<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/NCT01662986</url>
  </required_header>
  <id_info>
    <org_study_id>205.478</org_study_id>
    <nct_id>NCT01662986</nct_id>
  </id_info>
  <brief_title>Investigate the Impact of Early Treatment Initiation With Tiotropium in Patients Recovering From Hospitalization for an Acute COPD Exacerbation 2</brief_title>
  <official_title>A Randomized, Placebo-controlled, Double-blind, Parallel Group, Multi Center Study to Assess the Safety and Efficacy of Tiotropium Bromide (18 µg) Delivered Via the HandiHaler® in Chronic Obstructive Pulmonary Disease (COPD) Subjects Recovering From Hospitalization for an Acute Exacerbation (Hospital Discharge Study 2)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      A randomized, placebo-controlled, double-blind, parallel group, multi-center study to assess&#xD;
      the safety and efficacy of tiotropium bromide (18 µg) delivered via the HandiHaler® in&#xD;
      Chronic Obstructive Pulmonary Disease (COPD) subjects recovering from hospitalization for an&#xD;
      acute exacerbation (Hospital Discharge Study 2)&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2012</start_date>
  <completion_date type="Actual">April 1, 2014</completion_date>
  <primary_completion_date type="Actual">April 1, 2014</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug.</measure>
    <time_frame>Baseline and 12 weeks</time_frame>
    <description>Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.&#xD;
Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed.&#xD;
This endpoint was analysed using combined data, as specified in the analysis plan</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Trough FVC at 12 Weeks on Study Drug.</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With Adverse Clinical Event During on Study.</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>Baseline and week 12</time_frame>
    <description>Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>Baseline and week 12</time_frame>
    <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study.&#xD;
A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following:&#xD;
1) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness.&#xD;
Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment.&#xD;
A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study.&#xD;
All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures.&#xD;
Hospitalizations occurring on the same day as discharge were not considered a separate admission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>from date of hospital discharge prior to randomization upto readmission days &gt;1 and &lt;31 days</time_frame>
    <description>Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed.&#xD;
Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1.&#xD;
The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days &gt;1 and &lt;31 days using the TS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years</time_frame>
    <description>Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years</time_frame>
    <description>Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
    <description>Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</measure>
    <time_frame>from first drug administration to the last timepoint with information of EXACT-PRO, Up to 2 years</time_frame>
    <description>Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported.&#xD;
Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average.&#xD;
Analysis based on Kaplan Meier estimate</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>18 mcg tiotropium bromide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patient to receive one tiotropium bromide inhalation powder capsule daily (in the morning) via HandiHaler</description>
  </arm_group>
  <arm_group>
    <arm_group_label>placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Patient to receive one placebo inhalation powder capsule daily (in the morning) via HandiHaler</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>tiotropium bromide</intervention_name>
    <description>18 mcg once a day (QD)</description>
    <arm_group_label>18 mcg tiotropium bromide</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Once a day (QD)</description>
    <arm_group_label>placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
        The following inclusion criteria apply at Visit 0:&#xD;
&#xD;
          1. All subjects must sign an informed consent consistent with the International&#xD;
             Conference on Harmonization - Good Clinical Practice (ICH-GCP) guidelines prior to&#xD;
             participation in the trial and conducting any study procedures&#xD;
&#xD;
          2. Male or female subjects 40 years of age or older.&#xD;
&#xD;
          3. Hospitalization for a primary diagnosis of acute COPD exacerbation for =14 days.&#xD;
             Determination of accuracy of admission diagnosis will be at the discretion of the&#xD;
             investigator.&#xD;
&#xD;
          4. Patient reported hospital length of stay and discharge date (confirmed with hospital&#xD;
             discharge summary/hospital records; however, medical record confirmation may occur&#xD;
             following randomization).&#xD;
&#xD;
             The following inclusion criteria apply at Visit 1:&#xD;
&#xD;
          5. Discharged from the hospital =10 days from date of randomization.&#xD;
&#xD;
          6. All subjects must have a diagnosis of COPD (P12-01205), and have documented airway&#xD;
             obstruction with a post-bronchodilator Force Expiratory Volume in 1 second (FEV1)\&#xD;
             Force vital capacity (FVC) &lt;0.7(See Section 5.1.2, Pulmonary Function Testing). The&#xD;
             diagnosis of COPD can be made at Visit 1 if no Pulmonary Function Testing (PFT) data&#xD;
             available within the past 12 months.&#xD;
&#xD;
          7. Subjects must be current or ex-smoker with a smoking history of =10 pack-years:&#xD;
&#xD;
        Pack-years = Number of cigarettes/day x years of smoking 20 cigarettes/ pack 8. Subjects&#xD;
        must be able to inhale medication in a competent manner from the HandiHaler® device&#xD;
        (Appendix 10.1) and from a metered dose inhaler (MDI).&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
        The following exclusion criterion applies at Visit 0:&#xD;
&#xD;
          1. No more than 30 days of therapy with any long-acting inhaled anticholinergic over&#xD;
             preceding 3 months prior to discharge from the hospital, and no therapy with any long&#xD;
             acting anticholinergic post discharge (no use between hospital discharge and&#xD;
             randomization) or any other restricted concomitant medications&#xD;
&#xD;
             The following exclusion criteria apply at Visit 1:&#xD;
&#xD;
          2. Presence of a significant disease (in the opinion of the investigator) which may put&#xD;
             the subject at risk because of participation in the study or may influence the&#xD;
             subject's ability to participate in the study for up to 2 years.&#xD;
&#xD;
          3. A documented history of myocardial infarction during the hospitalization preceding&#xD;
             randomization. Subjects being stable with a history of cardiac stents are permitted.&#xD;
&#xD;
          4. Any unstable or life-threatening cardiac arrhythmia requiring intervention or change&#xD;
             in drug therapy during the last year.&#xD;
&#xD;
          5. Subjects with asthma (subject treated for asthma in the last 2 years, history of&#xD;
             childhood asthma is permitted), cystic fibrosis, clinical diagnosis of bronchiectasis,&#xD;
             interstitial lung disease, pulmonary thromboembolic disease or known active&#xD;
             tuberculosis.&#xD;
&#xD;
        7. Malignancy for which the subject has undergone resection, radiation, chemotherapy or&#xD;
        biological treatments within the last two years or is currently on active radiation&#xD;
        therapy, chemotherapy or biological treatment. Subjects with treated basal cell carcinoma&#xD;
        and non-invasive squamous cell skin carcinoma are allowed.&#xD;
&#xD;
        8. Hospitalization for cardiac failure (New York Heart Association (NYHA) class III or IV)&#xD;
        during the hospitalization preceding randomization.&#xD;
&#xD;
        9. Known hypersensitivity to anticholinergic drugs, lactose, or any other components of the&#xD;
        HandiHaler® or MDI inhalation solution delivery system.&#xD;
&#xD;
        10. Known moderate to severe renal impairment as judged by the investigator. 11. Known&#xD;
        narrow angle glaucoma as judged by the investigator. 12. Significant symptomatic prostatic&#xD;
        hyperplasia or bladder-neck obstruction. Subjects whose symptoms are controlled on&#xD;
        treatment may be included.&#xD;
&#xD;
        13. Pregnant or nursing women or women of childbearing potential not using a medically&#xD;
        approved means of contraception (i.e., oral contraceptives, intrauterine devices, diaphragm&#xD;
        or sub dermal implants e.g., Norplant®) for at least three months prior to and for the&#xD;
        duration of the trial.&#xD;
&#xD;
        14. Significant alcohol or drug abuse within the past 12 months. 15. Previously randomized&#xD;
        in this study or currently participating in another interventional study.&#xD;
&#xD;
        16. Visual impairment that as judged by the investigator does not allow the subject to&#xD;
        independently read and complete the questionnaires and eDiary.&#xD;
&#xD;
        17. Any significant or new ECG findings at Visit 1 as judged by the investigator,&#xD;
        including, but not limited to signs of acute ischemia, arrhythmia.&#xD;
&#xD;
        18. Treatment with any restricted pulmonary medication. 19. Residing in an assisted living&#xD;
        facility.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>205.478.00243 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00208 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Flagstaff</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00260 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00241 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Loma Linda</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00240 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00237 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00231 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00209 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Danbury</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00250 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Glastonbury</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00229 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00200 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00212 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00265 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Kissimmee</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00246 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Lehigh Acres</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00248 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00215 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00261 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00233 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Vero Beach</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00236 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Austell</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00205 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Lawrenceville</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00225 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Evanston</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00264 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00254 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Olathe</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00249 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Topeka</city>
        <state>Kansas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00257 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hazard</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00234 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00242 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00258 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Eunice</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00256 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00210 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00220 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Towson</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00204 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>North Dartmouth</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00247 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Winston Salem</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00263 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00201 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00239 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00227 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Summit</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00253 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00226 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00232 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00203 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00206 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Wyomissing</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00219 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00222 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00235 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Kingwood</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00217 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>McKinney</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00216 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Temple</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00230 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Falls Church</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00202 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>205.478.00224 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Puerto Rico</country>
  </removed_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>September 2018</verification_date>
  <study_first_submitted>August 9, 2012</study_first_submitted>
  <study_first_submitted_qc>August 9, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>April 24, 2015</results_first_submitted>
  <results_first_submitted_qc>July 17, 2015</results_first_submitted_qc>
  <results_first_posted type="Estimate">July 20, 2015</results_first_posted>
  <last_update_submitted>September 21, 2018</last_update_submitted>
  <last_update_submitted_qc>September 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 17, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bromides</mesh_term>
    <mesh_term>Tiotropium Bromide</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Randomized, placebo-controlled, double blind, parallel group design involving an event-driven treatment period up to the close of the study and a minimum 30-day follow-up period up to the close of the study</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
        </group>
        <group group_id="P2">
          <title>Tiotropium Bromide (18 μg)</title>
          <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="40"/>
                <participants group_id="P2" count="39"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="22"/>
                <participants group_id="P2" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="13"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Not Treated</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other than stated above</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <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): The treated set included all patients randomized and who took at least one dose of the study drug.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
        </group>
        <group group_id="B2">
          <title>Tiotropium Bromide (18 μg)</title>
          <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="39"/>
            <count group_id="B2" value="39"/>
            <count group_id="B3" value="78"/>
          </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="60.0" spread="8.6"/>
                    <measurement group_id="B2" value="58.4" spread="7.0"/>
                    <measurement group_id="B3" value="59.2" spread="7.8"/>
                  </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="19"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug.</title>
        <description>Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
        <time_frame>Baseline and 12 weeks</time_frame>
        <population>Treated Set (TS): The treated set included all patients randomized and who took at least one dose of the study drug. The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug.</title>
          <description>Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
          <population>Treated Set (TS): The treated set included all patients randomized and who took at least one dose of the study drug. The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.124" spread="0.271"/>
                    <measurement group_id="O2" value="0.186" spread="0.475"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Trough FVC at 12 Weeks on Study Drug.</title>
        <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Treated Set (TS). The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Trough FVC at 12 Weeks on Study Drug.</title>
          <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
          <population>Treated Set (TS). The number of patients analyzed at week 12 from the treated set were 29 for Placebo and 30 for Tiotropium.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="29"/>
                <count group_id="O2" value="30"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.090" spread="0.399"/>
                    <measurement group_id="O2" value="0.282" spread="0.558"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With Adverse Clinical Event During on Study.</title>
        <description>Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set (TS)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Adverse Clinical Event During on Study.</title>
          <description>Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.</description>
          <population>Treated Set (TS)</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="39"/>
                <count group_id="O2" value="39"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.9"/>
                    <measurement group_id="O2" value="46.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
        <time_frame>Baseline and week 12</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug.&#xD;
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.035" spread="0.262"/>
                    <measurement group_id="O2" value="0.185" spread="0.384"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
        <time_frame>Baseline and week 12</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed at week 12 from the treated set were 59 for Placebo and 60 for Tiotropium.</population>
          <units>Litres</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="59"/>
                <count group_id="O2" value="60"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.015" spread="0.396"/>
                    <measurement group_id="O2" value="0.278" spread="0.447"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study.&#xD;
A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following:&#xD;
1) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness.&#xD;
Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment.&#xD;
A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors).</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study.&#xD;
A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following:&#xD;
1) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness.&#xD;
Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment.&#xD;
A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors).</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.9"/>
                    <measurement group_id="O2" value="40.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</title>
        <description>Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study.&#xD;
All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures.&#xD;
Hospitalizations occurring on the same day as discharge were not considered a separate admission.</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</title>
          <description>Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study.&#xD;
All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures.&#xD;
Hospitalizations occurring on the same day as discharge were not considered a separate admission.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.9"/>
                    <measurement group_id="O2" value="26.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed.&#xD;
Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1.&#xD;
The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days &gt;1 and &lt;31 days using the TS.</description>
        <time_frame>from date of hospital discharge prior to randomization upto readmission days &gt;1 and &lt;31 days</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed.&#xD;
Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1.&#xD;
The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days &gt;1 and &lt;31 days using the TS.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.1"/>
                    <measurement group_id="O2" value="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
        <time_frame>start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.</population>
          <units>exacerbations per patient year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3"/>
                    <measurement group_id="O2" value="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
        <time_frame>start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 73 for Placebo and 54 for Tiotropium.</population>
          <units>Patient years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="73"/>
                <count group_id="O2" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.0"/>
                    <measurement group_id="O2" value="60.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</title>
        <description>Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.&#xD;
Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed.&#xD;
This endpoint was analysed using combined data, as specified in the analysis plan</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477 : This set includes all patients who were randomized and took at least one dose of the study drug, 157 patients (79 tiotropium and 78 placebo) were included in this set.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).</title>
          <description>Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.&#xD;
Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed.&#xD;
This endpoint was analysed using combined data, as specified in the analysis plan</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477 : This set includes all patients who were randomized and took at least one dose of the study drug, 157 patients (79 tiotropium and 78 placebo) were included in this set.</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="78"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.4"/>
                    <measurement group_id="O2" value="53.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.</population>
          <units>hospitalizations per patient year</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                    <measurement group_id="O2" value="0.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
        <time_frame>from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years</time_frame>
        <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.</description>
          <population>Treated Set of the pooled twin studies 205.478 and 205.477. The number of patients analyzed for this endpoint from the treated set were 47 for Placebo and 38 for Tiotropium.</population>
          <units>patient years</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="47"/>
                <count group_id="O2" value="38"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="58.0"/>
                    <measurement group_id="O2" value="60.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
        <description>Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported.&#xD;
Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average.&#xD;
Analysis based on Kaplan Meier estimate</description>
        <time_frame>from first drug administration to the last timepoint with information of EXACT-PRO, Up to 2 years</time_frame>
        <population>Patients who had baseline and post-baseline measurements of EXACT-PRO.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Patient to receive oral inhalation of one placebo powder capsule once daily in the morning via HandiHaler.</description>
          </group>
          <group group_id="O2">
            <title>Tiotropium Bromide (18 μg)</title>
            <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)</title>
          <description>Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported.&#xD;
Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average.&#xD;
Analysis based on Kaplan Meier estimate</description>
          <population>Patients who had baseline and post-baseline measurements of EXACT-PRO.</population>
          <units>Percentage of patients recovered</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="76"/>
                <count group_id="O2" value="76"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="94.0"/>
                    <measurement group_id="O2" value="88.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first drug administration until 30 days after the last drug administration, up to 405 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Patient to receive one placebo inhalation powder capsule once daily in the morning via HandiHaler</description>
        </group>
        <group group_id="E2">
          <title>Tiotropium Bromide (18 μg)</title>
          <description>Patient to receive oral inhalation of one tiotropium bromide powder capsule once daily in the morning via HandiHaler</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 17.0</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="9" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Melaena</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Upper gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Bile duct stone</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cholangitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cholecystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection viral</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Femur fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Confusional state</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Substance abuse</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Hydronephrosis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 17.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="11" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="23" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest discomfort</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Candida infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Oral candidiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Contusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="39"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="39"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>Boehringer Ingelheim (BI) acknowledges that investigators have the right to publish the study results. Investigators shall provide BI with a copy of any publication or presentation for review prior to any submission. Such review will be done with regard to proprietary information, information related to patentable inventions, medical, scientific, and statistical accuracy within 60 days. BI may request a delay of the publication in order to protect BI's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The original protocol planned to randomize 604 subjects. However this was not reached due to low patient enrollment.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Boehringer Ingelheim Call Center</name_or_title>
      <organization>Boehringer Ingelheim</organization>
      <phone>1-800-243-0127</phone>
      <email>clintriage.rdg@boehringer-ingelheim.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01662986
org study id: 205.478
nct id: NCT01662986
lead sponsor: 
A randomized, placebo-controlled, double-blind, parallel group, multi-center study to assess
      the safety and efficacy of tiotropium bromide (18 µg) delivered via the HandiHaler® in
      Chronic Obstructive Pulmonary Disease (COPD) subjects recovering from hospitalization for an
      acute exacerbation (Hospital Discharge Study 2)
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug.
time frame: Baseline and 12 weeks
description: Change from baseline of trough forced expiratory volume in 1 second (FEV1) at 12 weeks on study drug.
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.
measure: Percentage of Patients With Next Adverse Clinical Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Percentage (number) of patients with next adverse clinical outcome event occured during the study, defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.
Time to the next adverse clinical outcome event from the Two Twin Trials, present 205.478 (NCT01662986) and 205.477 (NCT01663987) was not analysed, only Kaplan Meier curve was plotted. So this endpoint has not been disclosed.
This endpoint was analysed using combined data, as specified in the analysis plan
measure: Change From Baseline of Trough FVC at 12 Weeks on Study Drug.
time frame: baseline and 12 weeks
description: Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
measure: Percentage of Patients With Adverse Clinical Event During on Study.
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Percentage (number) of patients with adverse clinical event on study, which is defined as the combined endpoint of Chronic obstructive pulmonary disease (COPD) exacerbations per Boehringer Ingelheim (BI) definition, all-cause re-hospitalization, or all-cause mortality.
measure: Change From Baseline of Trough FEV1 at 12 Weeks on Study Drug From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: Baseline and week 12
description: Change from baseline of trough FEV1 (forced expiratory volume in 1 second) at 12 weeks on study drug.
Trough FEV1 is defined as the FEV1 measurement prior to the next dosing of study drug and approximately 24 hours after last inhalation of drug.
measure: Change From Baseline of Trough FVC at 12 Weeks From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: Baseline and week 12
description: Change from baseline of trough Forced Vital Capacity (FVC) at 12 weeks on study drug.
measure: Percentage of Patients With COPD Exacerbation From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Percentage (number) of patients with COPD exacerbation on study was analysed for the combined study.
A COPD exacerbation was defined as a complex of lower respiratory events/symptoms (increase or new onset) related to the underlying COPD with duration of three days or more, requiring a change in treatment where a complex of lower respiratory events/symptoms was defined as at least two of the following:
1) Shortness of breath; 2) Sputum production (volume) ; 3) Occurrence of purulent sputum; 4) Cough; 5) Wheezing; 6) Chest tightness.
Onset of exacerbation was defined by the onset of first recorded symptom.The end of exacerbation was decided by the investigator based on clinical judgment.
A required change in treatment included either prescription of antibiotics and/or systemic steroids; and/or a newly prescribed maintenance respiratory medication (i.e., bronchodilators including theophyllines and PDE4-inhibitors).
measure: Percentage of Patients With All-cause Hospitalization From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987).
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Percentage (number) of patients with all-cause hospitalization outcome event occured during the study was analysed for the combined study.
All-cause hospitalization included all hospitalizations, except planned hospitalizations for elective procedures.
Hospitalizations occurring on the same day as discharge were not considered a separate admission.
measure: Percentage of Patients With 30-day Hospital Readmission Rates Outcome Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: from date of hospital discharge prior to randomization upto readmission days >1 and <31 days
description: Percentage (number) of patients with 30-day hospital readmission rates outcome events was analysed.
Days to hospital readmission were calculated as:Hospital readmission days = Readmission date - Date of hospital discharge + 1.
The 30-day hospital readmission analysis summarized the frequency of patients with hospital readmission and readmission days >1 and <31 days using the TS.
measure: Number of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years
description: Number of COPD exacerbation per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
measure: Exposure of COPD Exacerbation Events From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: start of treatment to the last timepoint with information of clinical adverse outcome available,Up to 2 years
description: Total patient year exposure of COPD was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.
measure: Number of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Number of all-cause hospitalization per patient year outcome event occured during the study was analysed descriptively by calculating average occurrence (number of events per patient year drug exposure) by treatment group for on study period using the TS.
measure: Exposure of All-cause Hospitalization Event From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: from first drug administration to the last timepoint with information of clinical adverse outcome available, Up to 2 years
description: Total patient year exposure of all-cause hospitalization was calculated by aggregating the time to min(treatment stop +30, last contact) for on-treatment analysis, or time to last contact for on-study analysis.
measure: Time to Event: Time to Recovery (EXACT-PRO) From the Two Twin Trials, Present 205.478 (NCT01662986) and 205.477 (NCT01663987)
time frame: from first drug administration to the last timepoint with information of EXACT-PRO, Up to 2 years
description: Time to event: Time to recovery based on EXACT-PRO total score. The percentage of observed patients recovered by end of study was reported.
Time to recovery was assessed with the EXACT-PRO questionnaire. EXACT-PRO total scores were transformed to smooth scores for determining time to recovery and all other endpoints related to the EXACT questionnaire. The day-2 score was transformed to the mean of the total scores recorded on Day 1, 2, and 3. Similarly, each subsequent day's score was transformed to the mean score using a rolling 3-day average.
Analysis based on Kaplan Meier estimate
arm group label: 18 mcg tiotropium bromide
arm group type: Active Comparator
description: Patient to receive one tiotropium bromide inhalation powder capsule daily (in the morning) via HandiHaler
arm group label: placebo
arm group type: Placebo Comparator
description: Patient to receive one placebo inhalation powder capsule daily (in the morning) via HandiHaler
intervention type: Drug
intervention name: tiotropium bromide
description: 18 mcg once a day (QD)
arm group label: 18 mcg tiotropium bromide
intervention type: Drug
intervention name: Placebo
description: Once a day (QD)
arm group label: placebo
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
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country: United States
country: Puerto Rico
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Bromides
mesh term: Tiotropium Bromide
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The original protocol planned to randomize 604 subjects. However this was not reached due to low patient enrollment.
point of contact: 