An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol 100/25 Microgram (mcg) Inhalation Powder, Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Fluticasone Propionate 250 mcg Inhalation Powder in Adults and Adolescents With Persistent Asthma

Phase 3

Completed

• Conditions: Asthma
• Interventions: Drug: Fluticasone Furoate/Vilanterol 100/25 mcg via ELLIPTA inhaler; Drug: Placebo inhalation powders via ELLIPTA inhaler; Drug: Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler; Drug: Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler; Drug: Placebo inhalation powder via ACCUHALER/DISKUS inhaler

• Registration Number: NCT02301975
• Lead Sponsor: GlaxoSmithKline

Brief Summary

This study is a randomized, double-blind, double-dummy, parallel group, multicenter, non-inferiority study. The study will enroll adult and adolescent asthmatic subjects who are currently receiving mid dose inhaled corticosteroids (ICS) plus long-acting beta2-agonist (LABA) (equivalent to fluticasone propionate \[FP\]/salmeterol 250/50 microgram \[mcg\]twice daily \[BD\]), either via a fixed dose combination product or through separate inhalers. The study consists of a LABA washout period of 5 days and a run-in period of 4 weeks, followed by a treatment period of 24 weeks, and a follow up contact period of one week. The total duration of the study is 30 weeks. Approximately 1461 subjects will be randomized to one of the following three treatments (487 per treatment): fluticasone furoate (FF)/vilanterol (VI) 100/25 mcg once daily (OD) in the evening (PM) via ELLIPTA™ inhaler plus placebo BD via ACCUHALER™/DISKUS™; FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler; FP 250 mcg BD via ACCUHALER/DISKUS inhaler plus placebo OD (PM) via ELLIPTA inhaler. In addition, all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as needed to treat acute asthma symptoms. This study will determine if FF/VI 100/25 mcg OD via ELLIPTA inhaler is non-inferior to FP/salmeterol 250/50 mcg BD via ACCUHALER/DISKUS inhaler in adult and adolescent asthmatic subjects already adequately controlled on a twice-daily ICS/LABA.

SERETIDE, ELLIPTA, ACCUHALER, RELVAR, and DISKUS are trademarks of the GlaxoSmithKline Group of Companies.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-11-24
• Study First Submitted QC: 2014-11-24
• Study First Posted: 2014-11-26
• Study Start: 2015-03-01
• Primary Completion: 2016-11-01
• Study Completion: 2016-11-25
• Results First Submitted: 2017-05-08
• Results First Submitted QC: 2017-05-08
• Results First Posted: 2017-06-12
• Status Verified: 2018-08
• Last Update Submitted: 2018-08-02
• Last Update Posted: 2018-08-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1526

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluticasone Propionate/Salmeterol 250/50 mcg	Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler	FP/Salmeterol 250/50 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.
Fluticasone Propionate 250 mcg	Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler	FP 250 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.
Fluticasone Furoate/Vilanterol 100/25 mcg	Fluticasone Furoate/Vilanterol 100/25 mcg via ELLIPTA inhaler	FF/VI 100/25 mcg by inhalation OD (PM) via ELLIPTA plus placebo by inhalation BD (AM and PM) via ACCUHALER/DISKUS for 24 weeks.
Fluticasone Propionate/Salmeterol 250/50 mcg	Placebo inhalation powders via ELLIPTA inhaler	FP/Salmeterol 250/50 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.
Fluticasone Furoate/Vilanterol 100/25 mcg	Placebo inhalation powder via ACCUHALER/DISKUS inhaler	FF/VI 100/25 mcg by inhalation OD (PM) via ELLIPTA plus placebo by inhalation BD (AM and PM) via ACCUHALER/DISKUS for 24 weeks.
Fluticasone Propionate 250 mcg	Placebo inhalation powders via ELLIPTA inhaler	FP 250 mcg by inhalation BD (AM and PM) via ACCUHALER/DISKUS plus placebo by inhalation OD (PM) via ELLIPTA for 24 weeks.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population	Baseline and Week 24	FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the mixed model repeated measures (MMRM) model and least square mean and standard error were calculated. The analysis was performed on ITT Population which comprised of all participants randomized to treatment and who received at least one dose of study medication.
Change From Baseline in PM FEV1 Using Per Protocol (PP) Population	Baseline and Week 24	FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the MMRM models and least square mean and standard error were calculated. The analysis was performed on PP Population which comprised of all participants in the ITT Population who did not had any full protocol deviations.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in PM PEF	Baseline and Weeks 1-24	PEF was measured using an electric flow meter each evening. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Change From Baseline in the Percentage of Rescue-free 24-hour Periods	Baseline and Weeks 1-24	The number of inhalations of rescue medication used during the day and night were recorded by participants using an electronic diary (e-diary). A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Change From Baseline in the Percentage of Symptom-free 24-hour Periods	Baseline and Weeks 1-24	Change from Baseline in the percentage of symptom-free 24 hour period was evaluated. A 24-hour (hr) period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value.Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF)	Baseline and Weeks 1-24	PEF was measured using an electric flow meter each morning. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20	Week 24	The ACT was a five-item questionnaire developed as a measure of participant's asthma control. The percentage of participants controlled, defined as having ACT score greater than or equal to 20 at the end of Week 24 were analyzed using logistic regression model with covariates of Baseline ACT score, region, sex, age and treatment group.

Trial Locations

Locations (1)

GSK Investigational Site; 🇪🇸 Valencia, Spain