<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/NCT02982187</url>
  </required_header>
  <id_info>
    <org_study_id>206215</org_study_id>
    <nct_id>NCT02982187</nct_id>
  </id_info>
  <brief_title>A Clinical Study Assessing Critical Errors, Training/Teaching Time, and Preference Attributes of the ELLIPTA® Dry Powder Inhaler, in Comparison to Combinations of Dry Powder Inhalers Used to Provide Triple Therapy, in Patients With Chronic Obstructive Pulmonary Disease</brief_title>
  <official_title>A Randomized, Open-label, Cross-over, Placebo-device Study Investigating Critical and Over All Errors, Training/Teaching Time, and Preference Attributes of the ELLIPTA Dry Powder Inhaler (DPI) as Compared to HANDIHALER DPI Used in Combination With Either DISKUS DPI or TURBUHALER DPI, in Adult Patients With Chronic Obstructive Pulmonary Disease (COPD)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>GlaxoSmithKline</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a randomized, multi-centre, open-label, placebo-device, cross-over study, with a 2x2&#xD;
      complete block design in subjects with chronic obstructive pulmonary disease (COPD) to assess&#xD;
      the benefits of delivering triple therapy using a single ELLIPTA dry powder inhaler (DPI)&#xD;
      (closed triple therapy) versus delivering triple therapy using two different types of DPI&#xD;
      (open triple therapy). The primary objective of the study is to evaluate the proportion of&#xD;
      COPD subjects who make critical errors when using a single ELLIPTA DPI versus those using&#xD;
      combinations of DISKUS® with HANDIHALER®, or TURBUHALER® with HANDIHALER. At Visit 1, all&#xD;
      subjects will demonstrate the use of ELLIPTA DPI, and HANDIHALER DPI in combination with&#xD;
      either DISKUS DPI (in sub-study 1) or TURBUHALER DPI (in sub-study 2), based on the treatment&#xD;
      sequences. At the end Visit 1, subjects will complete the inhaler preference questionnaire&#xD;
      (PQ). There is no active treatment and subjects will continue to take their own prescribed&#xD;
      COPD medication for the duration of the study. ELLIPTA and DISKUS are registered trademarks&#xD;
      of the GSK group of companies; TURBUHALER is a registered trademark of AstraZeneca and&#xD;
      HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH &amp; Co. KG.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 30, 2016</start_date>
  <completion_date type="Actual">June 19, 2017</completion_date>
  <primary_completion_date type="Actual">June 19, 2017</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>Crossover Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL)</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and critical errors made by the participants while using each DPI were recorded by the Healthcare Professional (HCP) on the checklists provided. Percentage of participants making at least one critical error after reading PIL were reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made errors while demonstrating DPI, HCP provided instruction on the correct use of the DPI. The participant then repeated the demonstration of DPI use, and the HCP recorded the critical errors made on the checklists. Percentage of participants making at least one critical error after the first instruction from the HCP were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made an error while demonstrating DPI use after first instruction from the HCP, then the HCP provided instructions again on the correct use of the inhaler. The participant then demonstrated the DPI for one last time, and the HCP recorded the critical errors made on the checklists. Participants making at least one critical error after the second instruction from the HCP were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Making at Least One Overall Error After Reading the PIL</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. Overall error was defined as an error including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL. For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after reading the PIL were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP</measure>
    <time_frame>Day 1</time_frame>
    <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the first instruction from the HCP were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP</measure>
    <time_frame>Day 1</time_frame>
    <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first, and second instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the second instruction from the HCP were reported. These statistics are only presented when the model has successfully converged.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use</measure>
    <time_frame>Day 1</time_frame>
    <description>In each sub-study, if the participant made error while demonstrating the use of the DPI after reading the PIL, the HCP demonstrated the correct usage instructions to the participant. The participant was then asked to demonstrate the DPI again. Any errors made were recorded by the HCP, and the same process was repeated one more time. In total, the HCP instructed the participants on the use of the DPI up to two times after which there were no assessment scheduled. Number of participants with instructions (0, 1 or 2) needed to demonstrate correct DPI use by the participants were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Median Time to Demonstrate Correct Inhaler Use (T1+T2)</measure>
    <time_frame>Day 1</time_frame>
    <description>For each DPI being tested, the total time taken from when participant started reading the PIL until when correct use was demonstrated (that is the time required to read PIL, and two attempts for correct use of DPI following instructions provided by the HCP ) was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1)</measure>
    <time_frame>Day 1</time_frame>
    <description>For each DPI being tested, the time taken from when participant started reading the PIL until when correct use was demonstrated with no need of instructions by HCP was reported. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time Taken to be Given Instruction by the HCP (up to 2 Times) on Use of the Inhaler and to Demonstrate Correct Inhaler Use (T2)</measure>
    <time_frame>Day 1</time_frame>
    <description>The time in minutes from when the HCP started to instruct participant for the correct use of DPI until correct use was demonstrated including maximum of two attempts only, was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. Participants who demonstrated correct use after reading the PIL (T1) were included with a time of 0 for T2. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored then the median is not applicable. Participants who demonstrated correct use after reading the PIL are included with T2=0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered the Number of Steps Required to Take the COPD Medication</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on the number of steps needed to take the COPD medication. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference</measure>
    <time_frame>Day 1</time_frame>
    <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on overall treatment preference. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
  </secondary_outcome>
  <number_of_arms>8</number_of_arms>
  <enrollment type="Actual">160</enrollment>
  <condition>Pulmonary Disease, Chronic Obstructive</condition>
  <arm_group>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then DISKUS + HANDIHALER in period 2. At the end of Visit 1, subjects will complete version 1 of the PQ (PQ1)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use DISKUS + HANDIHALER in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete version 2 of the PQ (PQ2)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then DISKUS + HANDIHALER in period 2. At the end of Visit 1, subjects will complete PQ2</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use DISKUS + HANDIHALER in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete PQ1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then TURBUHALER + HANDIHALER in period 2. At the end of Visit 1, subjects will complete version 3 of the PQ (PQ3)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use TURBUHALER + HANDIHALER inhaler in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete version 4 of the PQ (PQ4)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then TURBUHALER + HANDIHALER in period 2. At the end of Visit 1, subjects will complete PQ4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In this sequence, subjects will be randomized to use TURBUHALER + HANDIHALER inhaler in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete PQ3</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo ELLIPTA</intervention_name>
    <description>It is a dry powder inhaler device that can hold two individual blisters: one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.</description>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2</arm_group_label>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3</arm_group_label>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo DISKUS</intervention_name>
    <description>It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.</description>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo TURBUHALER</intervention_name>
    <description>It is a placebo dry powder inhaler containing lactose monohydrate.</description>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3</arm_group_label>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo HANDIHALER</intervention_name>
    <description>Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.</description>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2</arm_group_label>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3</arm_group_label>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PQ1</intervention_name>
    <description>Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions, but differ in the ordering of inhalers in their responses.</description>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PQ2</intervention_name>
    <description>Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.</description>
    <arm_group_label>Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2</arm_group_label>
    <arm_group_label>Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PQ3</intervention_name>
    <description>Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.</description>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>PQ4</intervention_name>
    <description>Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.</description>
    <arm_group_label>Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4</arm_group_label>
    <arm_group_label>Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Age &gt;=40 years at Visit 1&#xD;
&#xD;
          -  Diagnosis of COPD with a documented history of COPD, in accordance with the definition&#xD;
             by the European Respiratory Society.&#xD;
&#xD;
          -  Current COPD Therapy: Currently receiving maintenance therapy with a fixed dose&#xD;
             combination of a long-acting beta 2-agonist (LABA) and inhaled corticosteroid (ICS).&#xD;
             Subject may also be receiving long-acting muscarinic antagonist (LAMA; also known as a&#xD;
             long-acting anti-cholinergic). Subjects must be able to continue using their currently&#xD;
             prescribed COPD maintenance inhaler therapy throughout the study and as needed short&#xD;
             acting beta-adrenergic agonist (SABA) and/or short acting muscarinic antagonist (SAMA)&#xD;
             for rescue use.&#xD;
&#xD;
          -  Has been on current maintenance ICS/LABA COPD treatment for at least 4 weeks prior to&#xD;
             V0 and evaluated as unlikely to change treatment within 4 weeks of Visit 1.&#xD;
&#xD;
          -  Current or former (defined as subjects who have quit smoking for at least 3 months&#xD;
             prior to V0/V1) cigarette smokers with a &gt;10 pack-year smoking history (Number of pack&#xD;
             years=[number of cigarettes per day ÷ 20] x number of years smoked [e.g., 10&#xD;
             pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day&#xD;
             for 20 years]).&#xD;
&#xD;
          -  Males or females who are not pregnant or not planning a pregnancy during the study or&#xD;
             not lactating&#xD;
&#xD;
          -  Capable of giving signed informed consent which includes compliance with the&#xD;
             requirements and restrictions listed in the informed consent form (ICF) and in this&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          -  Subjects with a current diagnosis of asthma. Subjects with a prior history of asthma&#xD;
             are eligible if they have a current diagnosis of COPD.&#xD;
&#xD;
          -  Subjects who used any ELLIPTA inhaler (participated in a clinical study of GW685698,&#xD;
             GW642444, GSK573719 [fluticasone furoate, vilanterol, umeclidinium bromide], or any&#xD;
             combination thereof, or placebo in an ELLIPTA inhaler study) within 24 months prior to&#xD;
             Visit 0.&#xD;
&#xD;
          -  Subjects who used any capsule system inhaler (e.g. Spiriva HANDIHALER,&#xD;
             SEEBRI®/ULTIBRO® BREEZHALER®, or participated in a clinical studies of these,&#xD;
             including placebo inhalers) within 24 months prior to Visit 0. SEEBRI, ULTIBRO, and&#xD;
             BREEZHALER are registered trademarks of Novartis AG.&#xD;
&#xD;
          -  Dependent on which sub-study a subject is included on they should not have any recent&#xD;
             experience, within 24 months of V 0 of the following inhaler for the sub study&#xD;
             included on: Sub Study 1: DISKUS inhaler (e.g., Seretide DISKUS or placebo DISKUS) and&#xD;
             Sub Study 2:TURBUHALER (e.g. Symbicort TURBUHALER or placebo TURBUHALER)&#xD;
&#xD;
          -  Subjects with a known or suspected alcohol or drug abuse at Visit 1 which in the&#xD;
             opinion of the investigator could interfere with the subject's proper completion of&#xD;
             the protocol requirement&#xD;
&#xD;
          -  A history of hypersensitivity to any components of the study inhaler (e.g., lactose,&#xD;
             magnesium stearate). In addition, subjects with a history of severe milk protein&#xD;
             allergy that, in the opinion of the study physician, contraindicates participation&#xD;
             will also be excluded.&#xD;
&#xD;
          -  Subjects who have received an investigational drug and/or medical device within 30&#xD;
             days of entry into this study (Screening/Visit 1), or within five drug half-lives of&#xD;
             the investigational drug, whichever is longer&#xD;
&#xD;
          -  In the opinion of the investigator, any subject who is unable to read and/or would not&#xD;
             be able to complete a questionnaire and understand verbal instructions.&#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>GSK Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>GlaxoSmithKline</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Enschede</city>
        <zip>7513 ER</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Nijverdal</city>
        <zip>7442 LS</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>Rotterdam</city>
        <zip>3051 GV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>London</city>
        <zip>EC1M 6BQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GSK Investigational Site</name>
      <address>
        <city>London</city>
        <zip>NW10 7EW</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>van der Palen J, Moeskops-van Beurden W, Dawson CM, James WY, Preece A, Midwinter D, Barnes N, Sharma R. A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018 Aug 21;13:2515-2523. doi: 10.2147/COPD.S169060. eCollection 2018.</citation>
    <PMID>30174421</PMID>
  </reference>
  <verification_date>September 2019</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 1, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 5, 2016</study_first_posted>
  <results_first_submitted>June 11, 2018</results_first_submitted>
  <results_first_submitted_qc>September 27, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 21, 2019</results_first_posted>
  <last_update_submitted>September 27, 2019</last_update_submitted>
  <last_update_submitted_qc>September 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 21, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HANDIHALER</keyword>
  <keyword>ELLIPTA</keyword>
  <keyword>TURBUHALER</keyword>
  <keyword>DISKUS</keyword>
  <keyword>COPD</keyword>
  <keyword>critical error</keyword>
  <keyword>inhaler preference</keyword>
  <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>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>July 18, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02982187/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>September 15, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT02982187/Prot_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>This is a randomized, multi-center, open-label, cross-over study comparing Placebo ELLIPTA Dry Power Inhaler (DPI) with either Placebo DISKUS DPI + Placebo Handihaler or Placebo Turbuhaler plus Placebo Handihaler to assess correct inhaler use. A total of 5 centers, 3 in the Netherlands and 2 in the United Kingdom participated in the study.</recruitment_details>
      <pre_assignment_details>A total of 160 participants were screened. Eighty were assigned to sub-study 1 and 80 to sub-study 2 according to naivety to inhalers in each sub-study. One participant in sub-study 2 withdrew consent prior to device assessment. Therefore 80 par in sub-study 1 and 79 par in sub-study 2 are included in the intent to treat population.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>ELLIPTA/DISKUS+HandiHaler/Q1</title>
          <description>Participants received placebo via ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by preference questionnaire (PQ) 1. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P2">
          <title>ELLIPTA/DISKUS+HandiHaler/Q2</title>
          <description>Participants received placebo via ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P3">
          <title>DISKUS+HandiHaler/ELLIPTA/Q1</title>
          <description>Participants received placebo via DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1 respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P4">
          <title>DISKUS+HandiHaler/ELLIPTA/Q2</title>
          <description>Participants received placebo via DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ2. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P5">
          <title>ELLIPTA/Turbuhaler+HandiHaler/Q3</title>
          <description>Participants received placebo via ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ3. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P6">
          <title>ELLIPTA/Turbuhaler+HandiHaler/Q4</title>
          <description>Participants received placebo via ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ4. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P7">
          <title>Turbuhaler+HandiHaler/ELLIPTA/Q3</title>
          <description>Participants received placebo via Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ3. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="P8">
          <title>Turbuhaler+HandiHaler/ELLIPTA/Q4</title>
          <description>Participants received placebo via Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ4. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the 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="20"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="20"/>
                <participants group_id="P6" count="20"/>
                <participants group_id="P7" count="20"/>
                <participants group_id="P8" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
                <participants group_id="P2" count="20"/>
                <participants group_id="P3" count="20"/>
                <participants group_id="P4" count="20"/>
                <participants group_id="P5" count="20"/>
                <participants group_id="P6" count="20"/>
                <participants group_id="P7" count="19"/>
                <participants group_id="P8" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
                <participants group_id="P7" count="1"/>
                <participants group_id="P8" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Intent-to-Treat Population comprised of all randomized participants who made at least one critical error assessment from one treatment option device. One participant withdrew consent prior to device assessment in Sub-study 2 and only 79 participants were included in Intent-to-Treat Population.</population>
      <group_list>
        <group group_id="B1">
          <title>Sub Study 1: ELLIPTA vs DISKUS + HandiHaler</title>
          <description>Participants received placebo via one of the following devices: ELLIPTA® DPI or DISKUS® DPI in combination with HANDIHALER® DPI based on the following four sequences. The sequences also include the preference questionnaire version: A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2,followed by PQ1), B (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2,followed by PQ2), C (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2), D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="B2">
          <title>Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler</title>
          <description>Participants received placebo via one of the following devices: ELLIPTA DPI or TURBUHALER® DPI in combination with HANDIHALER DPI based on the following four sequences. The sequences also include the preference questionnaire version: : E (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ3), F (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ4), G (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ4), H (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ3) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</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="80"/>
            <count group_id="B2" value="79"/>
            <count group_id="B3" value="159"/>
          </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="64.3" spread="8.69"/>
                    <measurement group_id="B2" value="65.7" spread="8.49"/>
                    <measurement group_id="B3" value="65.0" spread="8.60"/>
                  </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="39"/>
                    <measurement group_id="B2" value="37"/>
                    <measurement group_id="B3" value="76"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="41"/>
                    <measurement group_id="B2" value="42"/>
                    <measurement group_id="B3" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>African American/African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - Central/South Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Asian - South East Asian Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - Arabic/North African Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White - White/Caucasian/European Heritage</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="55"/>
                    <measurement group_id="B3" value="108"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL)</title>
        <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and critical errors made by the participants while using each DPI were recorded by the Healthcare Professional (HCP) on the checklists provided. Percentage of participants making at least one critical error after reading PIL were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL)</title>
          <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and critical errors made by the participants while using each DPI were recorded by the Healthcare Professional (HCP) on the checklists provided. Percentage of participants making at least one critical error after reading PIL were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="75"/>
                    <measurement group_id="O3" value="9"/>
                    <measurement group_id="O4" value="73"/>
                  </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>Sub study 1: DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>29.114</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>11.047</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>27.744</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>10.512</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP</title>
        <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made errors while demonstrating DPI, HCP provided instruction on the correct use of the DPI. The participant then repeated the demonstration of DPI use, and the HCP recorded the critical errors made on the checklists. Percentage of participants making at least one critical error after the first instruction from the HCP were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP</title>
          <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made errors while demonstrating DPI, HCP provided instruction on the correct use of the DPI. The participant then repeated the demonstration of DPI use, and the HCP recorded the critical errors made on the checklists. Percentage of participants making at least one critical error after the first instruction from the HCP were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="14"/>
                  </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>Sub study 1:DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.029</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>4.248</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.416</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.026</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.855</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.394</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP</title>
        <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made an error while demonstrating DPI use after first instruction from the HCP, then the HCP provided instructions again on the correct use of the inhaler. The participant then demonstrated the DPI for one last time, and the HCP recorded the critical errors made on the checklists. Participants making at least one critical error after the second instruction from the HCP were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP</title>
          <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made an error while demonstrating DPI use after first instruction from the HCP, then the HCP provided instructions again on the correct use of the inhaler. The participant then demonstrated the DPI for one last time, and the HCP recorded the critical errors made on the checklists. Participants making at least one critical error after the second instruction from the HCP were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="5"/>
                  </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>Sub study 1:DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.400</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.000</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.459</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.500</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.732</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.397</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Making at Least One Overall Error After Reading the PIL</title>
        <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. Overall error was defined as an error including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL. For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after reading the PIL were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Overall Error After Reading the PIL</title>
          <description>Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. Overall error was defined as an error including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL. For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after reading the PIL were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="80"/>
                    <measurement group_id="O3" value="22"/>
                    <measurement group_id="O4" value="80"/>
                  </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>Sub study 1:DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>24.539</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>9.268</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>17.974</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>7.239</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP</title>
        <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the first instruction from the HCP were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP</title>
          <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the first instruction from the HCP were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="5"/>
                    <measurement group_id="O4" value="20"/>
                  </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>Sub study 1:DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.067</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>3.237</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>1.124</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.003</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>6.357</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>2.219</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP</title>
        <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first, and second instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the second instruction from the HCP were reported. These statistics are only presented when the model has successfully converged.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP</title>
          <description>For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first, and second instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the second instruction from the HCP were reported. These statistics are only presented when the model has successfully converged.</description>
          <population>Intent-to-Treat Population</population>
          <units>Percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="6"/>
                  </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>Sub study 1: DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <other_analysis_desc>These statistics were only presented when the model successfully converged. A stratified exact logistic model was used with participant included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</other_analysis_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.500</p_value>
            <method>stratified exact logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.732</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.397</ci_lower_limit>
            <ci_upper_limit_na_comment>The upper bound of the 95% CI could not be calculated due to the low number of events and is therefore displayed as NA.</ci_upper_limit_na_comment>
            <estimate_desc>Odds ratio, 95% CI and P-value obtained from a stratified exact logistic model. Participant is included in the model as fixed strata, treatment option in the exact statement and period included as a fixed effect.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use</title>
        <description>In each sub-study, if the participant made error while demonstrating the use of the DPI after reading the PIL, the HCP demonstrated the correct usage instructions to the participant. The participant was then asked to demonstrate the DPI again. Any errors made were recorded by the HCP, and the same process was repeated one more time. In total, the HCP instructed the participants on the use of the DPI up to two times after which there were no assessment scheduled. Number of participants with instructions (0, 1 or 2) needed to demonstrate correct DPI use by the participants were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use</title>
          <description>In each sub-study, if the participant made error while demonstrating the use of the DPI after reading the PIL, the HCP demonstrated the correct usage instructions to the participant. The participant was then asked to demonstrate the DPI again. Any errors made were recorded by the HCP, and the same process was repeated one more time. In total, the HCP instructed the participants on the use of the DPI up to two times after which there were no assessment scheduled. Number of participants with instructions (0, 1 or 2) needed to demonstrate correct DPI use by the participants were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Number of Instructions, 0</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="61"/>
                    <measurement group_id="O2" value="16"/>
                    <measurement group_id="O3" value="62"/>
                    <measurement group_id="O4" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Instructions, 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="15"/>
                    <measurement group_id="O2" value="52"/>
                    <measurement group_id="O3" value="13"/>
                    <measurement group_id="O4" value="47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Number of Instructions, 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="3"/>
                    <measurement group_id="O4" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Failed to demonstrate correct use</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="6"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="5"/>
                  </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>Sub study 1:DISKUS + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon signed rank test</method>
            <method_desc>This method of analysis does not take sequence of treatment option into account</method_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O3</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Sub study 2:Turbuhaler + HandiHaler vs ELLIPTA</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Wilcoxon signed rank test</method>
            <method_desc>This method of analysis does not take sequence of treatment option into account</method_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>The Median Time to Demonstrate Correct Inhaler Use (T1+T2)</title>
        <description>For each DPI being tested, the total time taken from when participant started reading the PIL until when correct use was demonstrated (that is the time required to read PIL, and two attempts for correct use of DPI following instructions provided by the HCP ) was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>The Median Time to Demonstrate Correct Inhaler Use (T1+T2)</title>
          <description>For each DPI being tested, the total time taken from when participant started reading the PIL until when correct use was demonstrated (that is the time required to read PIL, and two attempts for correct use of DPI following instructions provided by the HCP ) was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
          <population>Intent-to-Treat Population.</population>
          <units>Minutes</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.68" lower_limit="0.8" upper_limit="12.9"/>
                    <measurement group_id="O2" value="10.57" lower_limit="1.5" upper_limit="42.4"/>
                    <measurement group_id="O3" value="2.58" lower_limit="0.7" upper_limit="25.2"/>
                    <measurement group_id="O4" value="11.30" lower_limit="3.3" upper_limit="55.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1)</title>
        <description>For each DPI being tested, the time taken from when participant started reading the PIL until when correct use was demonstrated with no need of instructions by HCP was reported. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population..</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1)</title>
          <description>For each DPI being tested, the time taken from when participant started reading the PIL until when correct use was demonstrated with no need of instructions by HCP was reported. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.</description>
          <population>Intent-to-Treat Population..</population>
          <units>Minutes</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.88" lower_limit="0.8" upper_limit="7.2"/>
                    <measurement group_id="O2" value="NA" lower_limit="1.5" upper_limit="19.2">&gt;50% of participants were censored; therefore the median is not applicable.</measurement>
                    <measurement group_id="O3" value="2.78" lower_limit="0.7" upper_limit="8.6"/>
                    <measurement group_id="O4" value="NA" lower_limit="3.3" upper_limit="15.1">&gt;50% of participants were censored; therefore the median is not applicable.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time Taken to be Given Instruction by the HCP (up to 2 Times) on Use of the Inhaler and to Demonstrate Correct Inhaler Use (T2)</title>
        <description>The time in minutes from when the HCP started to instruct participant for the correct use of DPI until correct use was demonstrated including maximum of two attempts only, was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. Participants who demonstrated correct use after reading the PIL (T1) were included with a time of 0 for T2. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored then the median is not applicable. Participants who demonstrated correct use after reading the PIL are included with T2=0.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population.</population>
        <group_list>
          <group group_id="O1">
            <title>Sub-study 1 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in either period 1 or 2.</description>
          </group>
          <group group_id="O2">
            <title>Sub-study 1 : DISKUS + HandiHaler</title>
            <description>Participants were randomized to use placebo via DISKUS + HANDIHALER in period 1 or 2.</description>
          </group>
          <group group_id="O3">
            <title>Sub-study 2 : ELLIPTA</title>
            <description>Participants were randomized to use placebo via ELLIPTA in period 1 or 2.</description>
          </group>
          <group group_id="O4">
            <title>Sub-study 2 : Turbuhaler + HandiHaler</title>
            <description>Participants were randomized to use placebo via TURBUHALER + HANDIHALER in period 1 or 2.</description>
          </group>
        </group_list>
        <measure>
          <title>Time Taken to be Given Instruction by the HCP (up to 2 Times) on Use of the Inhaler and to Demonstrate Correct Inhaler Use (T2)</title>
          <description>The time in minutes from when the HCP started to instruct participant for the correct use of DPI until correct use was demonstrated including maximum of two attempts only, was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. Participants who demonstrated correct use after reading the PIL (T1) were included with a time of 0 for T2. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored then the median is not applicable. Participants who demonstrated correct use after reading the PIL are included with T2=0.</description>
          <population>Intent-to-Treat Population.</population>
          <units>Minutes</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="80"/>
                <count group_id="O3" value="79"/>
                <count group_id="O4" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.00" lower_limit="0.0" upper_limit="3.3"/>
                    <measurement group_id="O2" value="2.89" lower_limit="0.0" upper_limit="16.5"/>
                    <measurement group_id="O3" value="0.00" lower_limit="0.0" upper_limit="6.3"/>
                    <measurement group_id="O4" value="3.12" lower_limit="0.0" upper_limit="14.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered the Number of Steps Required to Take the COPD Medication</title>
        <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on the number of steps needed to take the COPD medication. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub Study 1: ELLIPTA vs DISKUS + HandiHaler</title>
            <description>Participants received placebo via one of the following devices: ELLIPTA® DPI or DISKUS® DPI in combination with HANDIHALER® DPI based on the following four sequences. The sequences also include the preference questionnaire version: A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2,followed by PQ1), B (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2,followed by PQ2), C (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2), D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler</title>
            <description>Participants received placebo via one of the following devices: ELLIPTA DPI or TURBUHALER® DPI in combination with HANDIHALER DPI based on the following four sequences. The sequences also include the preference questionnaire version: : E (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ3), F (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ4), G (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ4), H (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ3) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered the Number of Steps Required to Take the COPD Medication</title>
          <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on the number of steps needed to take the COPD medication. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ELLIPTA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="71"/>
                    <measurement group_id="O2" value="72"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DISKUS + HandiHaler</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No Preference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference</title>
        <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on overall treatment preference. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
        <time_frame>Day 1</time_frame>
        <population>Intent-to-Treat Population</population>
        <group_list>
          <group group_id="O1">
            <title>Sub Study 1: ELLIPTA vs DISKUS + HandiHaler</title>
            <description>Participants received placebo via one of the following devices: ELLIPTA® DPI or DISKUS® DPI in combination with HANDIHALER® DPI based on the following four sequences. The sequences also include the preference questionnaire version: A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2,followed by PQ1), B (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2,followed by PQ2), C (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2), D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
          </group>
          <group group_id="O2">
            <title>Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler</title>
            <description>Participants received placebo via one of the following devices: ELLIPTA DPI or TURBUHALER® DPI in combination with HANDIHALER DPI based on the following four sequences. The sequences also include the preference questionnaire version: : E (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ3), F (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ4), G (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ4), H (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ3) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference</title>
          <description>Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on overall treatment preference. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.</description>
          <population>Intent-to-Treat Population</population>
          <units>Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="79"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>ELLIPTA</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65"/>
                    <measurement group_id="O2" value="66"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>DISKUS + HandiHaler</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>No Preference</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Cochran-Mantel-Haenszel</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Day 1</time_frame>
      <desc>Intent-to-Treat Population was used to collect Adverse Events. Since all participants received placebo as treatment, data has been clubbed for all the arms. No Serious Adverse Events or deaths were reported during this study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Sub Study 1: ELLIPTA vs DISKUS + HandiHaler</title>
          <description>Participants received placebo via one of the following devices: ELLIPTA® DPI or DISKUS® DPI in combination with HANDIHALER® DPI based on the following four sequences. The sequences also include the preference questionnaire version: A (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2,followed by PQ1), B (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2,followed by PQ2), C (ELLIPTA in period 1 and DISKUS + HandiHaler in period 2, followed by PQ2), D (DISKUS + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ1) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
        <group group_id="E2">
          <title>Sub Study 2: ELLIPTA vs Turbuhaler + HandiHaler</title>
          <description>Participants received placebo via one of the following devices: ELLIPTA DPI or TURBUHALER® DPI in combination with HANDIHALER DPI based on the following four sequences. The sequences also include the preference questionnaire version: : E (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ3), F (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ4), G (ELLIPTA in period 1 and Turbuhaler + HandiHaler in period 2, followed by PQ4), H (Turbuhaler + HandiHaler in period 1 and ELLIPTA in period 2, followed by PQ3) respectively. There was no active treatment and participants continued to take their own prescribed COPD medication for the duration of the study.</description>
        </group>
      </group_list>
      <serious_events>
        <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="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA</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="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Laceration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="80"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="79"/>
              </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>GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>GSK Response Center</name_or_title>
      <organization>GlaxoSmithKline</organization>
      <phone>866-435-7343</phone>
      <email>GSKClinicalSupportHD@gsk.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/NCT02982187
org study id: 206215
nct id: NCT02982187
lead sponsor: 
has dmc: No
This is a randomized, multi-centre, open-label, placebo-device, cross-over study, with a 2x2
      complete block design in subjects with chronic obstructive pulmonary disease (COPD) to assess
      the benefits of delivering triple therapy using a single ELLIPTA dry powder inhaler (DPI)
      (closed triple therapy) versus delivering triple therapy using two different types of DPI
      (open triple therapy). The primary objective of the study is to evaluate the proportion of
      COPD subjects who make critical errors when using a single ELLIPTA DPI versus those using
      combinations of DISKUS® with HANDIHALER®, or TURBUHALER® with HANDIHALER. At Visit 1, all
      subjects will demonstrate the use of ELLIPTA DPI, and HANDIHALER DPI in combination with
      either DISKUS DPI (in sub-study 1) or TURBUHALER DPI (in sub-study 2), based on the treatment
      sequences. At the end Visit 1, subjects will complete the inhaler preference questionnaire
      (PQ). There is no active treatment and subjects will continue to take their own prescribed
      COPD medication for the duration of the study. ELLIPTA and DISKUS are registered trademarks
      of the GSK group of companies; TURBUHALER is a registered trademark of AstraZeneca and
      HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL)
time frame: Day 1
description: Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and critical errors made by the participants while using each DPI were recorded by the Healthcare Professional (HCP) on the checklists provided. Percentage of participants making at least one critical error after reading PIL were reported.
measure: Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP
time frame: Day 1
description: Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made errors while demonstrating DPI, HCP provided instruction on the correct use of the DPI. The participant then repeated the demonstration of DPI use, and the HCP recorded the critical errors made on the checklists. Percentage of participants making at least one critical error after the first instruction from the HCP were reported.
measure: Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP
time frame: Day 1
description: Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. A critical error was defined as an error that was most likely to result in no, or a significantly reduced amount, of medication being inhaled by the participant. After reading the PIL for each DPI to be tested, participants demonstrated the DPI and errors made by the participants while using each DPI were recorded by the HCP on the checklists provided. If a participant made an error while demonstrating DPI use after first instruction from the HCP, then the HCP provided instructions again on the correct use of the inhaler. The participant then demonstrated the DPI for one last time, and the HCP recorded the critical errors made on the checklists. Participants making at least one critical error after the second instruction from the HCP were reported.
measure: Percentage of Participants Making at Least One Overall Error After Reading the PIL
time frame: Day 1
description: Participants were provided with the relevant section of the PIL, explaining correct use, for each DPI they were to be tested on. Overall error was defined as an error including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL. For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after reading the PIL were reported.
measure: Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP
time frame: Day 1
description: For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the first instruction from the HCP were reported.
measure: Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP
time frame: Day 1
description: For each DPI to be tested, overall errors including critical and non-critical errors made by the participants while demonstrating DPI use after reading the PIL following first, and second instruction from the HCP were recorded by the HCP on the checklists provided. Percentage of participants making at least one overall error after the second instruction from the HCP were reported. These statistics are only presented when the model has successfully converged.
measure: Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use
time frame: Day 1
description: In each sub-study, if the participant made error while demonstrating the use of the DPI after reading the PIL, the HCP demonstrated the correct usage instructions to the participant. The participant was then asked to demonstrate the DPI again. Any errors made were recorded by the HCP, and the same process was repeated one more time. In total, the HCP instructed the participants on the use of the DPI up to two times after which there were no assessment scheduled. Number of participants with instructions (0, 1 or 2) needed to demonstrate correct DPI use by the participants were reported.
measure: The Median Time to Demonstrate Correct Inhaler Use (T1+T2)
time frame: Day 1
description: For each DPI being tested, the total time taken from when participant started reading the PIL until when correct use was demonstrated (that is the time required to read PIL, and two attempts for correct use of DPI following instructions provided by the HCP ) was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.
measure: Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1)
time frame: Day 1
description: For each DPI being tested, the time taken from when participant started reading the PIL until when correct use was demonstrated with no need of instructions by HCP was reported. A participant who did not demonstrate correct use at the end of the time period was censored. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored therefore the median is not applicable.
measure: Time Taken to be Given Instruction by the HCP (up to 2 Times) on Use of the Inhaler and to Demonstrate Correct Inhaler Use (T2)
time frame: Day 1
description: The time in minutes from when the HCP started to instruct participant for the correct use of DPI until correct use was demonstrated including maximum of two attempts only, was recorded. A participant who did not demonstrate correct use at the end of the time period was censored. Participants who demonstrated correct use after reading the PIL (T1) were included with a time of 0 for T2. The median time to demonstrate correct DPI use (minutes) is taken from the Kaplan-Meier analysis. If more than 50% of the data is censored then the median is not applicable. Participants who demonstrated correct use after reading the PIL are included with T2=0.
measure: Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered the Number of Steps Required to Take the COPD Medication
time frame: Day 1
description: Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on the number of steps needed to take the COPD medication. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.
measure: Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference
time frame: Day 1
description: Participants demonstrated the use of ELLIPTA, and depending on the substudy DISKUS plus HandiHaler or Turbuhaler plus Handihaler. At the end of Visit 1, participants completed specific versions of the inhaler PQ (PQ1, PQ2, PQ3 or PQ4) according to the questionnaire they were randomized to. Participants assessed the inhaler preference based on overall treatment preference. Participants checked the response from the choice of ELLIPTA, DISKUS + HandiHaler (sub-study 1), Turbuhaler + Handihaler (sub-study 2) and No Preference. Number of participants with treatment preference based on responses to the preference questionnaire were reported.
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1
arm group type: Experimental
description: In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then DISKUS + HANDIHALER in period 2. At the end of Visit 1, subjects will complete version 1 of the PQ (PQ1)
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2
arm group type: Experimental
description: In this sequence, subjects will be randomized to use DISKUS + HANDIHALER in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete version 2 of the PQ (PQ2)
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2
arm group type: Experimental
description: In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then DISKUS + HANDIHALER in period 2. At the end of Visit 1, subjects will complete PQ2
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1
arm group type: Experimental
description: In this sequence, subjects will be randomized to use DISKUS + HANDIHALER in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete PQ1
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3
arm group type: Experimental
description: In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then TURBUHALER + HANDIHALER in period 2. At the end of Visit 1, subjects will complete version 3 of the PQ (PQ3)
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4
arm group type: Experimental
description: In this sequence, subjects will be randomized to use TURBUHALER + HANDIHALER inhaler in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete version 4 of the PQ (PQ4)
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4
arm group type: Experimental
description: In this sequence, subjects will be randomized to use ELLIPTA inhaler in period 1 and then TURBUHALER + HANDIHALER in period 2. At the end of Visit 1, subjects will complete PQ4
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3
arm group type: Experimental
description: In this sequence, subjects will be randomized to use TURBUHALER + HANDIHALER inhaler in period 1 and then ELLIPTA in period 2. At the end of Visit 1, subjects will complete PQ3
intervention type: Device
intervention name: Placebo ELLIPTA
description: It is a dry powder inhaler device that can hold two individual blisters: one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4
intervention type: Device
intervention name: Placebo DISKUS
description: It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2
intervention type: Device
intervention name: Placebo TURBUHALER
description: It is a placebo dry powder inhaler containing lactose monohydrate.
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4
intervention type: Device
intervention name: Placebo HANDIHALER
description: Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4
intervention type: Other
intervention name: PQ1
description: Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions, but differ in the ordering of inhalers in their responses.
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1
intervention type: Other
intervention name: PQ2
description: Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.
arm group label: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2
arm group label: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2
intervention type: Other
intervention name: PQ3
description: Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3
intervention type: Other
intervention name: PQ4
description: Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.
arm group label: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4
arm group label: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4
criteria: 
gender: All
minimum age: 40 Years
maximum age: N/A
healthy volunteers: No
last name: GSK Clinical Trials
role: Study Director
affiliation: GlaxoSmithKline
facility: 
facility: 
facility: 
facility: 
facility: 
country: Netherlands
country: United Kingdom
citation: van der Palen J, Moeskops-van Beurden W, Dawson CM, James WY, Preece A, Midwinter D, Barnes N, Sharma R. A randomized, open-label, single-visit, crossover study simulating triple-drug delivery with Ellipta compared with dual inhaler combinations in patients with COPD. Int J Chron Obstruct Pulmon Dis. 2018 Aug 21;13:2515-2523. doi: 10.2147/COPD.S169060. eCollection 2018.
PMID: 30174421
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Lung Diseases, Obstructive
mesh term: Pulmonary Disease, Chronic Obstructive
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 