HZA113091 Efficacy and Safety of Fluticasone Furoate/Vilanterol (GW642444) in Adults and Adolescents

Study Overview
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Brief Summary
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The purpose of the study is to compare the efficacy and safety of fluticasone furoate/vilanterol (GW642444) inhalation powder administered once daily with fluticasone propionate/salmeterol administered twice daily in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24-week period.

Official Title
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A Randomised, Double-blind, Double-dummy, Parallel-group Multicentre Study to Assess Efficacy and Safety of Fluticasone Furoate/GW642444 Inhalation Powder and Fluticasone Propionate/Salmeterol Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone furoate/Vilanterol Inhalation Powder
* Drug: Fluticasone propionate/salmeterol Inhalation Powder
* Drug: Placebo (1)
* Drug: Placebo (2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical diagnosis of asthma Reversibility of at least 12% and at least 200mLs within 10-40 minutes following 2-4 inhalations of albuterol FEV1 of 40-85% predicted normal Currently using inhaled corticosteroid therapy Exclusion Criteria: History of life-threatening asthma within previous 5 years (requiring intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxic seizures) Respiratory infection or oral candidiasis Asthma exacerbation requiring oral corticosteroids or that resulted in overnight hospitalisation requiring additional asthma treatment Uncontrolled disease or clinical abnormality Allergies Taking another investigational medication or prohibited medication Night shift workers Current smokers or subjects with smoking history of at least 10 pack years

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone furoate/Vilanterol (GW642444)<br>Fluticasone furoate/vilanterol inhalation powder once daily + placebo inhalation powder twice daily for 24 weeks | Drug: Fluticasone furoate/Vilanterol Inhalation Powder<br>* Fluticasone furoate/Vilanterol Inhalation Powder inhaled orally once daily for 24 weeks<br>Drug: Placebo (2)<br>* Inhalation powder inhaled orally twice daily for 24 weeks<br>|
| Active Comparator: Fluticasone propionate/salmeterol<br>Fluticasone propionate/salmeterol inhalation powder twice daily + placebo inhalation powder once daily for 24 weeks | Drug: Fluticasone propionate/salmeterol Inhalation Powder<br>* Fluticasone propionate/salmeterol Inhalation Powder inhaled orally twice daily for 24 weeks<br>Drug: Placebo (1)<br>* Inhalation powder inhaled orally once daily for 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weighted-mean 24 Hour Serial FEV1 on Day 168/Week 24 | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, and 30 minutes (min) and at 1, 2, 3, 4, 11, 12, 12.5, 13, 14, 16, 20, 23, and 24 hours, respectively, on Day 168/Week 24. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 168/Week 24 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline FEV1, region, sex, age, and treatment. | Baseline and Day 168/Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serial FEV1 (0-24 Hours) | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second . The pre-dose FEV1 assessment and the individual serial FEV1 assessments at Day 168/Week 24 at the indicated time points (pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 11 hours, 12 hours, 12.5 hours, 13 hours, 14 hours, 16 hours, 20 hours, 23 hours, and 24 hour s) were summarized. | Day 168 | 
| Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 | Time to onset of bronchodilator effect at Day 1 is defined as the actual time during the 4-hour serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) measurements that the participant first meets or exceeds a 12% and 200 mL increase over Baseline and was derived at Day 1 only. Time to onset was calculated over 0 to 4 hours (5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours) post-dose. Participants who never exceeded a 12% and 200 mL increase over Baseline were censored at the actual time of their last FEV1 measurement. | Baseline to Day 1 | 
| Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours Post First Dose (at Randomization) | The weighted mean serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) over 0-4 hours post-dose at Baseline was derived using actual times and using the pre-dose assessment as the 0 hour measurement. Change from Baseline was calculated as the weighted mean of the 4-hour serial FEV1 measures on Day 1 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using ANCOVA with covariates of Baseline FEV1, region, sex, age, and treatment. | Baseline and Randomization | 
| Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours at Day 168 | The weighted mean serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) over 0-4 hours post-dose at Baseline and Day 168 was derived using actual times and using the pre-dose assessment as the 0 hour measurement. Change from Baseline was calculated as the weighted mean of the 4-hour serial FEV1 measures on Day 168/Week 24 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using ANCOVA with covariates of Baseline FEV1, region, sex, age, and treatment. | Baseline and Day 168 | 
| Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1 | The number of participants obtaining a >=12% and >=200 mL increase from Baseline in FEV1 (the maximal amount of air that can be forcefully exhaled in one second) was evaluated at 12-hours post-dose and at 24-hours post-dose on Day 168. | Baseline and Day 168 | 
| Change From Baseline in Trough FEV1 at Day 168 | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second . Trough FEV1 is defined as the pre-dose measurement on Day 168/Week 24. Any missing data at Day 168/Week 24 was imputed using the last observation carried forward (LOCF). Baseline was the pre-dose measurement on Day 1. Change from Baseline was calculated as the pre-dose measurement on Day 168/Week 24 minus the Baseline value. | Baseline and Day 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Salmeterol, fluticasone furoate, Vilanterol, fluticasone propionate, GW642444