Effectiveness of Fluticasone Furoate/ Umeclidinium/ Vilanterol (FF/UMEC/VI) Using the Connected Inhaler System (CIS) as Compared With Fluticasone Proprionate/ Salmeterol (FP/SAL) Plus Tiotropium (TIO) in Inadequately Controlled Asthma
- Conditions
- Asthma
- Interventions
- Drug: FP/SALDrug: Albuterol/salbutamolDevice: ELLIPTA DPIDevice: Metered Dose InhalerDevice: DISKUS DPIDevice: Connected Inhaler SystemDevice: RESPIMAT inhaler
- Registration Number
- NCT03376932
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
Asthma is a common, chronic respiratory disease affecting 1-18 percent of the population. It is accepted that much of the uncontrolled asthma is due to poor adherence and asthma outcomes in such cases may improve simply by increasing adherence to available treatments. GlaxoSmithKline (GSK) has developed a sensor, which clips on to the ELLIPTA® dry powder inhaler (DPI). This will inform subjects if/when they have taken their medication that is in the ELLIPTA inhaler, as well as other information, including: asthma management strategies, tracking of symptoms, asthma triggers, medication reminders and daily asthma forecasts. The sensors, application (app), and provider portal that provide data are subsequently described as the CIS. The combination of once-daily FF/UMEC/VI with the CIS will improve the disease management and adherence. Thus, this study is designed to study the effectiveness and adherence of single inhaler triple therapy (SITT) of FF/UMEC/VI with the CIS as compared to multiple inhaler triple therapy (MITT) of the combination of FP/SAL plus TIO without CIS in subjects with inadequately controlled asthma. The study randomization will be stratified by pre-study inhaled corticosteroids (ICS) dosage strength (mid- or high-dose). Subjects will be randomized in a 1:1 ratio to receive either FF/UMEC/VI delivered via the ELLIPTA DPI with the CIS or FP/SAL delivered via the DISKUS® DPI (with sensor only) plus TIO delivered via the RESPIMAT inhaler (without sensor). The maximum study duration will be approximately 29 weeks, which comprised of prescreen/ screening/ randomization period of up to 4 weeks, 24-week treatment period and a 1-week follow-up period. Approximately 1006 subjects will be randomized in the study. ELLIPTA and DISKUS are registered trademarks of GlaxoSmithKline (GSK) group of companies.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- WITHDRAWN
- Sex
- All
- Target Recruitment
- Not specified
- Subjects must have their own Android or iPhone operating system (IOS) mobile device (example given [e.g.] smart phone or tablet) 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 mobile device 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.
- Subjects must be 18 years of age or older at the time of signing the informed consent.
- Subjects with a documented diagnosis of asthma by a respiratory physician or subjects with a documented asthma diagnosis by their general practitioner (GP) are required to have spirometry consistent with the diagnosis of asthma (e.g., reduced FEV1, reduced FEV1/forced vital capacity (FVC), or variable airflow obstruction) at or before Visit 0.
- Subjects who are able to perform spirometry that conforms to American Thoracic Society/ European Respiratory Society(ATS/ERS) technical standards at Visit 0 or Visit 1.
- Subjects are eligible if they require daily ICS/ long-acting beta-agonist (LABA) therapy (with a stable total daily dose of ICS of >250 microgram per day [mcg/day] FP, or equivalent) for at least 4 weeks prior to screening. Dosing regimen (once or twice daily to equal the total daily dose) should be restricted to the current local product labels/treatment guidelines.
- Subjects with inadequately controlled asthma (ACT total score <20) despite ICS/LABA maintenance therapy at Visit 1.
- Male or Female subjects will be included in the study. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: not a woman of childbearing potential (WOCBP) or 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. The Investigator is responsible for ensuring that subject understands how to properly use these methods of contraception.
- Capable of giving signed informed consent.
- Subjects with current evidence of pneumonia, active tuberculosis, lung cancer, significant bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases including chronic obstructive pulmonary disease (COPD) or abnormalities other than asthma.
- Subjects with historical or current evidence of uncontrolled or clinically significant disease. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the subject at risk through participation (e.g. very low body mass index [BMI] or severely malnourished), or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Subjects with any of the following at screening would be excluded: myocardial infarction or unstable angina in the last 6 months; unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.
- Moderate or severe hepatic impairment in subjects receiving high dose ICS.
- Subjects with a history of allergy or hypersensitivity to any corticosteroid, anticholinergic/ muscarinic receptor antagonist, beta2-agonist, lactose/milk protein or magnesium stearate are excluded from participation in this study.
- Subjects with a medical condition such as narrow-angle glaucoma, urinary retention, prostatic hypertrophy or bladder neck obstruction should only be included if in the opinion of the Investigator the benefit outweighs the risk and that the condition would not contraindicate study participation.
- Subjects with active uncontrolled psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.
- 30 days or within 5 drug half-lives of the investigational drug (whichever is longer).
- Subjects who are medically unable to withhold their albuterol/salbutamol for the 6-hour period required prior to spirometry testing at each study visit.
- Smokers will be excluded as follows: current smokers (defined as subjects who have used inhaled tobacco products within the 12 months prior to screening [that is {i.e.}, cigarettes, e-cigarettes/vaping, cigars or pipe tobacco]); former smokers with a smoking history of >=10 pack years (e.g., >=20 cigarettes/day for 10 years).
- Subjects unable to comply with the study procedures due to infirmity, disability, or geographic location.
- Study Investigators, sub-Investigators, study coordinators, employees of a participating Investigator or study site, or immediate family members of the aforementioned that is involved with this study.
- In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete study related materials.
- Subjects who have taken part in more than 1 clinical trial in the 12 months prior to Visit 1 and/or subjects who have taken part in any of the following clinical trials in the 12 months prior to Visit 1: a clinical trial including audio and/or visual reminders for the subject to take their study treatment; any clinical trial during the 4 weeks prior to Visit 1;GSK study 207040.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg Albuterol/salbutamol Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS Metered Dose Inhaler Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FF/UMEC/VI (100/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol metered dose inhalers (MDIs) as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS Albuterol/salbutamol Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FF/UMEC/VI (100/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol metered dose inhalers (MDIs) as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS Albuterol/salbutamol Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FF/UMEC/VI (200/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg Albuterol/salbutamol Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS Connected Inhaler System Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FF/UMEC/VI (100/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol metered dose inhalers (MDIs) as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS ELLIPTA DPI Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FF/UMEC/VI (100/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol metered dose inhalers (MDIs) as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS ELLIPTA DPI Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FF/UMEC/VI (200/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg RESPIMAT inhaler Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg FP/SAL Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS Connected Inhaler System Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FF/UMEC/VI (200/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg Tiotropium Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg DISKUS DPI Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS Metered Dose Inhaler Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FF/UMEC/VI (200/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg FP/SAL Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg Metered Dose Inhaler Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg Metered Dose Inhaler Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg DISKUS DPI Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg RESPIMAT inhaler Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FP/SAL (500/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily given in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS FF/UMEC/VI Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving high-dose of ICS during pre-study will be administered with FF/UMEC/VI (200/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study. Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS FF/UMEC/VI Eligible subjects will receive SITT of FF/UMEC/VI based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FF/UMEC/VI (100/62.5/25) mcg inhalation powder via ELLIPTA DPI, once daily in the morning or evening with the CIS. Subjects will also receive albuterol/salbutamol metered dose inhalers (MDIs) as a rescue medication throughout the study. Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg Tiotropium Eligible subjects will receive MITT of FP/SAL+ TIO based on their pre-study ICS dosage strength (mid- or high-dose). Subjects receiving mid-dose of ICS during pre-study will be administered with FP/SAL (250/50) mcg inhalation powder via DISKUS DPI with sensor, twice daily in the morning or evening plus TIO 5 mcg via RESPIMAT inhaler without sensor, once daily in the morning or evening. Subjects will also receive albuterol/salbutamol MDI as a rescue medication throughout the study.
- Primary Outcome Measures
Name Time Method Percentage of subjects who have an asthma control test (ACT) total score of >=20 Up to 24 weeks The ACT is a self-administered tool to identify subjects with poorly controlled asthma. It is a 5-item questionnaire measuring the frequency of shortness of breath, general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall assessment of asthma control. The response options for all these questions consist of a 5-point scale, ranging from 1 (all the time or not controlled at all for symptoms/activities) to 5 (not at all or completely controlled).
Percentage of subjects with an increase from Baseline of >=3 in ACT total score Baseline and up to 24 weeks The ACT is a self-administered tool to identify subjects with poorly controlled asthma. It is a 5-item questionnaire measuring the frequency of shortness of breath, general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall assessment of asthma control. The response options for all these questions consist of a 5-point scale, ranging from 1 (all the time or not controlled at all for symptoms/activities) to 5 (not at all or completely controlled).
- Secondary Outcome Measures
Name Time Method Number of subjects with AEs leading to dose modification Up to 25 weeks An AE is any untoward medical occurrence in a subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of subjects with AEs leading to dose modification will be evaluated.
Percentage of subjects who have a decrease from Baseline of >=4 in St George's Respiratory Questionnaire (SGRQ) total score Baseline and up to 24 weeks The SGRQ is designed to measure quality of life in subjects with diseases of airway obstruction, measuring symptoms, impact, and activity. It is a well-established instrument, comprising 50 questions to be self-completed by the subject. Higher scores indicate worse health status, and a change of 4 points is considered a clinically relevant change.
Percentage of ELLIPTA versus DISKUS doses taken as prescribed over the 24-week treatment period Up to 24 weeks The number of ELLIPTA and DISKUS doses taken will be collected using clip on sensors attached to the inhalers. The sensors will record the precise time and date when the mouthpiece cover of the inhalers has been opened and closed. Adherence is defined as the percentage of ELLIPTA and DISKUS doses taken as prescribed over the study treatment period as determined by the maintenance sensor records of date and time (within a 24-hour time period/window).
Change from Baseline in trough forced expiratory volume in 1 second (FEV1) Baseline and up to 24 weeks FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the mean FEV1 value obtained prior to the last dose of investigational product.
Number of subjects with serious adverse events (SAEs) including hospitalizations for asthma Up to 29 weeks from screening Any untoward event resulting in death, life threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment will be categorized as an SAE. Number of subjects with incidences and type of SAEs including hospitalizations for asthma will be evaluated.
Number of subjects with AEs leading to withdrawal or discontinuation of treatment Up to 25 weeks An AE is any untoward medical occurrence in a subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. Number of subjects with AEs leading to withdrawal or discontinuation of treatment will be evaluated.
Annualized rate of moderate and/or severe asthma exacerbations Up to 24 weeks Annualized rate of moderate/severe asthma exacerbations will be compared to evaluate the effectiveness of FF/UMEC/VI with CIS on improving asthma control compared with FP/SAL+TIO after 24 weeks of treatment. Moderate asthma exacerbation is defined as deterioration in asthma symptoms, deterioration in lung function, or increased rescue bronchodilator use lasting for at least 2 days or more. Severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids, or an increase from a stable maintenance dose, for at least 3 days or an inpatient hospitalization or emergency department visit due to asthma that required systemic corticosteroids.