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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Device: ELLIPTA DPI; Device: AZ MDI; Device: GSK MDI

• Study Type: Interventional
• Enrollment (Actual): 324
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Huntington Beach, California, United States, 92648
      • GSK Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • GSK Investigational Site
    • Clearwater, Florida, United States, 33756
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • GSK Investigational Site
  • Massachusetts
    • North Dartmouth, Massachusetts, United States, 02747
      • GSK Investigational Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • GSK Investigational Site
  • Missouri
    • Columbia, Missouri, United States, 65203
      • GSK Investigational Site
    • Rolla, Missouri, United States, 65401
      • GSK Investigational Site
    • Warrensburg, Missouri, United States, 64093
      • GSK Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28277
      • GSK Investigational Site
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118-2040
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Texas
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • Waco, Texas, United States, 76712
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placebo ELLIPTA DPI (QD) in P1 and Placebo AZ MDI (BD) in P2; 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; 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); Device: AZ MDI; It is the placebo inhaler with clear liquid. It is given as oral inhalation (Inhalation Aerosol).
Experimental: Placebo AZ MDI (BD) in P1 and Placebo ELLIPTA DPI (QD) in P2; 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; 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); Device: AZ MDI; It is the placebo inhaler with clear liquid. It is given as oral inhalation (Inhalation Aerosol).
Experimental: Placebo ELLIPTA DPI (QD) in P1 and Placebo GSK MDI (BD) in P2; 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; 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); Device: GSK MDI; It is the placebo inhaler with clear liquid containing propellant (1,1,1, 2- Tetrafluoroethane). It is given as oral inhalation (Inhalation Aerosol).
Experimental: Placebo GSK MDI (BD) in P1 and Placebo ELLIPTA DPI (QD) in P2; 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; 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); Device: GSK MDI; It is the placebo inhaler with clear liquid containing propellant (1,1,1, 2- Tetrafluoroethane). It is given as oral inhalation (Inhalation Aerosol).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Kerwin EM, Preece A, Brintziki D, Collison KA, Sharma R. ELLIPTA Dry Powder Versus Metered-Dose Inhalers in an Optimized Clinical Trial Setting. J Allergy Clin Immunol Pract. 2019 Jul-Aug;7(6):1843-1849. doi: 10.1016/j.jaip.2019.02.023. Epub 2019 Mar 2.

Study record dates

Study Major Dates

• Study Start (Actual): August 22, 2016
• Primary Completion (Actual): December 15, 2016
• Study Completion (Actual): December 15, 2016

Study Registration Dates

• First Submitted: June 6, 2016
• First Submitted That Met QC Criteria: June 6, 2016
• First Posted (Estimate): June 9, 2016

Study Record Updates

• Last Update Posted (Actual): July 2, 2019
• Last Update Submitted That Met QC Criteria: June 24, 2019
• Last Verified: June 1, 2019

More Information

Terms related to this study

• Keywords: Dry powder inhaler; ELLIPTA; metered dose inhaler
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: 204980

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR)