<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/NCT01696071</url>
  </required_header>
  <id_info>
    <org_study_id>205.441</org_study_id>
    <secondary_id>2012-001873-10</secondary_id>
    <nct_id>NCT01696071</nct_id>
  </id_info>
  <brief_title>Comparison of Two Daily Dose Regimens of Tiotropium 5 µg Once Daily and Tiotropium 2.5 µg Twice Daily for 4 Weeks on Top of Maintenance Therapy With Inhaled Corticosteroid Controller Medication</brief_title>
  <official_title>A Randomised, Double- Blind, 2 Way Cross-over Study to Determine 24-hour FEV1-time Profile of Inhaled Tiotropium, Delivered Via the Respimat Inhaler, After 4 Weeks of Once Daily [5 mcg in the Evening (2 Actuations of 2.5 mcg)] or Twice Daily [2.5 mcg in the Morning and Evening (2 Actuations of 1.25 mcg)] Administration in Patients With Moderate Persistent Asthma.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Pfizer</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Determine the 24-hour FEV1-profile of tiotropium solution for inhalation after 4 weeks&#xD;
      treatment periods of 5 mcg tiotropium administered once daily in the evening and 2.5 mcg&#xD;
      tiotropium administered twice daily (morning and evening). In addition compare the 24 hours&#xD;
      pharmacokinetic profile of 5 mcg tiotropium administered once daily and 2.5mcg tiotropium&#xD;
      administered twice daily in pharmacokinetic sub-investigation.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">June 2013</completion_date>
  <primary_completion_date type="Actual">June 2013</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 - 24h (AUC 0-24) Response.</measure>
    <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>FEV1 AUC0-12h Response</measure>
    <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FEV1 AUC12-24h Response</measure>
    <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FEV1 Response.</measure>
    <time_frame>10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks.</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FEV1 was defined as the highest FEV1 reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FEV1 Peak0-24h). The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough FEV1 (L) Response.</measure>
    <time_frame>10 minutes (min) prior to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FEV1 was defined as the FEV1 value just prior to the last evening dose of study medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Forced Vital Capacity (FVC) AUC0-24h Response</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC AUC0-12h Response</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC AUC12-24h Response</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FVC Response</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FVC was defined as the highest FVC reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FVC Peak0-24h).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough FVC Responses</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FVC was defined as the FVC value just prior to the last evening dose of study medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Expiratory Flow (PEF) AUC0-24h Response</measure>
    <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
    <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres per minute.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">98</enrollment>
  <condition>Asthma</condition>
  <arm_group>
    <arm_group_label>Treatment A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 puffs of daily dose (5 mcg) in the evening and 2 puffs of matching placebo in the morning via Respimat inhaler</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Treatment B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 puffs of half daily dose (2.5 mcg) twice daily, in the evening and in the morning via Respimat inhaler</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium 5 mcg qd</intervention_name>
    <description>2 puffs (2.5 mcg each) in the evening 5 mcg in total and 2 puffs of matching placebo in the morning</description>
    <arm_group_label>Treatment A</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium 2.5 mcg bid</intervention_name>
    <description>2 puffs (1.25 mcg each) twice daily, in the evening and in the morning, 5 mcg in total</description>
    <arm_group_label>Treatment B</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. All patients must sign and date an Informed Consent Form consistent with ICH-GCP&#xD;
             guidelines and local legislation prior to participation in the trial.&#xD;
&#xD;
          2. Male or female patients aged at least 18 years at Visit 0 but not more than 75 years&#xD;
             at Visit 0.&#xD;
&#xD;
          3. All patients must have at least a 3 months history of asthma at the time of enrolment&#xD;
             (signing ICF) into the trial. The initial diagnosis of asthma must have been made&#xD;
             before the patient's age of 40.&#xD;
&#xD;
          4. All patients must have a pre-bronchodilator FEV1 = 60% predicted and = 90% of&#xD;
             predicted normal at Visit 1.Variation of absolute pre-bronchodilator FEV1 values at&#xD;
             Visit 1 and Visit 2 must be within ± 30%.&#xD;
&#xD;
          5. Patient's diagnosis of asthma has to be confirmed at Visit 1 with bronchodilator&#xD;
             reversibility (ie 10 minutes prior to and 15-30 minutes after inhalation of 400 µg&#xD;
             salbutamol) defined as an FEV1 increase of = 12% and = 200 mL.&#xD;
&#xD;
          6. All patients must have a diagnosis of moderate persistent asthma and must be&#xD;
             symptomatic despite their current maintenance treatment with medium doses of ICS.&#xD;
&#xD;
          7. All patients must be symptomatic at Visit 1and Visit 2 as defined by an ACQ mean score&#xD;
             of = 1.5.&#xD;
&#xD;
          8. All patients must have maintenance treatment with stable medium daily dose of ICS for&#xD;
             at least 4 weeks prior to Visit 1.&#xD;
&#xD;
          9. Patients must be never-smokers or ex-smokers who stopped smoking at least one year&#xD;
             prior to enrolment (Visit 0) and who have a smoking history of less than 10 pack-years&#xD;
             at Visit 0.&#xD;
&#xD;
         10. Patients must be able to use the Respimat inhaler correctly.&#xD;
&#xD;
         11. Patients must be able to perform all trial related procedures including technically&#xD;
             acceptable pulmonary function tests and use of the AM3 (e-diary) compliance of at&#xD;
             least 80% is required.&#xD;
&#xD;
         12. Patients taking a chronic pulmonary medication allowed by the study protocol must be&#xD;
             willing to continue this therapy for the entire duration of the study (exception:&#xD;
             times of acute disease deterioration).&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients with a significant disease other than asthma. A significant disease is&#xD;
             defined as a disease which, in the opinion of the investigator, may (i) put the&#xD;
             patient at risk because of participation in the trial, or (ii) influence the results&#xD;
             of the trial, or (iii) cause concern regarding the patient's ability to participate in&#xD;
             the trial.&#xD;
&#xD;
          2. Patients with a clinically relevant abnormal screening hematology or blood chemistry&#xD;
             at Visit 1 if the abnormality defines a significant disease as defined in exclusion&#xD;
             criterion no. 1.&#xD;
&#xD;
          3. Patients requiring more than 12 puffs of rescue medication (salbutamol MDI) per 24&#xD;
             hours for more than 2 consecutive days between Visit 1 and Visit 2 (screening period).&#xD;
&#xD;
          4. Patients with a recent history (ie six months or less) of Acute Coronary Syndrome&#xD;
             (STEMI, non-STEMI, Unstable Angina Pectoris) prior to Visit 1 (screening).&#xD;
&#xD;
          5. Patients who have been hospitalised for cardiac failure during the past year prior to&#xD;
             Visit 1 (screening).&#xD;
&#xD;
          6. Patients with any unstable or life-threatening cardiac arrhythmia or cardiac&#xD;
             arrhythmia requiring intervention or a change in drug therapy within the past year&#xD;
             prior to Visit 1 (screening).&#xD;
&#xD;
          7. Patients with lung diseases other than asthma (eg COPD).&#xD;
&#xD;
          8. Patients with known active tuberculosis.&#xD;
&#xD;
          9. Patients with malignancy for which the patient has undergone resection, radiation&#xD;
             therapy or chemotherapy within the last five years prior to Visit 1 (screening).&#xD;
             Patients with treated basal cell carcinoma are allowed.&#xD;
&#xD;
         10. Patients who have undergone thoracotomy with pulmonary resection. Patients with a&#xD;
             history of thoracotomy for other reasons should be evaluated as per exclusion&#xD;
             criterion no. 1.&#xD;
&#xD;
         11. Patients with significant alcohol or drug abuse on Investigator's assessment within&#xD;
             the past two years prior to Visit 1 (screening).&#xD;
&#xD;
         12. Patients who are currently in a pulmonary rehabilitation program or have completed a&#xD;
             pulmonary rehabilitation program in the 6 weeks prior to Visit 1 (screening).&#xD;
&#xD;
         13. Patients with known hypersensitivity to anticholinergic drugs, BAC, EDTA or any other&#xD;
             components of the study medication delivery systems.&#xD;
&#xD;
         14. Pregnant or nursing women, including female patients with positive ß-HCG test at Visit&#xD;
             1.&#xD;
&#xD;
         15. Female patients of child-bearing potential not using highly effective method of birth&#xD;
             control. As defined in ICH (M3) [R09-1400], note 3, highly effective methods of birth&#xD;
             control are defined as those, alone or in combination, that result in a low failure&#xD;
             rate (ie less than 1% per year) when used consistently and correctly, such as&#xD;
             implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs),&#xD;
             sexual abstinence or vasectomised partner. Barrier contraceptives (eg male condom or&#xD;
             diaphragm) are acceptable if used in combination with spermicides (eg foam, gel).&#xD;
&#xD;
             Female patients will be considered to be of childbearing potential unless surgically&#xD;
             sterilised by hysterectomy or bilateral tubal ligation/salpingectomy, or&#xD;
             post-menopausal for at least two years.&#xD;
&#xD;
         16. Patients who have been treated with restricted medication prior to Visit 1 and/or&#xD;
             during the screening period.&#xD;
&#xD;
         17. Patients with any asthma exacerbation or any respiratory tract infection in the four&#xD;
             weeks prior to Visit 1 or during the screening period.&#xD;
&#xD;
             Visit 1 and/or Visit 2 should be postponed in case of an asthma exacerbation or&#xD;
             respiratory tract infection. Refer to Section 6.1 for information on re-scheduling of&#xD;
             visits.&#xD;
&#xD;
         18. Patients who are currently participating in another trial or who have been&#xD;
             participating in another trial within one month prior to Visit 0, and patients who&#xD;
             have previously been randomised in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</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>205.441.43004 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Grieskirchen</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.43003 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Linz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.43001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Thalheim bei Wels</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.43002 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Wels</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49015 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49003 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49014 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Frankfurt</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49007 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Großhansdorf</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49005 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49004 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Leipzig</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49010 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Lübeck</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49013 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Mannheim</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Neu-Isenburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49002 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Wiesbaden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.49011 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Wiesloch</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.36003 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Cegled</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.36002 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Godollo</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.36001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Pecs</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.36005 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Szazhalombatta</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.36004 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Szigetszentmiklos</city>
        <country>Hungary</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.38601 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Golnik</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.441.38602 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Kamnik</city>
        <country>Slovenia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Slovenia</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.441_c02103425-02.pdf</url>
    <description>Related Info</description>
  </link>
  <verification_date>July 2014</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>June 18, 2014</results_first_submitted>
  <results_first_submitted_qc>July 24, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">August 13, 2014</results_first_posted>
  <last_update_submitted>July 24, 2014</last_update_submitted>
  <last_update_submitted_qc>July 24, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 13, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tiotropium Bromide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Tio R2.5 Twice Daily (BID) / Tio R5 Once Daily (QD)</title>
          <description>Subjects were randomised to receive treatment with 2.5 μg tiotropium inhalation solution twice daily (i.e. in the morning and in the evening) and 5 μg tiotropium inhalation solution once daily in the evening via Respimat inhaler in a crossover manner using a predefined randomisation sequence.&#xD;
Treatment 1: Tio 2.5 µg BID (twice daily):Oral inhalation via the( Tiotropium-Respimat) inhaler of 2.5 µg twice daily i.e 2 actuations of 1.25 µg tiotropium in the morning and in the evening (total daily dose of 5 μg) Treatment 2: Tio 5 µg QD (once daily):Oral inhalation via the( Tiotropium-Respimat) inhaler of 5 µg once daily i.e 2 actuations of 2.5 µg tiotropium in the evening and 2 actuations of placebo in the morning (total daily dose of 5 μg)</description>
        </group>
        <group group_id="P2">
          <title>Tio R5 QD / Tio R2.5 BID</title>
          <description>Subjects were randomised to receive treatment with 2.5 μg tiotropium inhalation solution twice daily (i.e. in the morning and in the evening) and 5 μg tiotropium inhalation solution once daily in the evening via Respimat inhaler in a crossover manner using a predefined randomisation sequence.&#xD;
Treatment 1: Tio 5 µg QD (once daily):Oral inhalation via the( Tiotropium-Respimat) inhaler of 5 µg once daily i.e 2 actuations of 2.5 µg tiotropium in the evening and 2 actuations of placebo in the morning (total daily dose of 5 μg) Treatment 2: Tio 2.5 µg BID (twice daily):Oral inhalation via the( Tiotropium-Respimat) inhaler of 2.5 µg twice daily i.e 2 actuations of 1.25 µg tiotropium in the morning and in the evening (total daily dose of 5 μg)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Treatment Period 1: 4 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
        <period>
          <title>Treatment Period 2: 4 Weeks</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="50"/>
                <participants group_id="P2" count="47"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <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_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS) : All patients who were dispensed study medication and were documented as having taken at least one dose of investigational treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Baseline Total</title>
          <description>Total number of patients randomised and treated in the study.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="98"/>
          </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="43.8" spread="12.1"/>
                  </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="44"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 - 24h (AUC 0-24) Response.</title>
        <description>Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
        <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with inhaled corticosteroid (iCS).</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 - 24h (AUC 0-24) Response.</title>
          <description>Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Liters</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.219" spread="0.031"/>
                    <measurement group_id="O2" value="0.217" spread="0.031"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.002</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.018</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.038</ci_lower_limit>
            <ci_upper_limit>0.034</ci_upper_limit>
            <estimate_desc>Tio R5 QD - Tio R2.5 BID</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FEV1 AUC0-12h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
        <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 AUC0-12h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.182" spread="0.031" lower_limit="-0.032" upper_limit="0.052"/>
                    <measurement group_id="O2" value="0.192" spread="0.031" lower_limit="-0.032" upper_limit="0.052"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.010</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.021</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.032</ci_lower_limit>
            <ci_upper_limit>0.052</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FEV1 AUC12-24h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
        <time_frame>Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 AUC12-24h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.256" spread="0.033"/>
                    <measurement group_id="O2" value="0.243" spread="0.033"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.014</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.018</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.050</ci_lower_limit>
            <ci_upper_limit>0.022</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak FEV1 Response.</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FEV1 was defined as the highest FEV1 reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FEV1 Peak0-24h). The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
        <time_frame>10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks.</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak FEV1 Response.</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FEV1 was defined as the highest FEV1 reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FEV1 Peak0-24h). The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.465" spread="0.031"/>
                    <measurement group_id="O2" value="0.451" spread="0.031"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.014</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.018</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.051</ci_lower_limit>
            <ci_upper_limit>0.023</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough FEV1 (L) Response.</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FEV1 was defined as the FEV1 value just prior to the last evening dose of study medication.</description>
        <time_frame>10 minutes (min) prior to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Trough FEV1 (L) Response.</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FEV1 was defined as the FEV1 value just prior to the last evening dose of study medication.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.203" spread="0.033"/>
                    <measurement group_id="O2" value="0.207" spread="0.034"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.004</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.032</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.060</ci_lower_limit>
            <ci_upper_limit>0.068</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Forced Vital Capacity (FVC) AUC0-24h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Vital Capacity (FVC) AUC0-24h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.&#xD;
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.079" spread="0.032"/>
                    <measurement group_id="O2" value="0.075" spread="0.032"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested.</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.005</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.020</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.044</ci_lower_limit>
            <ci_upper_limit>0.035</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FVC AUC0-12h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>FVC AUC0-12h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.056" spread="0.031"/>
                    <measurement group_id="O2" value="0.053" spread="0.031"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.003</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.023</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.048</ci_lower_limit>
            <ci_upper_limit>0.042</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FVC AUC12-24h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>FVC AUC12-24h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.102" spread="0.034"/>
                    <measurement group_id="O2" value="0.096" spread="0.034"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.006</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.020</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.047</ci_lower_limit>
            <ci_upper_limit>0.034</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak FVC Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FVC was defined as the highest FVC reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FVC Peak0-24h).</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak FVC Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FVC was defined as the highest FVC reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FVC Peak0-24h).</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.328" spread="0.033"/>
                    <measurement group_id="O2" value="0.309" spread="0.033"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-0.019</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.026</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.070</ci_lower_limit>
            <ci_upper_limit>0.032</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough FVC Responses</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FVC was defined as the FVC value just prior to the last evening dose of study medication.</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Trough FVC Responses</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FVC was defined as the FVC value just prior to the last evening dose of study medication.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.077" spread="0.034"/>
                    <measurement group_id="O2" value="0.118" spread="0.034"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.041</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.035</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-0.030</ci_lower_limit>
            <ci_upper_limit>0.111</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak Expiratory Flow (PEF) AUC0-24h Response</title>
        <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres per minute.</description>
        <time_frame>Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks</time_frame>
        <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
        <group_list>
          <group group_id="O1">
            <title>Tio R2.5 BID</title>
            <description>Tiotropium 2.5 mcg BID morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
          <group group_id="O2">
            <title>Tio R5 QD</title>
            <description>Tiotropium 5 mcg QD in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak Expiratory Flow (PEF) AUC0-24h Response</title>
          <description>MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres per minute.</description>
          <population>Full Analysis Set (FAS): The full analysis set (FAS) includes all patients in the treated set who had baseline data and at least one on-treatment efficacy value after 4 weeks on treatment within a period.</population>
          <units>Litres/min</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="98"/>
                <count group_id="O2" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.788" spread="5.923"/>
                    <measurement group_id="O2" value="41.399" spread="5.933"/>
                  </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>No p-values are presented as no formal statistical hypothesis was tested</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.389</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>3.658</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_lower_limit>-8.651</ci_lower_limit>
            <ci_upper_limit>5.873</ci_upper_limit>
            <estimate_desc>Tio R5 qd - Tio R2.5 bid</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline visit to end of study drug administration, plus 30 days, up to 82 days.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Tio R2.5 Bid</title>
          <description>Tiotropium 2.5 mcg bid morning and evening delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
        </group>
        <group group_id="E2">
          <title>Tio R5 qd</title>
          <description>Tiotropium 5 mcg qd in the evening and matching placebo qd in the morning delivered by the Respimat inhaler, on top of maintenance therapy with iCS.</description>
        </group>
      </group_list>
      <serious_events>
        <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, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cervix carcinoma stage 0</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical dysplasia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
              </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 Pharmaceuticals</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/NCT01696071
org study id: 205.441
secondary id: 2012-001873-10
nct id: NCT01696071
lead sponsor: 
collaborator: 
Determine the 24-hour FEV1-profile of tiotropium solution for inhalation after 4 weeks
      treatment periods of 5 mcg tiotropium administered once daily in the evening and 2.5 mcg
      tiotropium administered twice daily (morning and evening). In addition compare the 24 hours
      pharmacokinetic profile of 5 mcg tiotropium administered once daily and 2.5mcg tiotropium
      administered twice daily in pharmacokinetic sub-investigation.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 - 24h (AUC 0-24) Response.
time frame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: Mixed Model Repeated Measure (MMRM) results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.
measure: FEV1 AUC0-12h Response
time frame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
measure: FEV1 AUC12-24h Response
time frame: Baseline FEV1 taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
measure: Peak FEV1 Response.
time frame: 10 minutes (min) prior to dose to 30 min,1 hour (h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks.
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FEV1 was defined as the highest FEV1 reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FEV1 Peak0-24h). The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.
measure: Trough FEV1 (L) Response.
time frame: 10 minutes (min) prior to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FEV1 was defined as the FEV1 value just prior to the last evening dose of study medication.
measure: Forced Vital Capacity (FVC) AUC0-24h Response
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres.
The values recorded at 11 hours 50 minutes and at 23 hours 50 minutes post dosing were assigned to 12 and 24 hours, respectively.
measure: FVC AUC0-12h Response
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline. Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-12h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
measure: FVC AUC12-24h Response
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC12 -24h calculated using the trapezoidal rule divided by the observation time (12 hours) to report in litres.
measure: Peak FVC Response
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Peak FVC was defined as the highest FVC reading observed within the 24 hour period following inhalation of the last evening dose of study medication (FVC Peak0-24h).
measure: Trough FVC Responses
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. Trough FVC was defined as the FVC value just prior to the last evening dose of study medication.
measure: Peak Expiratory Flow (PEF) AUC0-24h Response
time frame: Baseline taken at visit 2 prior to the first evening dose of randomised study medication. Then, 10 minutes(min) prior to dose to 30min,1hour(h),2h,3h,4h,11h50min,12h30min,13h,14h,15h,16h,18h,20h,22h and 23h,23h50min relative to dose after 4 weeks
description: MMRM results. Response was defined as change from baseline. Means are adjusted for treatment, period, patient and study baseline.Measured following the respective dosing determined at the end of each 4 week period of randomised treatment. AUC0-24h calculated using the trapezoidal rule divided by the observation time (24 hours) to report in litres per minute.
arm group label: Treatment A
arm group type: Experimental
description: 2 puffs of daily dose (5 mcg) in the evening and 2 puffs of matching placebo in the morning via Respimat inhaler
arm group label: Treatment B
arm group type: Experimental
description: 2 puffs of half daily dose (2.5 mcg) twice daily, in the evening and in the morning via Respimat inhaler
intervention type: Drug
intervention name: Tiotropium 5 mcg qd
description: 2 puffs (2.5 mcg each) in the evening 5 mcg in total and 2 puffs of matching placebo in the morning
arm group label: Treatment A
intervention type: Drug
intervention name: Tiotropium 2.5 mcg bid
description: 2 puffs (1.25 mcg each) twice daily, in the evening and in the morning, 5 mcg in total
arm group label: Treatment B
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Austria
country: Germany
country: Hungary
country: Slovenia
url: http://trials.boehringer-ingelheim.com/content/dam/internet/opu/clinicaltrial/com_EN/results/205/205.441_c02103425-02.pdf
description: Related Info
responsible party type: Sponsor
mesh term: Asthma
mesh term: Tiotropium Bromide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 