.94" spread="29.9"/>
                    <measurement group_id="O2" value="8.14" spread="65.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC0-tz,ss (Olodaterol)</title>
        <description>Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-tz,ss (Olodaterol)</title>
          <description>Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="12"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.94" spread="29.9"/>
                    <measurement group_id="O2" value="6.85" spread="105"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tmax,ss (Olodaterol)</title>
        <description>Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax,ss (Olodaterol)</title>
          <description>Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="13"/>
                <count group_id="O2" value="15"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.183" lower_limit="0.100" upper_limit="0.333"/>
                    <measurement group_id="O2" value="0.217" lower_limit="0.100" upper_limit="2.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aet1-t2,ss (Olodaterol)</title>
        <description>Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Aet1-t2,ss (Olodaterol)</title>
          <description>Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>nanogram (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="13"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74.8" spread="100"/>
                    <measurement group_id="O2" value="50.0" spread="123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>fe t1-t2,ss (Olodaterol)</title>
        <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>fe t1-t2,ss (Olodaterol)</title>
          <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>percentage of 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="13"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.50" spread="100"/>
                    <measurement group_id="O2" value="0.999" spread="123"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>CLR,t1-t2,ss (Olodaterol)</title>
        <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>CLR,t1-t2,ss (Olodaterol)</title>
          <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>mL/min</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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="152" spread="48.7"/>
                    <measurement group_id="O2" value="148" spread="42.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)</title>
        <description>Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.</description>
        <time_frame>up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose</time_frame>
        <population>Treated Set (TS) includes all randomised patients who received at least one dose of trial medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)</title>
          <description>Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.</description>
          <population>Treated Set (TS) includes all randomised patients who received at least one dose of trial medication.</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Cmax,ss (Tiotropium)</title>
        <description>Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Cmax,ss (Tiotropium)</title>
          <description>Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>picogram/milliliter (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="13"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.5" spread="92.0"/>
                    <measurement group_id="O2" value="6.49" spread="50.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUCt1-t2,ss (Tiotropium)</title>
        <description>Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>AUCt1-t2,ss (Tiotropium)</title>
          <description>Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="12"/>
                <count group_id="O2" value="11"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.8" spread="50.7"/>
                    <measurement group_id="O2" value="7.00" spread="52.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>AUC0-tz,ss (Tiotropium)</title>
        <description>Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>AUC0-tz,ss (Tiotropium)</title>
          <description>Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="12"/>
                <count group_id="O2" value="13"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.3" spread="44.8"/>
                    <measurement group_id="O2" value="7.99" spread="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Tmax,ss (Tiotropium)</title>
        <description>Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Tmax,ss (Tiotropium)</title>
          <description>Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</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="13"/>
                <count group_id="O2" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.100" lower_limit="0.100" upper_limit="0.333"/>
                    <measurement group_id="O2" value="0.100" lower_limit="0.083" upper_limit="0.183"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Aet1-t2,ss (Tiotropium)</title>
        <description>Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Aet1-t2,ss (Tiotropium)</title>
          <description>Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>nanogram (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="13"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="336" spread="119"/>
                    <measurement group_id="O2" value="122" spread="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>fe t1-t2,ss (Tiotropium)</title>
        <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>fe t1-t2,ss (Tiotropium)</title>
          <description>Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>percentage of 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="13"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.72" spread="119"/>
                    <measurement group_id="O2" value="4.89" spread="118"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>CLR,t1-t2,ss (Tiotropium)</title>
        <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.&#xD;
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).</description>
        <time_frame>from 0 to 4 hours following drug administration on day 21</time_frame>
        <population>The Pharmacokinetic (PK) set.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>CLR,t1-t2,ss (Tiotropium)</title>
          <description>Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).&#xD;
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.&#xD;
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).</description>
          <population>The Pharmacokinetic (PK) set.</population>
          <units>mL/min</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="12"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="292" spread="44.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG</title>
        <description>Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.&#xD;
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.</description>
        <time_frame>up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose</time_frame>
        <population>The treated Set (TS).</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium + Olodaterol (5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
            <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC).The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG</title>
          <description>Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.&#xD;
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.</description>
          <population>The treated Set (TS).</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="16"/>
                <count group_id="O2" value="16"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>AEs reported related to vital signs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>AEs reported related to ECG</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Haematuria</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood creatine phosphokinase increased</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Blood urine present</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to 44 days (23 days maximum number of days a study treatment was used after first intake and 21 days follow-up)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tiotropium + Olodaterol (5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 5 microgram (µg) (high dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Tiotropium + Olodaterol (2.5µg/5µg)</title>
          <description>Oral inhalation of tiotropium 2.5 microgram (µg) (low dose) + olodaterol solution 5µg fixed-dose combination (FDC). The patients inhale 2 puffs from the RESPIMAT inhaler, once a day, in the morning up to 3 weeks.</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="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MEDDRA 16.0</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="4" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Blood creatine phosphokinase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
              <event>
                <sub_title>Blood urine present</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="16"/>
              </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>
    <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/NCT01703845
org study id: 1237.24
nct id: NCT01703845
lead sponsor: 
The primary objective of this study is to assess pharmacokinetics of tiotropium + olodaterol
      fixed-dose combination (2.5 µg/ 5 µg, 5 µg/ 5 µg) delivered by the RESPIMAT inhaler after 3
      weeks once daily treatment in Japanese patients with COPD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Cmax,ss (Olodaterol)
time frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
description: Maximum measured concentration of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: AUCt1-t2,ss (Olodaterol)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
description: Area under the concentration-time curve of olodaterol in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: AUC0-tz,ss (Olodaterol)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
description: Area under the concentration-time curve of olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: Tmax,ss (Olodaterol)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3 and 4 hours (h) following drug administration on day 21
description: Time from dosing to the maximum concentration of Olodaterol after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: Aet1-t2,ss (Olodaterol)
time frame: from 0 to 4 hours following drug administration on day 21
description: Amount of olodaterol that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: fe t1-t2,ss (Olodaterol)
time frame: from 0 to 4 hours following drug administration on day 21
description: Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: CLR,t1-t2,ss (Olodaterol)
time frame: from 0 to 4 hours following drug administration on day 21
description: Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: Cmax,ss (Tiotropium)
time frame: 15 minutes (min) pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 hours (h) following drug administration on day 21
description: Maximum measured concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (Cmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: AUCt1-t2,ss (Tiotropium)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1 and 2 h following drug administration on day 21
description: Area under the concentration-time curve of tiotropium in plasma after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 2 hours at steady state (AUCt1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: AUC0-tz,ss (Tiotropium)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, and 4 h following drug administration on day 21
description: Area under the concentration-time curve of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma over the time interval from 0 to the time of the last quantifiable data point at steady state (AUC0-tz,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: Tmax,ss (Tiotropium)
time frame: 15 min pre-dose and 5, 10, 20, 40 min, 1, 2, 3, 4 hours following drug administration on day 21
description: Time from dosing to the maximum concentration of tiotropium after multiple inhaled administration of tiotropium+olodaterol in plasma at steady state (tmax,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: Aet1-t2,ss (Tiotropium)
time frame: from 0 to 4 hours following drug administration on day 21
description: Amount of tiotropium that is eliminated in urine after multiple inhaled administration of tiotropium+olodaterol over the time interval 0 to 4 hours at steady state (Aet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: fe t1-t2,ss (Tiotropium)
time frame: from 0 to 4 hours following drug administration on day 21
description: Fraction eliminated in urine from the time point t1 (0 h) to time point t2 (4 h) at steady state (fet1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
measure: CLR,t1-t2,ss (Tiotropium)
time frame: from 0 to 4 hours following drug administration on day 21
description: Renal clearance from the time point t1 (0 h) until the time point t2 (4 h) at steady state (CLR,t1-t2,ss).
Per Protocol there are no primary endpoints defined. Therefore this pharmacokinetic endpoint was selected for primary outcome measure type.
Plasma concentration of tiotropium could not be quantified up to 4 hours for Tiotropium + Olodaterol (2.5μg/5μg).
measure: Number of Participants With Adverse Events (Including Assessment Based on Physical Examination)
time frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
description: Outcome data show are the number of patients with an adverse event including the assessment based on physical examination.
measure: Number of Participants With Clinically Relevant Abnormalities in Vital Signs, Clinical Laboratory Tests and ECG
time frame: up to 6 weeks (3 weeks treatment and 3 weeks follow-up) post dose
description: Outcome data show are the number of participants with clinically relevant abnormalities reported as an adverse event (AE) related to the vital signs (pulse rate and blood pressure in supine position), clinical laboratory (routine blood chemistry, haematology, and urinalysis) tests and ECG (12-lead holter monitoring Electrocardiography). Relevant findings or worsening of baseline conditions were reported as adverse events.
There were no clinically relevant abnormalities reported as an AE related to the vital signs and ECG.
arm group label: Tiotropium + Olodaterol (high dose)
arm group type: Experimental
description: Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
arm group label: Tiotropium + Olodaterol (low dose)
arm group type: Experimental
description: Tiotropium and Olodaterol fixed dose combination (FDC) solution for inhalation - RESPIMAT
intervention type: Drug
intervention name: Tiotropium (high dose) + Olodaterol
description: Tiotropium + Olodaterol solution for inhalation
arm group label: Tiotropium + Olodaterol (high dose)
intervention type: Drug
intervention name: Tiotropium (low dose) + Olodaterol
description: Tiotropium + Olodaterol solution for inhalation
arm group label: Tiotropium + Olodaterol (low dose)
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
country: Japan
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Tiotropium Bromide
mesh term: Olodaterol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 