<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/NCT03240575</url>
  </required_header>
  <id_info>
    <org_study_id>1237-0063</org_study_id>
    <nct_id>NCT03240575</nct_id>
  </id_info>
  <brief_title>The ENERGITO® 2 Study Compares 2 Inhaled Medicines for Chronic Obstructive Pulmonary Disease (COPD). One Medicine is a Combination of Tiotropium and Olodaterol (Stiolto®) Taken Using the Respimat® Inhaler and the Other Medicine is a Combination of Fluticasone and Salmeterol Taken Using the Diskus</brief_title>
  <official_title>A Randomized, Double-blind, Double-dummy, Active-controlled, Multi-center, Parallel Group Study to Show the Superiority in Lung Function of 12 Weeks Once Daily Treatment With Orally Inhaled Tiotropium+Olodaterol Fixed Dose Combination Delivered by the Respimat® Inhaler vs. 12 Weeks Twice Daily Treatment With Fluticasone Propionate+Salmeterol Fixed Dose Combination Delivered by the Diskus® in Patients With Chronic Obstructive Pulmonary Disease (COPD) [ENERGITO® 2]</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of the trial is to show superiority in lung function of once daily (2&#xD;
      inhalations) treatment with orally inhaled tiotropium+olodaterol fixed dose combination to&#xD;
      twice daily (one inhalation) treatment with fluticasone propionate+salmeterol fixed dose&#xD;
      combination over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD).&#xD;
&#xD;
      A Digital Health (DH) exploratory study has been integrated into the main study as a site&#xD;
      specific study. The DH exploratory study will be performed at a single site; the site is also&#xD;
      participating in the main study. The DH exploratory study site will enter (randomize)&#xD;
      approximately 20 patients (subjects) (in addition to the patients to be enrolled in the main&#xD;
      study at this site). The patients enrolled in the DH exploratory study are not considered to&#xD;
      be part of the main study (i.e. data collected in the DH exploratory study will be analyzed&#xD;
      separately from the data collected in the main study).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 14, 2017</start_date>
  <completion_date type="Actual">May 6, 2019</completion_date>
  <primary_completion_date type="Actual">April 8, 2019</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment</measure>
    <time_frame>1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline.10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min, 12h 30 min, 13h, 14h, 22h, 23h, and 24h post morning dose at week 12.</time_frame>
    <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 24 hours (AUC0-24) response (change from baseline) [L] after 12 weeks of treatment. FEV1 AUC0-24 was calculated as the area under the FEV1-time curve from 0-24 hours post-dose using the trapezoidal rule, divided by the duration (24 hours) and reported in liters. FEV1 AUC0-24 response (change from baseline) was defined as FEV1 AUC0-24 mius baseline FEV1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment</measure>
    <time_frame>1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline. 10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min post morning dose at week 12.</time_frame>
    <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 12 hours (AUC0-12) response (change from baseline) [L] after 12 weeks of treatment.&#xD;
FEV1 AUC0-12 was calculated as the area under the FEV1-time curve from 0-12 hours post-dose using the trapezoidal rule, divided by the duration (12 hours) and reported in liters. FEV1 AUC0-12 response (change from baseline) was defined as FEV1 AUC0-12 minus baseline FEV1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</measure>
    <time_frame>At 23 h and 24 h post dose at baseline and at 23h and 24 h post dose at week 12.</time_frame>
    <description>Trough Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Trough FEV1 was defined as the mean of the FEV1 value measured at 23 hours and at 24 hours after the trial medication administration. Through FEV1 response (change from baseline) was defined as trough FEV1 minus baseline FEV1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</measure>
    <time_frame>30 minutes, 1 h, 2h and 3h post dose at baseline and week 12.</time_frame>
    <description>Peak 0-3 hours Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Peak 0-3h was defined as the maximum value measured within the first three hours post doing.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">302</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Tiotropium + Olodaterol fixed dose combination</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Fluticasone propionate + Salmeterol fixed dose combination</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tiotropium</intervention_name>
    <description>Fixed Dose Combination</description>
    <arm_group_label>Tiotropium + Olodaterol fixed dose combination</arm_group_label>
    <other_name>INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Olodaterol</intervention_name>
    <description>Fixed Dose Combination</description>
    <arm_group_label>Tiotropium + Olodaterol fixed dose combination</arm_group_label>
    <other_name>INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluticasone propionate</intervention_name>
    <description>Fixed Dose Combination</description>
    <arm_group_label>Fluticasone propionate + Salmeterol fixed dose combination</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Salmeterol</intervention_name>
    <description>Fixed Dose Combination</description>
    <arm_group_label>Fluticasone propionate + Salmeterol fixed dose combination</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients must sign an informed consent consistent with FDA regulations prior to&#xD;
             participation in the trial, which includes medication washout and restrictions.&#xD;
&#xD;
          -  All patients must have a diagnosis of chronic obstructive pulmonary disease and must&#xD;
             meet the following spirometric criteria:&#xD;
&#xD;
             -- Patients with a post-bronchodilator 30% ≤ Forced Expiratory Volume in one second&#xD;
             (FEV1) &lt;80% of predicted normal (European Coal and Steel Community( ECSC)); and a&#xD;
             post-bronchodilator FEV1/Forced Vital Capacity (FVC) &lt;70% at Visit 1&#xD;
&#xD;
          -  Male or female patients, 40 years of age or older.&#xD;
&#xD;
          -  Patients must be current or ex-smokers with a smoking history of more than 10 pack&#xD;
             years. Patients who have never smoked cigarettes must be excluded.&#xD;
&#xD;
          -  Patients must be able to perform, according to investigator's judgment, all trial&#xD;
             related procedures including:&#xD;
&#xD;
               -  Technically acceptable pulmonary function tests (spirometry)&#xD;
&#xD;
               -  Completion of study questionnaires&#xD;
&#xD;
          -  Patients must be able to inhale medication in a competent manner (in the opinion of&#xD;
             the investigator) from the Respimat® and Diskus® inhalers and from a metered dose&#xD;
             inhaler (MDI).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with a significant disease other than Chronic Obstructive Pulmonary Disease&#xD;
             (COPD); a significant disease is defined as a disease which, in the opinion of the&#xD;
             investigator, may (i) put the patient at risk because of participation in the study,&#xD;
             (ii) influence the results of the study, or (iii) cause concern regarding the&#xD;
             patient's ability to participate in the study.&#xD;
&#xD;
          -  Patients who have had a COPD exacerbation that required treatment with antibiotics,&#xD;
             systemic steroids (oral or intravenous) or hospitalization in the last 3 months prior&#xD;
             to Visit 1 and/or between Visit 1 and Visit 2.&#xD;
&#xD;
          -  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 nonasthmatic condition.&#xD;
&#xD;
        Patients with any of the following conditions:&#xD;
&#xD;
          -  A diagnosis of thyrotoxicosis (due to the known class side effect profile of&#xD;
             ß2-agonists).&#xD;
&#xD;
          -  A diagnosis of paroxysmal tachycardia (&gt;100 beats per minute) (due to the known class&#xD;
             side effect profile of ß2-agonists).&#xD;
&#xD;
          -  A history of myocardial infarction within 1 year of screening visit (Visit 1).&#xD;
&#xD;
          -  Unstable or life-threatening cardiac arrhythmia.&#xD;
&#xD;
          -  Hospitalization for heart failure within the past year.&#xD;
&#xD;
          -  Known active tuberculosis.&#xD;
&#xD;
          -  A malignancy for which patient has undergone resection, radiation therapy or&#xD;
             chemotherapy within last five years (patients with treated basal cell carcinoma are&#xD;
             allowed).&#xD;
&#xD;
          -  A history of life-threatening pulmonary obstruction.&#xD;
&#xD;
          -  A history of cystic fibrosis.&#xD;
&#xD;
          -  Clinically evident bronchiectasis.&#xD;
&#xD;
          -  A history of significant alcohol or drug abuse.&#xD;
&#xD;
          -  Patients who have undergone thoracotomy with pulmonary resection (patients with a&#xD;
             history of thoracotomy for other reasons should be evaluated as per the first&#xD;
             exclusion criterion).&#xD;
&#xD;
          -  Patients being treated with oral or patch β-adrenergics.&#xD;
&#xD;
          -  Patients being treated with oral corticosteroid medication within 6 weeks prior to&#xD;
             Visit 1.&#xD;
&#xD;
          -  Patients who regularly use daytime oxygen therapy for more than one hour per day and&#xD;
             in the investigator's opinion will be unable to abstain from the use of oxygen therapy&#xD;
             during clinic visits.&#xD;
&#xD;
          -  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;
          -  Patients who have taken an investigational drug within one month, six half-lives or&#xD;
             within the wash out period (whichever is greater) prior to screening visit (Visit 1).&#xD;
&#xD;
          -  Patients with known hypersensitivity to β-adrenergic drugs, BAC, EDTA, or any other&#xD;
             component of the Respimat® inhalation solution. In addition, patients with known&#xD;
             hypersensitivity to Lactose monohydrate (which contains milk proteins).&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
&#xD;
          -  Women of childbearing potential not using a method of birth control classified at&#xD;
             least as &quot;acceptable&quot;. Female patients will be considered to be of childbearing&#xD;
             potential unless surgically sterilized by hysterectomy, bilateral salpingectomy,&#xD;
             bilateral oophorectomy, or post-menopausal (defined as no menses for 12 months without&#xD;
             an alternative medical cause). Tubal ligation is NOT a method of permanent&#xD;
             sterilisation.&#xD;
&#xD;
          -  Patients who have previously been randomized in this study or are currently&#xD;
             participating in another study.&#xD;
&#xD;
          -  Patients who are unable to comply with pulmonary medication restrictions prior to&#xD;
             randomization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Jasper Summit Research, LLC</name>
      <address>
        <city>Jasper</city>
        <state>Alabama</state>
        <zip>35501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Trial Connection</name>
      <address>
        <city>Flagstaff</city>
        <state>Arizona</state>
        <zip>86001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Research Medical Group, Inc.</name>
      <address>
        <city>Fullerton</city>
        <state>California</state>
        <zip>92835</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allergy and Asthma Specialists Medical Group</name>
      <address>
        <city>Huntington Beach</city>
        <state>California</state>
        <zip>92647</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>California Medical Research Associates Inc.</name>
      <address>
        <city>Northridge</city>
        <state>California</state>
        <zip>91324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IMMUNOe Research Centers</name>
      <address>
        <city>Centennial</city>
        <state>Colorado</state>
        <zip>80112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida, Inc.</name>
      <address>
        <city>Clearwater</city>
        <state>Florida</state>
        <zip>33765</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bioclinica Research</name>
      <address>
        <city>Orlando</city>
        <state>Florida</state>
        <zip>32806</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IMIC, Inc</name>
      <address>
        <city>Palmetto Bay</city>
        <state>Florida</state>
        <zip>33157</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida, Inc.</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duluth Biomedical Research</name>
      <address>
        <city>Duluth</city>
        <state>Georgia</state>
        <zip>30096</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DC Pulmonary Medicine</name>
      <address>
        <city>Marietta</city>
        <state>Georgia</state>
        <zip>30060</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Orleans Center for Clinical Research</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21224</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Rsrch Inst of SE MI</name>
      <address>
        <city>Farmington Hills</city>
        <state>Michigan</state>
        <zip>48336</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Lung Center and Sleep Institute</name>
      <address>
        <city>Edina</city>
        <state>Minnesota</state>
        <zip>55435</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research Institute Inc</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55402</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minnesota Lung Center</name>
      <address>
        <city>Woodbury</city>
        <state>Minnesota</state>
        <zip>55125</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Clinical Research Center, LLC</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwell Health</name>
      <address>
        <city>New Hyde Park</city>
        <state>New York</state>
        <zip>11040</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gastonia Pharmaceutical Research, LLC</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hendersonville Pharmaceutical Research</name>
      <address>
        <city>Hendersonville</city>
        <state>North Carolina</state>
        <zip>28739</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Carolina Clinical Research</name>
      <address>
        <city>Raleigh</city>
        <state>North Carolina</state>
        <zip>27607</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southeastern Research Center</name>
      <address>
        <city>Winston-Salem</city>
        <state>North Carolina</state>
        <zip>27103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bernstein Clinical Rsrch Ctr</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aventiv Research Inc.</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aventiv Research Inc.</name>
      <address>
        <city>Dublin</city>
        <state>Ohio</state>
        <zip>43016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>OK Clinical Research, LLC</name>
      <address>
        <city>Edmond</city>
        <state>Oklahoma</state>
        <zip>73034</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>IPS Research Company</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73103</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arcuri Clinical Research, LLC</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19142</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lowcountry Lung and Critical Care</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research - Easley</name>
      <address>
        <city>Easley</city>
        <state>South Carolina</state>
        <zip>29640</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research -Gaffney</name>
      <address>
        <city>Gaffney</city>
        <state>South Carolina</state>
        <zip>29340</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VitaLink Research</name>
      <address>
        <city>Greenville</city>
        <state>South Carolina</state>
        <zip>29615</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vita Link Research- Rock Hill</name>
      <address>
        <city>Rock Hill</city>
        <state>South Carolina</state>
        <zip>29732</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Carolina Pharma Rsrch</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spartanburg Medical Research</name>
      <address>
        <city>Spartanburg</city>
        <state>South Carolina</state>
        <zip>29303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centex Studies, Inc.</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77058</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Clinical Research Associates</name>
      <address>
        <city>Plano</city>
        <state>Texas</state>
        <zip>75093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sherman Clinical Research</name>
      <address>
        <city>Sherman</city>
        <state>Texas</state>
        <zip>75092</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DM Clinical Research</name>
      <address>
        <city>Tomball</city>
        <state>Texas</state>
        <zip>77375</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23225</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pulmonary Associates of Richmond, Inc.</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MultiCare Institute for Research and Innovation</name>
      <address>
        <city>Tacoma</city>
        <state>Washington</state>
        <zip>98405</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Morgantown Pulmonary ClinRsrch</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26505</zip>
        <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>April 2020</verification_date>
  <study_first_submitted>July 27, 2017</study_first_submitted>
  <study_first_submitted_qc>August 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <results_first_submitted>April 3, 2020</results_first_submitted>
  <results_first_submitted_qc>April 3, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">April 16, 2020</results_first_posted>
  <last_update_submitted>April 3, 2020</last_update_submitted>
  <last_update_submitted_qc>April 3, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 16, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
    <mesh_term>Lung Diseases, Obstructive</mesh_term>
    <mesh_term>Pulmonary Disease, Chronic Obstructive</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluticasone</mesh_term>
    <mesh_term>Xhance</mesh_term>
    <mesh_term>Tiotropium Bromide</mesh_term>
    <mesh_term>Salmeterol Xinafoate</mesh_term>
    <mesh_term>Olodaterol</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03240575/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 6, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/75/NCT03240575/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study compares treatment tiotropium+olodaterol (5μg/5μg) once daily FDC to Fluticasone propionate+Salmeterol (250μg/50μg) twice daily FDC over 12 weeks in patients with COPD. A Digital Health (DH)-study has been integrated a site specific study. The patients enrolled in the DH-study are not considered to be part of the main study.</recruitment_details>
      <pre_assignment_details>All subjects were screened for eligibility prior to participation in the trial. Subjects attended a specialist site which ensured that they (the subjects) strictly met all inclusion and non of the exclusion criteria. Subjects were not to be allocated to a treatment group if any of the entry criteria were violated.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
        </group>
        <group group_id="P2">
          <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
        </group>
        <group group_id="P3">
          <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
        </group>
        <group group_id="P4">
          <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="146"/>
                <participants group_id="P2" count="145"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="144"/>
                <participants group_id="P2" count="131"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="14"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Treated Set (TS): All randomized patients who had taken at least one dose of study drug were included in the treated set.</population>
      <group_list>
        <group group_id="B1">
          <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
        </group>
        <group group_id="B2">
          <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
        </group>
        <group group_id="B3">
          <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
        </group>
        <group group_id="B4">
          <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
          <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
        </group>
        <group group_id="B5">
          <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="146"/>
            <count group_id="B2" value="145"/>
            <count group_id="B3" value="6"/>
            <count group_id="B4" value="5"/>
            <count group_id="B5" value="302"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.95" spread="8.32"/>
                    <measurement group_id="B2" value="64.74" spread="7.33"/>
                    <measurement group_id="B3" value="71.00" spread="4.77"/>
                    <measurement group_id="B4" value="60.00" spread="4.58"/>
                    <measurement group_id="B5" value="63.44" spread="7.81"/>
                  </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="72"/>
                    <measurement group_id="B2" value="62"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="4"/>
                    <measurement group_id="B5" value="139"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="74"/>
                    <measurement group_id="B2" value="83"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="163"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="144"/>
                    <measurement group_id="B2" value="143"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="298"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="132"/>
                    <measurement group_id="B2" value="127"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="5"/>
                    <measurement group_id="B5" value="270"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment</title>
        <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 24 hours (AUC0-24) response (change from baseline) [L] after 12 weeks of treatment. FEV1 AUC0-24 was calculated as the area under the FEV1-time curve from 0-24 hours post-dose using the trapezoidal rule, divided by the duration (24 hours) and reported in liters. FEV1 AUC0-24 response (change from baseline) was defined as FEV1 AUC0-24 mius baseline FEV1.</description>
        <time_frame>1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline.10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min, 12h 30 min, 13h, 14h, 22h, 23h, and 24h post morning dose at week 12.</time_frame>
        <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment</title>
          <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 24 hours (AUC0-24) response (change from baseline) [L] after 12 weeks of treatment. FEV1 AUC0-24 was calculated as the area under the FEV1-time curve from 0-24 hours post-dose using the trapezoidal rule, divided by the duration (24 hours) and reported in liters. FEV1 AUC0-24 response (change from baseline) was defined as FEV1 AUC0-24 mius baseline FEV1.</description>
          <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
          <units>Litre*hours (L*h)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
                <count group_id="O2" value="138"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.174" spread="0.019"/>
                    <measurement group_id="O2" value="0.122" spread="0.019"/>
                    <measurement group_id="O3" value="NA" spread="NA">Due to the small number of subjects and due to the many out of window test assessments, the primary endpoint could not be evaluated.</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">Due to the small number of subjects and due to the many out of window test assessments, the primary endpoint could not be evaluated.</measurement>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0543</p_value>
            <method>Mixed-effects model repeated measures</method>
            <method_desc>Treatment, visit and treatment by visit interaction as fixed effects, and baseline as well as baseline by visit interaction as covariates.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.052</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.027</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.001</ci_lower_limit>
            <ci_upper_limit>0.105</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment</title>
        <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 12 hours (AUC0-12) response (change from baseline) [L] after 12 weeks of treatment.&#xD;
FEV1 AUC0-12 was calculated as the area under the FEV1-time curve from 0-12 hours post-dose using the trapezoidal rule, divided by the duration (12 hours) and reported in liters. FEV1 AUC0-12 response (change from baseline) was defined as FEV1 AUC0-12 minus baseline FEV1.</description>
        <time_frame>1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline. 10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min post morning dose at week 12.</time_frame>
        <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
        </group_list>
        <measure>
          <title>Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment</title>
          <description>Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 12 hours (AUC0-12) response (change from baseline) [L] after 12 weeks of treatment.&#xD;
FEV1 AUC0-12 was calculated as the area under the FEV1-time curve from 0-12 hours post-dose using the trapezoidal rule, divided by the duration (12 hours) and reported in liters. FEV1 AUC0-12 response (change from baseline) was defined as FEV1 AUC0-12 minus baseline FEV1.</description>
          <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
          <units>Litre*hours (L*h)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
                <count group_id="O2" value="138"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.237" spread="0.019"/>
                    <measurement group_id="O2" value="0.147" spread="0.020"/>
                    <measurement group_id="O3" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0011</p_value>
            <method>Mixed-effects model repeated measures</method>
            <method_desc>Treatment, visit and treatment by visit interaction as fixed effects, and baseline as well as baseline by visit interaction as covariates.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.090</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.027</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.037</ci_lower_limit>
            <ci_upper_limit>0.144</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</title>
        <description>Trough Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Trough FEV1 was defined as the mean of the FEV1 value measured at 23 hours and at 24 hours after the trial medication administration. Through FEV1 response (change from baseline) was defined as trough FEV1 minus baseline FEV1.</description>
        <time_frame>At 23 h and 24 h post dose at baseline and at 23h and 24 h post dose at week 12.</time_frame>
        <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
        </group_list>
        <measure>
          <title>Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</title>
          <description>Trough Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Trough FEV1 was defined as the mean of the FEV1 value measured at 23 hours and at 24 hours after the trial medication administration. Through FEV1 response (change from baseline) was defined as trough FEV1 minus baseline FEV1.</description>
          <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
          <units>Litre (L)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="145"/>
                <count group_id="O2" value="138"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.118" spread="0.019"/>
                    <measurement group_id="O2" value="0.114" spread="0.019"/>
                    <measurement group_id="O3" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8593</p_value>
            <method>Mixed-effects model repeated measures</method>
            <method_desc>Treatment, visit and treatment by visit interaction as fixed effects, and baseline as well as baseline by visit interaction as covariates.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.005</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.027</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.048</ci_lower_limit>
            <ci_upper_limit>0.058</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</title>
        <description>Peak 0-3 hours Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Peak 0-3h was defined as the maximum value measured within the first three hours post doing.</description>
        <time_frame>30 minutes, 1 h, 2h and 3h post dose at baseline and week 12.</time_frame>
        <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
        <group_list>
          <group group_id="O1">
            <title>Tiotropium+Olodaterol (5μg/5μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O2">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - Main Study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the main study were not eligible to participate in the DH study.</description>
          </group>
          <group group_id="O3">
            <title>Tiotropium+Olodaterol (5μg/5μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 2.5 microgram (μg) tiotropium and 2.5μg olodaterol (T+O) (total 5μg/5μg) were administered orally once daily in the morning via RESPIMAT inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
          <group group_id="O4">
            <title>Fluticasone Propionate+Salmeterol (500μg/100μg) - DH-study</title>
            <description>2 inhalations of fixed dose combination (FDC) of 250μg fluticasone propionate and 50μg salmeterol (F+S) (total 500μg/100μg) were administered orally twice daily in the morning and in the evening (12h after morning dose) via Diskus inhaler over a treatment period of 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients enrolled in the DH study were not eligible to participate in the main study.</description>
          </group>
        </group_list>
        <measure>
          <title>Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment</title>
          <description>Peak 0-3 hours Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Peak 0-3h was defined as the maximum value measured within the first three hours post doing.</description>
          <population>Full Analysis Set (FAS): FAS included all patients in the TS who had baseline and at least one post-baseline measurement for at least one efficacy parameter. The Mixed-effects model repeated measurement (MMRM) model defined the participants who contributed to the model.</population>
          <units>Litre (L)</units>
          <param>Mean</param>
          <dispersion>Standard Error</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="144"/>
                <count group_id="O2" value="138"/>
                <count group_id="O3" value="6"/>
                <count group_id="O4" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.341" spread="0.021"/>
                    <measurement group_id="O2" value="0.243" spread="0.021"/>
                    <measurement group_id="O3" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                    <measurement group_id="O4" value="NA" spread="NA">Based on the exploratory study design of the DH-study and the small number of patients, Endpoints were planned to be analyzed descriptively.</measurement>
                  </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>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0010</p_value>
            <method>Mixed-effects model repeated measures</method>
            <method_desc>Treatment, visit and treatment by visit interaction as fixed effects, and baseline as well as baseline by visit interaction as covariates.</method_desc>
            <param_type>Mean Difference (Net)</param_type>
            <param_value>0.098</param_value>
            <dispersion_type>Standard Error of the Mean</dispersion_type>
            <dispersion_value>0.029</dispersion_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.040</ci_lower_limit>
            <ci_upper_limit>0.156</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From screening visit (28 days before treatment start) until end of follow up period (up to 105 days).</time_frame>
      <desc>Safety analysis is reported for TS of both studies. Participants of each particular treatment arm in main and DH-study were combined in one particular treatment arm for adverse event reporting.</desc>
      <group_list>
        <group group_id="E1">
          <title>Tiotropium+Olodaterol (5μg/5μg)</title>
          <description>Once daily treatment of orally inhaled tiotropium + olodaterol (T+O) (5μg/5μg) fixed dose combination (FDC) over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients from Main and DH-study combined.</description>
        </group>
        <group group_id="E2">
          <title>Fluticasone Propionate+Salmeterol (500μg/100μg)</title>
          <description>Twice daily treatment of orally inhaled fluticasone propionate + salmeterol (F+S) (250μg/50μg) fixed dose combination (FDC) over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD). Patients from Main and DH-study combined.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 22.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="150"/>
              </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="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Stress cardiomyopathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Upper limb fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical spinal stenosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Intervertebral disc compression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Basal cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Squamous cell carcinoma of the oral cavity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="150"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 22.0</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="8" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="150"/>
              </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="8" subjects_at_risk="152"/>
                <counts group_id="E2" subjects_affected="15" subjects_at_risk="150"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

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


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03240575
org study id: 1237-0063
nct id: NCT03240575
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The primary objective of the trial is to show superiority in lung function of once daily (2
      inhalations) treatment with orally inhaled tiotropium+olodaterol fixed dose combination to
      twice daily (one inhalation) treatment with fluticasone propionate+salmeterol fixed dose
      combination over 12 weeks in patients with Chronic Obstructive Pulmonary Disease (COPD).

      A Digital Health (DH) exploratory study has been integrated into the main study as a site
      specific study. The DH exploratory study will be performed at a single site; the site is also
      participating in the main study. The DH exploratory study site will enter (randomize)
      approximately 20 patients (subjects) (in addition to the patients to be enrolled in the main
      study at this site). The patients enrolled in the DH exploratory study are not considered to
      be part of the main study (i.e. data collected in the DH exploratory study will be analyzed
      separately from the data collected in the main study).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 24 Hours (AUC0-24) Response (Change From Baseline) [L] After 12 Weeks of Treatment
time frame: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline.10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min, 12h 30 min, 13h, 14h, 22h, 23h, and 24h post morning dose at week 12.
description: Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 24 hours (AUC0-24) response (change from baseline) [L] after 12 weeks of treatment. FEV1 AUC0-24 was calculated as the area under the FEV1-time curve from 0-24 hours post-dose using the trapezoidal rule, divided by the duration (24 hours) and reported in liters. FEV1 AUC0-24 response (change from baseline) was defined as FEV1 AUC0-24 mius baseline FEV1.
measure: Forced Expiratory Volume in One Second (FEV1) Area Under the Curve From 0 to 12 Hours (AUC0-12) Response (Change From Baseline) [L] After 12 Weeks of Treatment
time frame: 1 hours (h) and 10 minutes (min) before first dose at day1 of weeks 1 for baseline. 10 min before and 30 min, 1 h, 2h, 3h, 4h, 6h, 8h, 10h, 11h 50min post morning dose at week 12.
description: Forced Expiratory Volume in one second (FEV1) Area under the Curve from 0 to 12 hours (AUC0-12) response (change from baseline) [L] after 12 weeks of treatment.
FEV1 AUC0-12 was calculated as the area under the FEV1-time curve from 0-12 hours post-dose using the trapezoidal rule, divided by the duration (12 hours) and reported in liters. FEV1 AUC0-12 response (change from baseline) was defined as FEV1 AUC0-12 minus baseline FEV1.
measure: Trough Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
time frame: At 23 h and 24 h post dose at baseline and at 23h and 24 h post dose at week 12.
description: Trough Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Trough FEV1 was defined as the mean of the FEV1 value measured at 23 hours and at 24 hours after the trial medication administration. Through FEV1 response (change from baseline) was defined as trough FEV1 minus baseline FEV1.
measure: Peak 0-3 Hours Forced Expiratory Volume in One Second (FEV1) Response (Change From Baseline) [L] After 12 Weeks Treatment
time frame: 30 minutes, 1 h, 2h and 3h post dose at baseline and week 12.
description: Peak 0-3 hours Forced Expiratory Volume in one second (FEV1) response (change from baseline) [L] after 12 weeks treatment. Peak 0-3h was defined as the maximum value measured within the first three hours post doing.
arm group label: Tiotropium + Olodaterol fixed dose combination
arm group type: Experimental
arm group label: Fluticasone propionate + Salmeterol fixed dose combination
arm group type: Active Comparator
intervention type: Drug
intervention name: Tiotropium
description: Fixed Dose Combination
arm group label: Tiotropium + Olodaterol fixed dose combination
other name: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO
intervention type: Drug
intervention name: Olodaterol
description: Fixed Dose Combination
arm group label: Tiotropium + Olodaterol fixed dose combination
other name: INSPIOLTO, SPIOLTO, STIOLTO, VAHELVA, YANIMO
intervention type: Drug
intervention name: Fluticasone propionate
description: Fixed Dose Combination
arm group label: Fluticasone propionate + Salmeterol fixed dose combination
intervention type: Drug
intervention name: Salmeterol
description: Fixed Dose Combination
arm group label: Fluticasone propionate + Salmeterol fixed dose combination
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
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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: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
mesh term: Fluticasone
mesh term: Xhance
mesh term: Tiotropium Bromide
mesh term: Salmeterol Xinafoate
mesh term: Olodaterol
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The objectives of the DH-study were exploratory. The DH-study aimed to gather information and experience about the feasibility of a remote trial in this indication, and was not designed to support treatment comparisons.
point of contact: 