A Randomised Open-label Study to Compare the Effectiveness of the Fixed Dose Combination of FF/UMEC/VI (Using the Connected Inhaler System) With the Combination of FP/SAL Plus Tiotropium (Without the Connected Inhaler System) in Participants With Inadequately Controlled Asthma
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 主要终点
- Percentage of subjects who have an asthma control test (ACT) total score of >=20
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
盲法说明
This will be an open-label study. Hence, masking will not be provided.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •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
- •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
- •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.
排除标准
- •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.
研究组 & 干预措施
Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS
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.
干预措施: FF/UMEC/VI (Drug)
Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS
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.
干预措施: Albuterol/salbutamol (Drug)
Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS
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.
干预措施: ELLIPTA DPI (Device)
Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS
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.
干预措施: Metered Dose Inhaler (Device)
Subjects receiving FF/UMEC/VI (100/62.5/25) mcg+ CIS
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.
干预措施: Connected Inhaler System (Device)
Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS
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.
干预措施: FF/UMEC/VI (Drug)
Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS
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.
干预措施: Albuterol/salbutamol (Drug)
Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS
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.
干预措施: ELLIPTA DPI (Device)
Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS
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.
干预措施: Metered Dose Inhaler (Device)
Subjects receiving FF/UMEC/VI (200/62.5/25) mcg+ CIS
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.
干预措施: Connected Inhaler System (Device)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: FP/SAL (Drug)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: Tiotropium (Drug)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: Albuterol/salbutamol (Drug)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: DISKUS DPI (Device)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: RESPIMAT inhaler (Device)
Subjects receiving FP/SAL(250/50) mcg + TIO 5 mcg
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.
干预措施: Metered Dose Inhaler (Device)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: FP/SAL (Drug)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: Tiotropium (Drug)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: Albuterol/salbutamol (Drug)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: DISKUS DPI (Device)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: RESPIMAT inhaler (Device)
Subjects receiving FP/SAL(500/50) mcg + TIO 5 mcg
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.
干预措施: Metered Dose Inhaler (Device)
结局指标
主要结局
Percentage of subjects who have an asthma control test (ACT) total score of >=20
时间窗: 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
时间窗: 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).
次要结局
- Number of subjects with AEs leading to dose modification(Up to 25 weeks)
- 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)
- Percentage of ELLIPTA versus DISKUS doses taken as prescribed over the 24-week treatment period(Up to 24 weeks)
- Change from Baseline in trough forced expiratory volume in 1 second (FEV1)(Baseline and up to 24 weeks)
- Number of subjects with serious adverse events (SAEs) including hospitalizations for asthma(Up to 29 weeks from screening)
- Number of subjects with AEs leading to withdrawal or discontinuation of treatment(Up to 25 weeks)
- Annualized rate of moderate and/or severe asthma exacerbations(Up to 24 weeks)