Phase IV Study in Asthma Subjects for Dry Powder Inhaler (DPI) Versus (vs) Metered Dose Inhaler (MDI) Correct Use

Study Overview
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Brief Summary
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The study is conducted to evaluate the potentially improved patient handling of the ELLIPTA Dry Powder Inhaler (DPI). Therefore, the study aims to evaluate errors encountered by subject with asthma during handling ELLIPTA DPI relative to two metered dose inhalers (MDI), a GSK MDI and the AstraZeneca (AZ) MDI. It is a randomised, multi-centre, open-label, cross-over study comparing placebo ELLIPTA DPI with placebo MDI (GSK and AZ) to assess correct inhaler use. No active drug will be used in this study in order to prevent any drug-related effects. Approximately, 152 subjects will be randomized to receive ELLIPTA DPI inhaler and 152 will be randomized to receive one of the MDI inhalers, for use during the first period (P) (approximately 28 days). At Visit 2 (Day 28) all subjects previous receiving the ELLIPTA DPI will be randomized to receive one of the MDI inhalers and all subjects who received a MDI in the previous period will receive the ELLIPTA DPI for use during second period (approximately 28 days). Subjects will continue taking their asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period. ELLIPTA is a registered trademark of the GSK group of companies.

Official Title
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204980: An Open-label Study to Evaluate the Correct Use of Placebo ELLIPTA™ Dry Powder Inhaler (DPI) Compared to Placebo Metered Dose Inhalers (MDI) in Subjects With Moderate Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Device: ELLIPTA DPI
* Device: GSK MDI
* Device: AZ MDI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects aged 18 years or older, at the time of signing the informed consent Documented history of moderate persistent asthma Asthma Control Test (ACT) score >=20 Male or Females (who are not pregnant or planning pregnancy during the study or not lactating) Capable of giving signed informed consent which includes compliance with the requirements and restrictions 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 English Should not have received maintenance therapy via MDI or ELLIPTA in the past six months (DISKUS (trade name owned by GSK group of companies under license), TWISTHALER (trade name owned by Merck Sharp & Dohme Corporation, a subsidiary of Merck & Co, under license, etc are acceptable). Subject must be on maintenance therapy for 3 months, have not changed dose in the month prior to inclusion and be able to continue using their maintenance therapy throughout the study Requires Short-acting-beta-agonist (SABA) for symptom control =<2 days/week. Use of SABA prior to exercise for the prevention of exercise induced bronchoconstriction is exclusionary. Exclusion Criteria: 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 Current smokers or subjects with a smoking history of 10 pack-years or more (example, 20 cigarettes/day for 10 years) are not eligible. A subject may not have used tobacco products within the past year (i.e., cigarettes, cigars, or pipe tobacco) Concurrent diagnosis of chronic obstructive pulmonary disease (COPD) or other respiratory disorders including active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases History of life threatening asthma or has experienced more than 1 exacerbation which required oral/systemic corticosteroids in the 12 months prior to Visit 1 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 Historical or current evidence of clinically significant or rapidly progressing or unstable cardiovascular, neurological, cardiovascular, neurological, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the affect the analysis if the disease/condition exacerbated during the study 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 A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

Ages Eligible for Study
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Minimum Age: 18 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: Placebo ELLIPTA DPI (QD) in P1 and Placebo AZ MDI (BD) in P2<br>Eligible subject will receive ELLIPTA DPI taken as one inhalation once daily (QD) for 28 days and Placebo AZ MDI taken as two inhalations twice daily (BD) for next 28 days. Subject will continue to take asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period | Device: ELLIPTA DPI<br>* It is the inhaler with two blister strips containing white coloured powder, one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. It is given as oral inhalation (Inhalation powder)<br>Device: AZ MDI<br>* It is the placebo inhaler with clear liquid. It is given as oral inhalation (Inhalation Aerosol).<br>|
| Experimental: Placebo AZ MDI (BD) in P1 and Placebo ELLIPTA DPI (QD) in P2<br>Eligible subject will receive AZ MDI taken as two inhalations twice daily for 28 days and Placebo ELLIPTA DPI taken as one inhalation once daily for next 28 days. Subject will continue to take asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period | Device: ELLIPTA DPI<br>* It is the inhaler with two blister strips containing white coloured powder, one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. It is given as oral inhalation (Inhalation powder)<br>Device: AZ MDI<br>* It is the placebo inhaler with clear liquid. It is given as oral inhalation (Inhalation Aerosol).<br>|
| Experimental: Placebo ELLIPTA DPI (QD) in P1 and Placebo GSK MDI (BD) in P2<br>Eligible subject will receive ELLIPTA DPI taken as one inhalation once daily for 28 days and Placebo GSK MDI taken as two inhalations twice daily for next 28 days. Subject will continue to take asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period. | Device: ELLIPTA DPI<br>* It is the inhaler with two blister strips containing white coloured powder, one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. It is given as oral inhalation (Inhalation powder)<br>Device: GSK MDI<br>* It is the placebo inhaler with clear liquid containing propellant (1,1,1, 2- Tetrafluoroethane). It is given as oral inhalation (Inhalation Aerosol).<br>|
| Experimental: Placebo GSK MDI (BD) in P1 and Placebo ELLIPTA DPI (QD) in P2<br>Eligible subject will receive GSK MDI taken as two inhalations twice daily for 28 days and Placebo ELLIPTA DPI taken as one inhalation once daily for next 28 days. Subject will continue to take asthma maintenance treatment and limited rescue albuterol MDI during the entire 56-day study period | Device: ELLIPTA DPI<br>* It is the inhaler with two blister strips containing white coloured powder, one placebo strip containing lactose monohydrate and a second placebo strip containing lactose monohydrate blended with magnesium stearate. It is given as oral inhalation (Inhalation powder)<br>Device: GSK MDI<br>* It is the placebo inhaler with clear liquid containing propellant (1,1,1, 2- Tetrafluoroethane). It is given as oral inhalation (Inhalation Aerosol).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Zero Errors in ELLIPTA DPI Versus GSK MDI and AZ MDI After 28 Days of Use in Each Treatment Phase | A checklist for correct use of each inhaler was developed based on the steps identified in the package insert. Baseline assessment was conducted when the par were dispensed the inhaler and were guided by a trained healthcare provider (HCP) to demonstrate correct use of the assigned inhaler. A second assessment was conducted after each 28 day dosing period without instruction by HCP. The Correct Use Check list was completed by HCP at each visit. Percentage of par with zero errors in inhaler use at Day 28, was analyzed using a Mainland-Gart test for each ELLIPTA versus MDI comparison separately (Sub-study 1: ELLIPTA vs GSK MDI and Sub-study 2: ELLIPTA vs AZ MDI). For each ELLIPTA vs MDI analyses, only par who made no error in any of the inhalers and at least one error on the other inhaler (discordant cases) were included in the analysis. NA indicates that par did not receive the inhaler in that particular sub-study. | Up to Day 56 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Errors by Type for ELLIPTA After 28 Days of Use in Each Treatment Phase | The occurrence of each type of error while using ELLIPTA inhaler was evaluated based on the information collected in the Correct Use Checklists. The number of errors for each type of inhaler was assessed at Visit 2 and Visit 3. The par were counted more than once depending on the reasons for incorrect use. Only par who made at least one error was included in the summary (represented by the number of Participants). | Up to Day 56 | 
| Frequency of Errors by Type for MDI After 28 Days of Use in Each Treatment Phase | The occurrence of each type of error while using GSK MDI in Sub-Study 1 and AZ MDI in Sub-Study 2 was evaluated based on the information collected in the Correct Use Checklists. The number of errors for each type of inhaler was assessed at Visit 2 and Visit 3. The par were counted more than once depending on the reasons for incorrect use. The number of errors is reported as NA for the type of error which was not applicable to the particular inhaler type. Only par who made at least one error are included in the summary (represented by the number of Participants). | Up to Day 56 | 
| Number of Errors Per Participant for Each Inhaler After 28 Days of Use (All Evaluable Par) | The number of errors per par for each inhaler (ELLIPTA and GSK MDI or AZ MDI) was evaluated based on the information collected in the Correct Use Checklists. The number of errors per par was summarised as continuous data by inhaler for each of the ELLIPTA versus MDI comparisons. NA indicates that the par did not receive the inhaler in that particular sub-study. | Up to Day 56 | 
| Number of Errors Per Participant for Each After 28 Days of Use (Par With at Least One Error) | The number of errors for each inhaler (ELLIPTA and GSK MDI or AZ MDI) in par with one or more errors were evaluated based on the information collected in the Correct Use Checklists. The number of errors per par was summarised as continuous data by inhaler for each of the ELLIPTA versus MDI comparisons. NA indicates that the par. did not receive the inhaler in that particular sub-study. Only those par who made at least one error were included in the summary (represented by n=X, X in the category titles). | Up to Day 56 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ELLIPTA, metered dose inhaler, Dry powder inhaler