Clinical trial NCT03380429: A Clinical Study to Evaluate the Effect of the Connected Inhaler System (CIS) on Adherence to Maintenance Therapy in Poorly Controlled Asthmatic Subjects
Official title: An Open Label, Randomised, Parallel Group Clinical Study to Evaluate the Effect of the Connected Inhaler System (CIS) on Adherence to Relvar/Breo ELLIPTA Therapy, in Asthmatic Subjects With Poor Control
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Asthma
Keywords: Connected Inhaler System
Metered Dose Inhaler
ELLIPTA
RELVAR/BREO
Dry Powder Inhaler
Salbutamol
Asthma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2017-12-21
Enrollment: 437
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Eligible subjects will receive RELVAR/BREO maintenance therapy via ELLIPTA DPI and salbutamol rescue medication via MDI. Clip-on sensors will be attached to both inhalers which will provide data on maintenance therapy and rescue medication use to the subjects and their HCP. Subjects will be randomized into five treatment arms in a ratio of 1:1:1:1:1 depending on whether the data, from RELVAR/BREO ELLIPTA or RELVAR/BREO ELLIPTA and salbutamol MDI, is fed back to the subject or subject and HCP, or not at all.
Primary purpose: TREATMENT

Brief summary: GlaxoSmithKline (GSK) in collaboration with Propeller Health has developed a sensor, which can clip on to the ELLIPTA® dry powder inhaler (DPI) and monitor the time and date that the ELLIPTA DPI cover is fully opened and closed. Additionally, a sensor will be attached to the rescue medication metered dose inhaler (MDI). The data from both sensors will be fed back to the subject via an application (app) on smart phone and will be reviewed by the subject's health care professional (HCP) via an online dashboard. The sensors, app, dashboard and systems to provide data comprise the CIS. This study will be the first to evaluate the effect of CIS on adherence to maintenance therapy in subjects with uncontrolled asthma. This is an open-label, randomized, parallel group study in asthmatic subjects currently on a fixed dose inhaled corticosteroid (ICS)/long-acting beta 2 agonist (LABA) maintenance therapy. Eligible subjects will receive RELVAR®/BREO® maintenance therapy via ELLIPTA DPI and salbutamol rescue medication via MDI with sensors attached to both inhalers during the run-in period, which may last for up to 3 months. Eligible subjects will then be randomized into five treatment arms depending on whether the data, from RELVAR/BREO ELLIPTA or RELVAR/BREO ELLIPTA and salbutamol MDI, is fed back to the subject or subject and HCP, or not at all. The treatment period for the study is approximately 6 months and there will be a follow-up period one week post last visit. The total duration of a subject in the study will be approximately 9 months. RELVAR, BREO and ELLIPTA are registered trademarks of GlaxoSmithKline group of companies.


Eligibility criteria: Inclusion Criteria:

* Subjects aged 18 years or older, at the time of signing the informed consent.
* Subjects with documented physician diagnosis of asthma as their primary respiratory disease.
* ACT score \<20 at screening visit.
* Non-smokers (never smoked or not smoking for \>6 months with \<10 pack years history (Pack years = \[cigarettes per day smoked/20\] multiplied by number of years smoked).
* Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: (i) Not a woman of childbearing potential (WOCBP). (ii) A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 5 days\] after the last dose of study treatment.
* Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and protocol.
* Subject understands and is willing, able, and likely to comply with study procedures and restrictions.
* Subject must be able to read in a language supported by the smart phone app in their region.
* Subject must have been on maintenance therapy (Fixed dose combination ICS/LABA) for 3 months, cannot have changed dose in the month prior to screening and be able to change to an equivalent dose of RELVAR/BREO for the duration of the study. Other background asthma medication such as anti-leukotrienes and oral corticosteroids are permitted provided the dose has been stable for 1 month prior to screening.
* Subject must be able to change to Salbutamol/Albuterol MDI rescue for the duration of the study and judged capable of withholding albuterol/salbutamol for at least 6 hours prior to study visits.
* Subject must have their own Android or iPhone operating system (IOS) smart phone and a data package suitable for the installation and running of the app and sending and receiving data. Data used by the CIS is approximately 1 megabyte (MB) per month as a maximum; this is less data than a 1 minute video streamed from YouTube (2MB).
* Subjects must be willing and able to download the app on their personal smart phone and keep it turned on for the duration of the study. This will also require Bluetooth to be turned on for duration of the study. Subjects will also have to turn on mobile data for the app for the duration of study; unless travelling and when extra data roaming costs could be incurred.

Inclusion criteria for randomization:

* ACT score \<20 at randomization visit (visit 2).

Exclusion Criteria:

* Subjects with a known or suspected alcohol or drug abuse which in the opinion of the investigator could interfere with the subject's proper completion of the protocol requirement.
* History of life threatening asthma: Defined as an asthma episode that required intubation and/or was associated with hypercapnea, respiratory arrest or hypoxic seizures within the last 6 months.
* A lower respiratory tract infection within 7 days of the screening visit.
* 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 hypersensitivity/intolerance to any components of the study inhalers (example, 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.
* 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 analysis if the disease/condition exacerbated during the study.
* Subjects who have ever received treatment with biological based therapy example, omalizumab, mepolizumab, for asthma.
* Subjects who have received an investigational drug and/or medical device within 30 days of entry into this study (Screening), 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, employee of the participating investigator, or any family member of a Propeller Health employee.

Primary outcomes:
measure: Percentage of ELLIPTA Doses Taken (Daily Adherence) Between Month 4 and Month 6 as Determined by the Maintenance Sensor for Arms; ("Cohort 1: Data on Maintenance Use Supplied to Participant and HCP" and"Cohort 5: no Data Supplied to Participant or HCP")
timeFrame: Month 4 to Month 6
Secondary outcomes:
measure: Percentage of ELLIPTA Doses Taken (Daily Adherence) Between Month 4 and Month 6 as Determined by the Maintenance Sensor
timeFrame: Month 4 to Month 6
measure: Percentage of ELLIPTA Doses Taken (Daily Adherence) Between Month 1 and Month 3 as Determined by the Maintenance Sensor
timeFrame: Month 1 to Month 3
measure: Percentage of ELLIPTA Doses Taken (Daily Adherence) Between Month 1 and Month 6 as Determined by the Maintenance Sensor
timeFrame: Month 1 to Month 6
measure: Percentage of Rescue Free Days Between Month 4 and Month 6 as Determined by the Rescue Medication Sensor
timeFrame: Month 4 to Month 6
measure: Number of Doses of Rescue Medication Use Between Month 4 and Month 6 as Determined by the Rescue Medication Sensor
timeFrame: Month 4 to Month 6
measure: Change From Baseline in Asthma Control Test (ACT) Total Score
timeFrame: Baseline and Month 6
measure: Percentage of Participants Attaining Asthma Control (Percentage of Participants With an ACT Total Score >=20) at Month 6
timeFrame: Month 6
measure: Percentage of Participants With an Increase From Baseline >=3 in ACT Total Score at Month 6
timeFrame: Baseline and Month 6
measure: Percentage of Participants Who Have Either an ACT Total Score of >=20 and/or an Increase From Baseline >=3 in ACT Total Score at Month 6
timeFrame: Baseline and Month 6
Other outcomes:
Locations:
city: Aventura
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami
country: United States
facility: GSK Investigational Site
state: Florida
city: Flossmoor
country: United States
facility: GSK Investigational Site
state: Illinois
city: Glenview
country: United States
facility: GSK Investigational Site
state: Illinois
city: Hazelwood
country: United States
facility: GSK Investigational Site
state: Missouri
city: Charlotte
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Oklahoma City
country: United States
facility: GSK Investigational Site
state: Oklahoma
city: Medford
country: United States
facility: GSK Investigational Site
state: Oregon
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Greenfield
country: United States
facility: GSK Investigational Site
state: Wisconsin
city: Kelowna
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Ajax
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Burlington
country: Canada
facility: GSK Investigational Site
state: Ontario
city: London
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Sarnia
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Windsor
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Sherbrooke
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Victoriaville
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Quebec
country: Canada
facility: GSK Investigational Site
city: Ruedersdorf
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Darmstadt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Warendorf
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Salerno
country: Italy
facility: GSK Investigational Site
state: Campania
city: Pordenone
country: Italy
facility: GSK Investigational Site
state: Friuli-Venezia-Giulia
city: Palermo
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Breda
country: Netherlands
facility: GSK Investigational Site
city: Den Haag
country: Netherlands
facility: GSK Investigational Site
city: Groningen
country: Netherlands
facility: GSK Investigational Site
city: Hengelo
country: Netherlands
facility: GSK Investigational Site
city: Hoorn
country: Netherlands
facility: GSK Investigational Site
city: Zutphen
country: Netherlands
facility: GSK Investigational Site
city: Balenyà (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: La Coruña
country: Spain
facility: GSK Investigational Site
city: La Roca Del Valles (Barcelona)
country: Spain
facility: GSK Investigational Site
city: Loja/ Granada
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Peralada( Girona)
country: Spain
facility: GSK Investigational Site
city: Aylesbury
country: United Kingdom
facility: GSK Investigational Site
state: Buckinghamshire
city: Wigan
country: United Kingdom
facility: GSK Investigational Site
state: Lancashire
city: Wellingborough
country: United Kingdom
facility: GSK Investigational Site
state: Northamptonshire
city: Addlestone
country: United Kingdom
facility: GSK Investigational Site
state: Surrey
city: Rotherham
country: United Kingdom
facility: GSK Investigational Site
state: Yorkshire
city: Bristol
country: United Kingdom
facility: GSK Investigational Site
city: Chelmsford
country: United Kingdom
facility: GSK Investigational Site
city: Chertsey, Surrey
country: United Kingdom
facility: GSK Investigational Site
city: Harrogate
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Moore A, Preece A, Sharma R, Heaney LG, Costello RW, Wise RA, Ludwig-Sengpiel A, Mosnaim G, Rees J, Tomlinson R, Tal-Singer R, Stempel DA, Barnes N. A randomised controlled trial of the effect of a connected inhaler system on medication adherence in uncontrolled asthmatic patients. Eur Respir J. 2021 Jun 4;57(6):2003103. doi: 10.1183/13993003.03103-2020. Print 2021 Jun.