<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/NCT01696058</url>
  </required_header>
  <id_info>
    <org_study_id>1222.52</org_study_id>
    <nct_id>NCT01696058</nct_id>
  </id_info>
  <brief_title>Co-administration of Olodaterol Respimat® and Tiotropium Handihaler®</brief_title>
  <official_title>A Randomised, Double Blind, Parallel Group Study to Assess the Efficacy and Safety of 12 Weeks of Once Daily, Orally Inhaled, Co-administration of Olodaterol 5µg (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) Compared to Once Daily, Orally Inhaled, Co-administration of Placebo (Delivered by the Respimat® Inhaler) and Tiotropium 18µg (Delivered by the HandiHaler®) in Patients With Chronic Obstructive Pulmonary Disease (COPD)[ANHELTO TM 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>
      The overall objective of this study is to assess efficacy and safety of 12 weeks, once daily,&#xD;
      orally inhaled co-administration of olodaterol 5 µg (delivered by the Respimat® Inhaler) and&#xD;
      tiotropium (delivered by the Handihaler® as Spiriva Handihaler®), compared to tiotropium&#xD;
      (Spiriva Handihaler®) monotherapy on lung function in patients with COPD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">October 2013</completion_date>
  <primary_completion_date type="Actual">October 2013</primary_completion_date>
  <phase>Phase 3</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>FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data</measure>
    <time_frame>12 weeks</time_frame>
    <description>The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores [dichotomous (true/false) except last question (4-point Likert scale)]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline</measure>
    <time_frame>baseline and 12 Weeks</time_frame>
    <description>Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak FVC Response at 12 Weeks; Defined as Change From Baseline</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Peak FVC response at 12 weeks - defined as change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough FVC Response at 12 Weeks; Defined as Change From Baseline</measure>
    <time_frame>baseline and 12 weeks</time_frame>
    <description>Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Usage - Percentage of Rescue Free Days</measure>
    <time_frame>over 12 weeks</time_frame>
    <description>Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment).&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)</measure>
    <time_frame>over 12 weeks</time_frame>
    <description>Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)</measure>
    <time_frame>over 12 weeks</time_frame>
    <description>Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)</measure>
    <time_frame>over 12 weeks</time_frame>
    <description>Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">1137</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Olodaterol andTiotropium</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo and Tiotropium</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>marketed product</description>
    <arm_group_label>Placebo and Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo matching Olodaterol</intervention_name>
    <description>one dose</description>
    <arm_group_label>Placebo and Tiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>marketed product</description>
    <arm_group_label>Olodaterol andTiotropium</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olodaterol</intervention_name>
    <description>one dose</description>
    <arm_group_label>Olodaterol andTiotropium</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          1. All patients must sign an informed consent consistent with International Conference on&#xD;
             Harmonization-Good Clinical Practice (ICH-GCP) guidelines prior to participation in&#xD;
             the trial, which includes medication washout and restrictions.&#xD;
&#xD;
          2. All patients must have a diagnosis of chronic obstructive pulmonary disease and must&#xD;
             meet the following spirometric criteria: Patients must have a relatively stable airway&#xD;
             obstruction with a post-bronchodilator FEV1 ≥ 30 % and &lt; 80% of predicted normal and a&#xD;
             post-bronchodilator FEV1/FVC &lt;70% at Visit 1.&#xD;
&#xD;
          3. Male or female patients, 40 years of age or older.&#xD;
&#xD;
          4. Patients must be current or ex-smokers with a smoking history of more than 10 pack&#xD;
             years&#xD;
&#xD;
          5. Patients must be able to: perform technically acceptable pulmonary function tests, and&#xD;
             maintain records(paper diary).&#xD;
&#xD;
          6. Patients must be able to inhale medication in a competent manner from the Respimat&#xD;
             Inhaler as well as the Handihaler.&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          1. Patients with a significant disease other than COPD; a significant disease is defined&#xD;
             as a disease which, in the opinion of the investigator, may (i) put the patient at&#xD;
             risk because of participation in the study, (ii) influence the results of the study,&#xD;
             or (iii) cause concern regarding the patients ability to participate in the study.&#xD;
&#xD;
          2. Patients with clinically relevant abnormal baseline haematology, blood chemistry, or&#xD;
             urinalysis; all patients with an AST &gt;x2 ULN, ALT &gt;x2 ULN, bilirubin &gt;x2 ULN or&#xD;
             creatinine &gt;x2 ULN will be excluded regardless of clinical condition (a repeat&#xD;
             laboratory evaluation will not be conducted in these patients).&#xD;
&#xD;
          3. Patients with a history of asthma. For patients with allergic rhinitis or atopy,&#xD;
             source documentation is required to verify that the patient does not have asthma. If a&#xD;
             patient has a total blood eosinophil count ≥600/mm3, source documentation is required&#xD;
             to verify that the increased eosinophil count is related to a non-asthmatic condition.&#xD;
&#xD;
          4. A diagnosis of thyrotoxicosis (due to the known class side effect profile of&#xD;
             ß2-agonists).&#xD;
&#xD;
          5. A diagnosis of paroxysmal tachycardia (&gt;100 beats per minute) (due to the known class&#xD;
             side effect profile of ß2-agonists).&#xD;
&#xD;
          6. A history of myocardial infarction within 1 year of screening visit (Visit 1).&#xD;
&#xD;
          7. Unstable or life-threatening cardiac arrhythmia.&#xD;
&#xD;
          8. Hospitalization for heart failure within the past year.&#xD;
&#xD;
          9. Known active tuberculosis.&#xD;
&#xD;
         10. A malignancy for which patient has undergone resection, radiation therapy or&#xD;
             chemotherapy within last five years (patients with treated basal cell carcinoma are&#xD;
             allowed).&#xD;
&#xD;
         11. A history of life-threatening pulmonary obstruction.&#xD;
&#xD;
         12. A history of cystic fibrosis.&#xD;
&#xD;
         13. Clinically evident bronchiectasis.&#xD;
&#xD;
         14. A history of significant alcohol or drug abuse.&#xD;
&#xD;
         15. Patients who have undergone thoracotomy with pulmonary resection (patients with a&#xD;
             history of thoracotomy for other reasons should be evaluated as per exclusion&#xD;
             criterion No. 1).&#xD;
&#xD;
         16. Patients being treated with oral or patch ß-adrenergics.&#xD;
&#xD;
         17. Patients being treated with oral corticosteroid medication at unstable doses (i.e.,&#xD;
             less than six weeks on a stable dose) or at doses in excess of the equivalent of 10 mg&#xD;
             of prednisone per day or 20 mg every other day.&#xD;
&#xD;
         18. Patients who regularly use daytime oxygen therapy for more than one hour per day and&#xD;
             in the investigators opinion will be unable to abstain from the use of oxygen therapy&#xD;
             during clinic visits.&#xD;
&#xD;
         19. Patients who have completed a pulmonary rehabilitation program in the six weeks prior&#xD;
             to the screening visit (Visit 1) or patients who are currently in a pulmonary&#xD;
             rehabilitation program.&#xD;
&#xD;
         20. Patients who have taken an investigational drug within one month or six half lives&#xD;
             (whichever is greater) prior to screening visit (Visit 1).&#xD;
&#xD;
         21. Patients with known hypersensitivity to ß-adrenergic drugs, BAC, EDTA, or any other&#xD;
             component of the Respimat® inhalation solution.&#xD;
&#xD;
         22. Patients with known hypersensitivity to anticholinergic drugs, lactose, or any other&#xD;
             components of the HandiHaler®.&#xD;
&#xD;
         23. Pregnant or nursing women.&#xD;
&#xD;
         24. Women of childbearing potential not using a highly effective method of birth control*.&#xD;
             Female patients will be considered to be of childbearing potential unless surgically&#xD;
             sterilised by hysterectomy or bilateral tubal ligation, or post-menopausal for at&#xD;
             least two years.&#xD;
&#xD;
             * as per ICH M3(R2) a highly effective method of birth control is defined as those&#xD;
             which result in a low failure rate (i.e. less than 1% per year).&#xD;
&#xD;
         25. Patients who have previously been randomised in this study or are currently&#xD;
             participating in another study.&#xD;
&#xD;
         26. Patients who are unable to comply with pulmonary medication restrictions prior to&#xD;
             randomisation.&#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>1222.52.02090 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Anniston</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02046 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02014 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Mobile</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02017 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Montgomery</city>
        <state>Alabama</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02092 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02072 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Chandler</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02063 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02088 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Peoria</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02012 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02006 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Huntington Beach</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02031 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>San Jose</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02011 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Torrance</city>
        <state>California</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02061 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Boulder</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02054 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02001 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02037 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Norwalk</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02055 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Waterbury</city>
        <state>Connecticut</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02094 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02022 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02074 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02016 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Ponte Verda</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02084 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>St. Petersberg</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02043 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02009 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Blue Ridge</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02048 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Duluth</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02077 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Gainsville</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02040 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Rincon</city>
        <state>Georgia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02024 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>O'Fallon</city>
        <state>Illinois</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02002 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Muncie</city>
        <state>Indiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02008 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Fort Mitchell</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02025 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02089 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02005 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02029 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Columbia</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02036 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hollywood</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02015 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Townson</city>
        <state>Maryland</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02034 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>North Dartmouth</city>
        <state>Massachusetts</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02003 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Chelsea</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02020 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Kalamazoo</city>
        <state>Michigan</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02047 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02049 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02079 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Plymouth</city>
        <state>Minnesota</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02068 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Chesterfield</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02028 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02053 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>St. Louis</city>
        <state>Missouri</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02050 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Billings</city>
        <state>Montana</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02035 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Henderson</city>
        <state>Nevada</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02030 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Marlton</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02071 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02064 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Johnson City</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02087 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>New Windsor</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02091 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02076 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Calabash</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02010 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Huntersville</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02045 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02038 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Salisbury</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02051 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Shelby</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02058 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Tabor City</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02013 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Winston Salem</city>
        <state>North Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02062 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02039 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02081 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02093 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02059 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02026 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02097 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Medford</city>
        <state>Oregon</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02075 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02102 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02080 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02100 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02096 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02085 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02101 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02065 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Hodges</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02042 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Myrtle Beach</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02083 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02066 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02095 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02098 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Union</city>
        <state>South Carolina</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02018 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Brentwood</city>
        <state>Tennessee</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02086 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Arlington</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02044 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Austin</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02041 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>El Paso</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02027 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Fort Worth</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02056 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02007 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02060 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02078 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Sugar Land</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02082 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Waco</city>
        <state>Texas</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02057 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Midvale</city>
        <state>Utah</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02023 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02069 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Selah</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02019 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>1222.52.02099 Boehringer Ingelheim Investigational Site</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://trials.boehringer-ingelheim.com/</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2014</verification_date>
  <study_first_submitted>September 26, 2012</study_first_submitted>
  <study_first_submitted_qc>September 26, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 28, 2012</study_first_posted>
  <results_first_submitted>September 5, 2014</results_first_submitted>
  <results_first_submitted_qc>November 5, 2014</results_first_submitted_qc>
  <results_first_posted type="Estimate">November 10, 2014</results_first_posted>
  <last_update_submitted>November 13, 2014</last_update_submitted>
  <last_update_submitted_qc>November 13, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">November 25, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tiotropium Bromide</mesh_term>
    <mesh_term>Olodaterol</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>1137 patients were entered and randomized to treatment and 1135 patients were treated with study medication.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
          <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose&#xD;
Tiotropium: Marketed dose</description>
        </group>
        <group group_id="P2">
          <title>Placebo and Tiotropium (18μg)</title>
          <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="566"/>
                <participants group_id="P2" count="569"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="523"/>
                <participants group_id="P2" count="538"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="43"/>
                <participants group_id="P2" count="31"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <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="2"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="6"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other reason prematurely discontinued</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated set (TS), which includes all randomized patients who receive at least one dose of double-blind study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
          <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose&#xD;
Tiotropium: Marketed dose</description>
        </group>
        <group group_id="B2">
          <title>Placebo and Tiotropium (18μg)</title>
          <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</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="566"/>
            <count group_id="B2" value="569"/>
            <count group_id="B3" value="1135"/>
          </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="64.6" spread="9.0"/>
                    <measurement group_id="B2" value="63.6" spread="8.9"/>
                    <measurement group_id="B3" value="64.1" spread="9.0"/>
                  </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="261"/>
                    <measurement group_id="B2" value="266"/>
                    <measurement group_id="B3" value="527"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="305"/>
                    <measurement group_id="B2" value="303"/>
                    <measurement group_id="B3" value="608"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12</title>
        <description>FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks. FAS included all patients in the treated set who had both baseline and at least one post-baseline measurement at or before 12 weeks for any of the co-primary efficacy variables</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12</title>
          <description>FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit.</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks. FAS included all patients in the treated set who had both baseline and at least one post-baseline measurement at or before 12 weeks for any of the co-primary efficacy variables</population>
          <units>Area Under the Curve (L) (standardized)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="563"/>
                <count group_id="O2" value="566"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.297" spread="0.010"/>
                    <measurement group_id="O2" value="0.191" spread="0.010"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an mixed model repeated measure (MMRM) model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used. Number of patients contributing to models: Tio+Placebo (566), Tio+Olo 5ug (563).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.106</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.014</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.078</ci_lower_limit>
            <ci_upper_limit>0.135</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12</title>
        <description>Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Full Analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12</title>
          <description>Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12</description>
          <population>Full Analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
          <units>L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="550"/>
                <count group_id="O2" value="555"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.175" spread="0.009"/>
                    <measurement group_id="O2" value="0.135" spread="0.009"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an MMRM model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used. Number of patients contributing to models: Tio+Placebo (555), Tio+Olo 5ug (550).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0029</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.040</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.013</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.014</ci_lower_limit>
            <ci_upper_limit>0.065</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data</title>
        <description>The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores [dichotomous (true/false) except last question (4-point Likert scale)]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols.</description>
        <time_frame>12 weeks</time_frame>
        <population>FAS with last observation carried forward (LOCF) imputation (combined data from twin studies 1222.51 and 1222.52). Number of patients contributing to models: Tio+Placebo (1055), Tio+Olo 5ug (1039).</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data</title>
          <description>The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores [dichotomous (true/false) except last question (4-point Likert scale)]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols.</description>
          <population>FAS with last observation carried forward (LOCF) imputation (combined data from twin studies 1222.51 and 1222.52). Number of patients contributing to models: Tio+Placebo (1055), Tio+Olo 5ug (1039).</population>
          <units>units on a scale (total score)</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1039"/>
                <count group_id="O2" value="1055"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="41.204" spread="0.327"/>
                    <measurement group_id="O2" value="43.059" spread="0.325"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from ANCOVA model. Fixed effects include study, treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (1055), Tio+Olo 5ug (1039).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>-1.854</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.461</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-2.757</ci_lower_limit>
            <ci_upper_limit>-0.951</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline</title>
        <description>Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline</title>
          <description>Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive.</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
          <units>L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="563"/>
                <count group_id="O2" value="566"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.371" spread="0.011"/>
                    <measurement group_id="O2" value="0.271" spread="0.011"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an MMRM model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used.&#xD;
Number of patients contributing to models: Tio+Placebo (566), Tio+Olo 5ug (563).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.100</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.015</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.071</ci_lower_limit>
            <ci_upper_limit>0.129</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline</title>
        <description>Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.</description>
        <time_frame>baseline and 12 Weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline</title>
          <description>Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
          <units>L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="563"/>
                <count group_id="O2" value="566"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.424" spread="0.017"/>
                    <measurement group_id="O2" value="0.306" spread="0.017"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an MMRM model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used.&#xD;
Number of patients contributing to models: Tio+Placebo (566), Tio+Olo 5ug (563).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.118</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.023</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.072</ci_lower_limit>
            <ci_upper_limit>0.164</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak FVC Response at 12 Weeks; Defined as Change From Baseline</title>
        <description>Peak FVC response at 12 weeks - defined as change from baseline.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Peak FVC Response at 12 Weeks; Defined as Change From Baseline</title>
          <description>Peak FVC response at 12 weeks - defined as change from baseline.</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation at 12 weeks.</population>
          <units>L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="563"/>
                <count group_id="O2" value="566"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.562" spread="0.017"/>
                    <measurement group_id="O2" value="0.457" spread="0.017"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an MMRM model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used.&#xD;
Number of patients contributing to models: Tio+Placebo (566), Tio+Olo 5ug (563).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.104</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.024</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.057</ci_lower_limit>
            <ci_upper_limit>0.152</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough FVC Response at 12 Weeks; Defined as Change From Baseline</title>
        <description>Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.</description>
        <time_frame>baseline and 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Trough FVC Response at 12 Weeks; Defined as Change From Baseline</title>
          <description>Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
          <units>L</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="550"/>
                <count group_id="O2" value="555"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.269" spread="0.015"/>
                    <measurement group_id="O2" value="0.235" spread="0.015"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Results are from an MMRM model. Fixed effects include treatment, visit, treatment by visit interaction, baseline and baseline by visit interaction. Patient is considered random and an unstructured covariance structure was used.&#xD;
Number of patients contributing to models: Tio+Placebo (555), Tio+Olo 5ug (550).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.1156</p_value>
            <method>Mixed Model Repeated Measure</method>
            <param_type>Mean Difference (Final Values)</param_type>
            <param_value>0.034</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.022</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.008</ci_lower_limit>
            <ci_upper_limit>0.076</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rescue Medication Usage - Percentage of Rescue Free Days</title>
        <description>Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment).&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)</description>
        <time_frame>over 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Rescue Medication Usage - Percentage of Rescue Free Days</title>
          <description>Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment).&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
          <units>percentage of days</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="552"/>
                <count group_id="O2" value="559"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53.207" spread="1.481"/>
                    <measurement group_id="O2" value="48.583" spread="1.472"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.249" spread="48.640"/>
                    <measurement group_id="O2" value="48.640" spread="1.477"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.820" spread="1.536"/>
                    <measurement group_id="O2" value="49.865" spread="1.528"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.761" spread="1.388"/>
                    <measurement group_id="O2" value="55.969" spread="1.378"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.154" spread="1.550"/>
                    <measurement group_id="O2" value="51.840" spread="1.549"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.707" spread="1.572"/>
                    <measurement group_id="O2" value="49.001" spread="1.568"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.493" spread="1.598"/>
                    <measurement group_id="O2" value="50.164" spread="1.594"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.021" spread="1.634"/>
                    <measurement group_id="O2" value="51.017" spread="1.626"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.524" spread="1.636"/>
                    <measurement group_id="O2" value="51.273" spread="1.620"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="60.216" spread="1.636"/>
                    <measurement group_id="O2" value="51.634" spread="1.616"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="59.650" spread="1.636"/>
                    <measurement group_id="O2" value="51.604" spread="1.616"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="62.327" spread="1.525"/>
                    <measurement group_id="O2" value="55.090" spread="1.508"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 12: Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0008</p_value>
            <method>ANCOVA</method>
            <param_type>Mean difference from Tio+Placebo Week 12</param_type>
            <param_value>7.237</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>2.145</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>3.028</ci_lower_limit>
            <ci_upper_limit>11.446</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)</title>
        <description>Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
        <time_frame>over 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)</title>
          <description>Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
          <units>usage (total daily) number of puffs</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="555"/>
                <count group_id="O2" value="559"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.627" spread="0.066"/>
                    <measurement group_id="O2" value="2.072" spread="0.066"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.652" spread="0.072"/>
                    <measurement group_id="O2" value="2.145" spread="0.072"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.635" spread="0.078"/>
                    <measurement group_id="O2" value="2.167" spread="0.078"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.647" spread="0.081"/>
                    <measurement group_id="O2" value="2.189" spread="0.080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.551" spread="0.081"/>
                    <measurement group_id="O2" value="2.183" spread="0.080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.523" spread="0.081"/>
                    <measurement group_id="O2" value="2.179" spread="0.080"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.540" spread="0.083"/>
                    <measurement group_id="O2" value="2.138" spread="0.082"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.586" spread="0.085"/>
                    <measurement group_id="O2" value="2.107" spread="0.084"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.519" spread="0.083"/>
                    <measurement group_id="O2" value="2.121" spread="0.082"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.499" spread="0.082"/>
                    <measurement group_id="O2" value="2.103" spread="0.081"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.484" spread="0.083"/>
                    <measurement group_id="O2" value="2.107" spread="0.082"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.535" spread="0.084"/>
                    <measurement group_id="O2" value="2.103" spread="0.083"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 12 - Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Mean difference from Tio+Placebo Week 12</param_type>
            <param_value>-0.568</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.118</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.800</ci_lower_limit>
            <ci_upper_limit>-0.336</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)</title>
        <description>Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
        <time_frame>over 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)</title>
          <description>Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
          <units>number of puffs</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="555"/>
                <count group_id="O2" value="559"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.406" spread="0.025"/>
                    <measurement group_id="O2" value="0.437" spread="0.025"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.421" spread="0.027"/>
                    <measurement group_id="O2" value="0.466" spread="0.027"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.407" spread="0.030"/>
                    <measurement group_id="O2" value="0.459" spread="0.030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.408" spread="0.031"/>
                    <measurement group_id="O2" value="0.479" spread="0.031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.375" spread="0.030"/>
                    <measurement group_id="O2" value="0.479" spread="0.030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.378" spread="0.030"/>
                    <measurement group_id="O2" value="0.491" spread="0.030"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.403" spread="0.033"/>
                    <measurement group_id="O2" value="0.499" spread="0.032"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.417" spread="0.033"/>
                    <measurement group_id="O2" value="0.482" spread="0.033"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.396" spread="0.033"/>
                    <measurement group_id="O2" value="0.487" spread="0.032"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.392" spread="0.032"/>
                    <measurement group_id="O2" value="0.480" spread="0.031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.383" spread="0.031"/>
                    <measurement group_id="O2" value="0.482" spread="0.031"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.393" spread="0.032"/>
                    <measurement group_id="O2" value="0.483" spread="0.032"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 12 - Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.0467</p_value>
            <method>ANCOVA</method>
            <param_type>Mean difference from Tio+Placebo Week 1</param_type>
            <param_value>-0.090</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.045</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.178</ci_lower_limit>
            <ci_upper_limit>-0.001</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)</title>
        <description>Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
        <time_frame>over 12 weeks</time_frame>
        <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
        <group_list>
          <group group_id="O1">
            <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
            <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
          </group>
          <group group_id="O2">
            <title>Placebo and Tiotropium (18μg)</title>
            <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
          </group>
        </group_list>
        <measure>
          <title>Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)</title>
          <description>Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.&#xD;
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)</description>
          <population>Full analysis set (FAS) with last observation carried forward (LOCF) imputation</population>
          <units>number of puffs</units>
          <param>Least Squares Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="555"/>
                <count group_id="O2" value="559"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.222" spread="0.055"/>
                    <measurement group_id="O2" value="1.633" spread="0.055"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.232" spread="0.058"/>
                    <measurement group_id="O2" value="1.677" spread="0.058"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.229" spread="0.062"/>
                    <measurement group_id="O2" value="1.707" spread="0.062"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.239" spread="0.064"/>
                    <measurement group_id="O2" value="1.709" spread="0.064"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 5</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.177" spread="0.065"/>
                    <measurement group_id="O2" value="1.710" spread="0.064"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.148" spread="0.065"/>
                    <measurement group_id="O2" value="1.692" spread="0.064"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 7</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.139" spread="0.065"/>
                    <measurement group_id="O2" value="1.641" spread="0.064"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.173" spread="0.067"/>
                    <measurement group_id="O2" value="1.628" spread="0.066"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 9</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.125" spread="0.065"/>
                    <measurement group_id="O2" value="1.636" spread="0.065"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.108" spread="0.066"/>
                    <measurement group_id="O2" value="1.630" spread="0.065"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 11</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.104" spread="0.067"/>
                    <measurement group_id="O2" value="1.630" spread="0.066"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.143" spread="0.067"/>
                    <measurement group_id="O2" value="1.625" spread="0.066"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Week 12 - Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.&#xD;
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555).</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;.0001</p_value>
            <method>ANCOVA</method>
            <param_type>Mean difference from Tio+Placebo Week 12</param_type>
            <param_value>-0.483</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.094</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.668</ci_lower_limit>
            <ci_upper_limit>-0.298</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were to be documented throughout the trial, i.e., starting with informed consent and ending 21 days after last administration of trial medication. the duration of treatment was up to 12 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Olodaterol (5μg) and Tiotropium (18μg)</title>
          <description>2 puffs olodaterol from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Olodaterol: One dose, 2 inhalations once daily in the morning&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning</description>
        </group>
        <group group_id="E2">
          <title>Placebo and Tiotropium (18μg)</title>
          <description>2 puffs placebo inhalation solution from Respimat and one capsule tiotropium from Handihaler once daily in am, co-administered&#xD;
Tiotropium: Marketed dose, 2 inhalations from 1 capsule once daily in the morning&#xD;
Placebo matching Olodaterol: One dose, 2 inhalations once daily in the morning</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MEDDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Acute myocardial infarction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Angina unstable</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Atrial flutter</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Cardiac arrest</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Coronary artery disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Abdominal pain upper</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Gastritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Haemorrhoids</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Lower gastrointestinal haemorrhage</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Oesophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Small intestinal obstruction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Death</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Sudden death</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaphylactic reaction</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Cellulitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Multiple injuries</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Postoperative renal failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Rib fracture</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Toxicity to various agents</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Flank pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Adenocarcinoma gastric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Breast cancer</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Plasma cell myeloma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Convulsion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Transient ischaemic attack</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus ureteric</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Renal colic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </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="2" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Pleuritic pain</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic aneurysm</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="569"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MEDDRA 16.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="48" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="569"/>
              </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="48" subjects_at_risk="566"/>
                <counts group_id="E2" subjects_affected="44" subjects_at_risk="569"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

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


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01696058
org study id: 1222.52
nct id: NCT01696058
lead sponsor: 
The overall objective of this study is to assess efficacy and safety of 12 weeks, once daily,
      orally inhaled co-administration of olodaterol 5 µg (delivered by the Respimat® Inhaler) and
      tiotropium (delivered by the Handihaler® as Spiriva Handihaler®), compared to tiotropium
      (Spiriva Handihaler®) monotherapy on lung function in patients with COPD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double
measure: FEV1 AUC0-3h Response at 12 Weeks; Defined as Change From Baseline to Week 12
time frame: baseline and 12 weeks
description: FEV1 (Forced expiratory volume in 1 second) AUC0-3h (area under the curve) response at 12 weeks; defined as change from baseline to Week 12. AUC was standardized by dividing by time unit.
measure: Trough FEV1 Response at 12 Weeks; Defined as Change From Baseline to Week 12
time frame: baseline and 12 weeks
description: Trough FEV1 (Forced expiratory volume in 1 second) response at 12 weeks; defined as change from baseline to Week 12
measure: Saint George Respiratory Questionnaire - (Total Score) Based on Combined 1222.51 and 1222.52 Data
time frame: 12 weeks
description: The Saint George Respiratory Questionnaire (SGRQ) is designed to measure health impairment in patients with asthma and chronic obstructive pulmonary disease (COPD). It is divided into two parts. Part I produces the Symptoms score (several scales), and Part II the Activity and Impacts scores [dichotomous (true/false) except last question (4-point Likert scale)]. A Total score is also produced with scores ranging from 0 to 100, with higher scores indicating more limitations. Since the SGRQ analysis is based on the combined data from both this study and protocol 1222.51 (NCT01694771), only combined SGRQ results will be included in the latest clinical trial report. Hence there will only be one SGRQ analysis from both studies, which will not appear in the first clinical trial report. For this same reason, another covariate - study - will also be included in the MMRM for SGRQ analysis. The combined data for this outcome measure was pre-specified in both protocols.
measure: Peak FEV1 Response at 12 Weeks - Defined as Change From Baseline
time frame: baseline and 12 weeks
description: Peak FEV1 (Forced Expiratory Volume in 1 second) response at 12 Weeks - defined as change from baseline. All p-values for these measures are only descriptive.
measure: FVC AUC0-3h Response at 12 Weeks; Defined as Change From Baseline
time frame: baseline and 12 Weeks
description: Forced Vital Capacity (FVC) AUC0-3h response at 12 weeks - defined as change from baseline. AUC was standardized by dividing by time unit.
measure: Peak FVC Response at 12 Weeks; Defined as Change From Baseline
time frame: baseline and 12 weeks
description: Peak FVC response at 12 weeks - defined as change from baseline.
measure: Trough FVC Response at 12 Weeks; Defined as Change From Baseline
time frame: baseline and 12 weeks
description: Trough Forced Vital Capacity (FVC) response at 12 weeks- defined as change from baseline.
measure: Rescue Medication Usage - Percentage of Rescue Free Days
time frame: over 12 weeks
description: Rescue medication usage - the percentage of rescue free days. The percentage of rescue free days is defined as: number of rescue free days divided by total exposure, multiplied by 100%. The baseline for the number of rescue-free days was defined as the number of rescue-free days observed during the last week of the baseline period (i.e., the 7 days prior to administration of the first dose of randomized treatment).
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (552)
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Total Daily)
time frame: over 12 weeks
description: Rescue medication usage - mean weekly rescue usage (total daily). The baseline for the rescue use was the mean of the observations during the last week of the baseline period. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol metered dose inhaler (MDI) (100 μg per puff) was provided as rescue medication . Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Daytime)
time frame: over 12 weeks
description: Rescue medication usage - Mean weekly rescue usage during daytime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
measure: Rescue Medication Usage - Mean Weekly Rescue Usage (Nighttime)
time frame: over 12 weeks
description: Rescue medication usage - Mean weekly rescue usage during nighttime hours. Administration of rescue medication could occur at any point during the trial as deemed necessary by the patient or the investigator. Open label albuterol MDI (100 μg per puff) was provided as rescue medication by BI, and only the albuterol MDI provided by BI was allowed for rescue medication use. Daily, between clinic visits, patients recorded the number of puffs of albuterol in a paper diary.
Results are from non-MMRM ANCOVA models by week with LOCF up to each week. Fixed effects include treatment and baseline.
Number of patients contributing to models: Tio+Placebo (559), Tio+Olo 5ug (555)
arm group label: Olodaterol andTiotropium
arm group type: Experimental
description: 2 puffs Olodaterol from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
arm group label: Placebo and Tiotropium
arm group type: Other
description: 2 puffs placebo inhalation solution from Respimat and one capsule Tiotropium by Handihaler once daily in am, co-administered
intervention type: Drug
intervention name: Tiotropium
description: marketed product
arm group label: Placebo and Tiotropium
intervention type: Drug
intervention name: Placebo matching Olodaterol
description: one dose
arm group label: Placebo and Tiotropium
intervention type: Drug
intervention name: Tiotropium
description: marketed product
arm group label: Olodaterol andTiotropium
intervention type: Drug
intervention name: Olodaterol
description: one dose
arm group label: Olodaterol andTiotropium
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
url: http://trials.boehringer-ingelheim.com/
description: Related Info
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Tiotropium Bromide
mesh term: Olodaterol
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 