Study of Inhaler Device Attributes Investigating Critical and Overall Errors, Ease of Use, and Preference Between a Number of Inhaler Devices

Study Overview
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Brief Summary
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This is a randomised, open-label, placebo, crossover, multicentre study with a single visit. The study will comprise five sub-studies. Subjects will receive inactive treatment (placebo) via the ELLIPTA® inhaler and one of the other inhaler devices depending on the sub-study they are randomised to. Only subjects who are naïve to the ELLIPTA inhaler and to one of the other inhaler devices that will be used in this study will be included. Furthermore, subjects who are naïve to the BREEZEHALER® and HANDIHALER® inhalers must be naïve to all other inhaler devices that requires a capsule. The study will be conducted in the UK and the Netherlands, and comprises one visit only. A sufficient number of subjects (at least 600) with COPD will be screened and 570 will be randomised to one of five sub-studies. Eligible subjects will be allocated to one of the sub-studies depending on their experience of using the other inhaler (i.e., depending on which other inhaler they are naïve to). This study is designed to assess the proportion of COPD subjects making critical and overall (i.e., critical and non-critical errors) errors in using ELLIPTA inhaler and other commercially available inhaler devices such as the TURBUHALER®, HANDIHALER, BREEZHALER, MDI and DISKUS®/ACCUHALER® inhalers. This study will also assess the 'ease of use' and preference between the ELLIPTA inhaler and the other commercially available inhaler devices. ELLIPTA, DISKUS, and ACCUHALER are registered trademarks of the GSK group of companies. TURBUHALER is a registered trademark of AstraZeneca. HANDIHALER is a registered trademark of Boehringer Ingelheim Pharma GmbH & Co. KG. BREEZHALER is a registered trademark of Novartis AG.

Official Title
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An Open-label Study of Inhaler Device Attributes Investigating Critical and Overall Errors, Ease of Use, and Preference Between a Number of Inhaler Devices (ELLIPTA, TURBUHALER, HANDIHALER, BREEZHALER, MDI, and DISKUS/ACCUHALER) in Adult Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Pulmonary Disease, Chronic Obstructive

Intervention / Treatment
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* Device: ELLIPTA
* Device: DISKUS/ACCUHALER
* Device: MDI
* Device: TURBUHALER
* Device: HANDIHALER
* Device: BREEZEHALER


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent: Subject must give their signed and dated written informed consent to participate in the study; Subject understands and is willing, able, and likely to comply with study procedures and restrictions; Subject must be able to read, comprehend, and record information in Dutch and/or English. Age: >=40 years of age Gender: Male or female subjects. Primary diagnosis of COPD: subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society. Comorbidities (rheumatoid arthritis or other locomotor problems, visual impairment, and depression or anxiety) will be documented as relevant to inhaler use. COPD treatment: All patients should be currently receiving treatment for COPD. Must be naïve to using ELLIPTA inhaler and at least one other inhaler device. Subjects who are naïve to the BREEZEHALER and HANDIHALER inhalers must be naïve to all other inhaler devices that requires a capsule. Exclusion Criteria: Asthma: Subjects with a current diagnosis of asthma only. Note: Subjects with a prior history of asthma are eligible if they have a current diagnosis of COPD. Contraindications: A history of allergy or hypersensitivity to lactose/milk protein or magnesium stearate or to any other excipient. Subjects who are currently participating in another randomised pharmacological interventional trial. Inability to Read: 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sub-Study 1<br>Subjects will be randomized to either use ELLIPTA inhaler first and then DISKUS/ACCUHALER inhaler or use DISKUS/ACCUHALER inhaler first and then ELLIPTA inhaler. | Device: ELLIPTA<br>* Dry powder inhaler (placebo) with two blister strips. One placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.<br>Device: DISKUS/ACCUHALER<br>* Placebo inhaler with one blister strip containing lactose monohydrate.<br>|
| Experimental: Sub-Study 2<br>Subjects will be randomized to either use ELLIPTA inhaler first and then MDI inhaler or use MDI inhaler first and then ELLIPTA inhaler. | Device: ELLIPTA<br>* Dry powder inhaler (placebo) with two blister strips. One placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.<br>Device: MDI<br>* Placebo inhaler containing propellant (1,1,1, 2-Tetrafluoroethane).<br>|
| Experimental: Sub-Study 3<br>Subjects will be randomized to either use ELLIPTA inhaler first and then TURBUHALER inhaler or use TURBUHALER inhaler first and then ELLIPTA. | Device: ELLIPTA<br>* Dry powder inhaler (placebo) with two blister strips. One placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.<br>Device: TURBUHALER<br>* Placebo inhaler containing lactose monohydrate.<br>|
| Experimental: Sub-Study 4<br>Subjects will be randomized to either use ELLIPTA inhaler first and then HANDIHALER inhaler or use HANDIHALER inhaler first and then ELLIPTA inhaler. | Device: ELLIPTA<br>* Dry powder inhaler (placebo) with two blister strips. One placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.<br>Device: HANDIHALER<br>* Placebo inhaler containing lactose monohydrate in a capsule.<br>|
| Experimental: Sub-Study 5<br>Subjects will be randomized to either use ELLIPTA inhaler first and then BREEZEHALER inhaler or use BREEZEHALER inhaler first and then ELLIPTA inhaler. | Device: ELLIPTA<br>* Dry powder inhaler (placebo) with two blister strips. One placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate.<br>Device: BREEZEHALER<br>* Placebo inhaler containing lactose monohydrate in a capsule.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Made at Least One Critical Error After Reading the Patient Information Leaflet | A critical error was defined as an error that was most likely to result in no or only minimal medication being inhaled. The errors considered as critical errors while handling the inhaler devices were failed to open cover, lever was not pushed back, shook the device after dose preparation, exhaled directly into mouthpiece, no seal by the lips round the mouthpiece during the inhalation. As per the crossover study design participants received placebo via the ELLIPTA inhaler first and then non-ELLIPTA inhaler or non-ELLIPTA inhaler first and then ELLIPTA on Day 1. The percentage of participants who made at least one critical error was reported for each inhaler regardless sequence. | Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Made at Least One Overall Error After Reading the Patient Information Leaflet | An overall error includes a critical and non-critical error. Any error made by the participants while demonstrating the use of the inhaler after reading the patient instruction leaflet was recorded by health care professional (HCP). The percentage of participants who made at least one overall error was reported. As per the crossover study design participants received placebo via the ELLIPTA inhaler first and then non-ELLIPTA inhaler or non-ELLIPTA inhaler first and then ELLIPTA on Day 1. | Day 1 | 
| Percentage of Participants Making at Least One Critical Error After the First Instruction From the HCP | A critical error was defined as an error that was most likely to result in no or only minimal medication being inhaled. The errors considered as critical errors while handling the inhaler devices were failed to open cover, lever was not pushed back, shook the device after dose preparation, exhaled directly into mouthpiece, no seal by the lips round the mouthpiece during the inhalation. As per the crossover study design participants received placebo via the ELLIPTA inhaler first and then non-ELLIPTA inhaler or non-ELLIPTA inhaler first and then ELLIPTA on Day 1. If the participant made any error while demonstrating the use of the inhaler after reading the patient instruction leaflet, the HCP demonstrated the correct usage of the inhaler to the participant. The participants were then asked to demonstrate inhaler use again. If any further critical error were made by the participant, the error were recorded by HCP. | Day 1 | 
| Percentage of Participants Making at Least One Overall Error After the First Instruction From the HCP | An overall error includes a critical and non-critical error. If the participant made any error while demonstrating the use of the inhaler after reading the patient instruction leaflet, the HCP demonstrated the correct usage of the inhaler to the participant. The participants were then asked to demonstrate inhaler use again. If any further error was made by the participant was recorded by HCP. | Day 1 | 
| Number of Participants Needed Instructions From HCP (Maximum Three Times) to Demonstrate Adequate Inhalation Technique | If the participant made any error while demonstrating the use of the first inhaler after reading the patient instruction leaflet, the HCP demonstrated the correct usage of the inhaler to the participant. The participant was then asked to demonstrate inhaler use again. Any errors made by the participant were recorded by the HCP. The same procedure was repeated if the participant continues to make errors in the use of the inhaler. In total, the HCP demonstrated the use of the inhaler up to three times. Same procedure was followed for second inhaler. The number of participants who demonstrated the adequate inhalation technique after third time instructions from HCP was reported. | Day 1 | 
| Percentage of Participants Who Overall Preferred the ELLIPTA Device Compared to Non-ELLIPTA Inhalers as Assessed by the Preference Questionnaire | After completing the demonstration procedures of the inhalers, the HCP asked the participant a number of questions from preference questionnaire. Preference questionnaire consisted of eight questions related to both inhalers used during the study. Each question had one response to choose from 3 preference options (Other inhaler device, ELLIPTA inhaler device and No preference). The number of participants who overall preferred the ELLIPTA device compared to non-ELLIPTA inhalers (First question in the preference questionnaire) were reported. | Day 1 | 
| Percentage of Participants Who Overall Found the ELLIPTA Device Easy to Use Compared With Non-ELLIPTA Inhalers as Assessed by the Ease of Use Questionnaire | After completing the demonstration procedures of the inhalers, the HCP asked the participant a number of questions from ease of use questionnaire. Ease of use questionnaire consisted of six questions each for ELLIPTA inhaler and the other inhaler under study. Each question had one response to choose from 5 options of ease of use (Very easy, easy, neutral, difficult and very difficult). Based upon the response given by the participants the number of participants who rated ease of use higher for ELLIPTA, higher for non- ELLIPTA, or rated the same were reported | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BREEZHALER, DISKUS/ACCUHALER, MDI, Inhaler preference, Overall inhaler error, HANDIHALER, Ease of use, TURBUHALER, ELLIPTA, Critical inhaler error