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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Device: Placebo ELLIPTA
* Device: Placebo DISKUS
* Device: Placebo TURBUHALER
* Device: Placebo HANDIHALER
* Other: PQ1
* Other: PQ2
* Other: PQ3
* Other: PQ4


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age >=40 years at Visit 1 Diagnosis of COPD with a documented history of COPD, in accordance with the definition by the European Respiratory Society. Current COPD Therapy: Currently receiving maintenance therapy with a fixed dose combination of a long-acting beta 2-agonist (LABA) and inhaled corticosteroid (ICS). Subject may also be receiving long-acting muscarinic antagonist (LAMA; also known as a long-acting anti-cholinergic). Subjects must be able to continue using their currently prescribed COPD maintenance inhaler therapy throughout the study and as needed short acting beta-adrenergic agonist (SABA) and/or short acting muscarinic antagonist (SAMA) for rescue use. Has been on current maintenance ICS/LABA COPD treatment for at least 4 weeks prior to V0 and evaluated as unlikely to change treatment within 4 weeks of Visit 1. Current or former (defined as subjects who have quit smoking for at least 3 months prior to V0/V1) cigarette smokers with a >10 pack-year smoking history (Number of pack years=[number of cigarettes per day ÷ 20] x number of years smoked [e.g., 10 pack-years is equal to 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years]). Males or females who are not pregnant or not planning a pregnancy during the study or not lactating Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol. Exclusion Criteria Subjects with a current diagnosis of asthma. Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD. Subjects who used any ELLIPTA inhaler (participated in a clinical study of GW685698, GW642444, GSK573719 [fluticasone furoate, vilanterol, umeclidinium bromide], or any combination thereof, or placebo in an ELLIPTA inhaler study) within 24 months prior to Visit 0. Subjects who used any capsule system inhaler (e.g. Spiriva HANDIHALER, SEEBRI®/ULTIBRO® BREEZHALER®, or participated in a clinical studies of these, including placebo inhalers) within 24 months prior to Visit 0. SEEBRI, ULTIBRO, and BREEZHALER are registered trademarks of Novartis AG. Dependent on which sub-study a subject is included on they should not have any recent experience, within 24 months of V 0 of the following inhaler for the sub study included on: Sub Study 1: DISKUS inhaler (e.g., Seretide DISKUS or placebo DISKUS) and Sub Study 2:TURBUHALER (e.g. Symbicort TURBUHALER or placebo TURBUHALER) Subjects with a known or suspected alcohol or drug abuse at Visit 1 which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement A history of hypersensitivity to any components of the study inhaler (e.g., lactose, magnesium stearate). In addition, subjects with a history of severe milk protein allergy that, in the opinion of the study physician, contraindicates participation will also be excluded. Subjects who have received an investigational drug and/or medical device within 30 days of entry into this study (Screening/Visit 1), or within five drug half-lives of the investigational drug, whichever is longer In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete a questionnaire and understand verbal instructions.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ1<br>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) | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo DISKUS<br>* It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ1<br>* 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.<br>|
| Experimental: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ2<br>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) | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo DISKUS<br>* It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ2<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|
| Experimental: Sub-study 1 : ELLIPTA followed by DISKUS+ HANDIHALER +PQ2<br>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 | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo DISKUS<br>* It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ2<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|
| Experimental: Sub-study 1 : DISKUS + HANDIHALER followed by ELLIPTA+PQ1<br>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 | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo DISKUS<br>* It is a placebo dry powder inhaler with one blister strip containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ1<br>* 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.<br>|
| Experimental: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ3<br>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) | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo TURBUHALER<br>* It is a placebo dry powder inhaler containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ3<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|
| Experimental: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ4<br>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) | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo TURBUHALER<br>* It is a placebo dry powder inhaler containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ4<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|
| Experimental: Substudy 2: ELLIPTA followed by TURBUHALER + HANDIHALER +PQ4<br>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 | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo TURBUHALER<br>* It is a placebo dry powder inhaler containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ4<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|
| Experimental: Substudy 2: TURBUHALER + HANDIHALER followed by ELLIPTA+PQ3<br>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 | Device: Placebo ELLIPTA<br>* 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.<br>Device: Placebo TURBUHALER<br>* It is a placebo dry powder inhaler containing lactose monohydrate.<br>Device: Placebo HANDIHALER<br>* Placebo capsules contain lactose monohydrate in the form of powder for oral inhalation, to be used with HANDIHALER device.<br>Other: PQ3<br>* Consists of 2 questions to assess subjects' preference of device attributes and dosing regimens. The 4 versions of the questionnaire ask the same questions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Making at Least One Critical Error After Reading the Patient Information Leaflets (PIL) | 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. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP | 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. | Day 1 | 
| Percentage of Participants Making at Least One Critical Error After the Second Instruction From the HCP | 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. | Day 1 | 
| Percentage of Participants Making at Least One Overall Error After Reading the PIL | 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. | Day 1 | 
| Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP | 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. | Day 1 | 
| Percentage of Participants Making at Least One Overall Error After the Second Instruction From the HCP | 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. | Day 1 | 
| Number of Participants With Instructions (0, 1 or 2 Times) From the HCP Which Are Needed to Demonstrate Correct Inhaler Use | 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. | Day 1 | 
| The Median Time to Demonstrate Correct Inhaler Use (T1+T2) | 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. | Day 1 | 
| Time Taken to Read the PIL and Demonstrate Correct Inhaler Use (T1) | 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. | Day 1 | 
| 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) | 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. | Day 1 | 
| 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 | 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. | Day 1 | 
| Number of Participants With Treatment Preference Based on Responses to the Preference Questionnaire, Which Considered Overall Treatment Preference | 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. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HANDIHALER, ELLIPTA, TURBUHALER, DISKUS, COPD, critical error, inhaler preference