Study HZA106829: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics

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 each evening with fluticasone furoate inhalation powder administered alone once daily each evening 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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HZA106829: A Randomised, Double-blind, Parallel Group, Multicentre Study of Fluticasone Furoate/GW642444 Inhalation Powder, Fluticasone Furoate Inhalation Powder Alone, and Fluticasone Propionate Alone 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 Furoate Inhalation Powder
* Drug: Fluticasone Propionate Inhalation Powder
* Other: Placebo Inhalation Powder 1
* Other: Placebo Inhalation Powder 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatient at least 12 years of age Both genders; females of childbearing potential must be willing to use birth control method Pre-bronchodilator FEV1 of 40-90% predicted Reversibility FEV1 of at least 12% and 200mls Current asthma therapy that includes an inhaled corticosteroid for at least 12 weeks prior to first visit Exclusion Criteria: History of life-threatening asthma Respiratory infection or oral candidiasis Asthma exacerbation within 12 weeks Concurrent respiratory disease or other disease that would confound study participation or affect subject safety Allergies to study drugs, study drugs' excipients, medications related to study drugs Taking another investigational medication or medication prohibited for use during this study

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<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>Other: Placebo Inhalation Powder 2<br>* Placebo in Diskus inhaler twice daily<br>|
| Active Comparator: Fluticasone Furoate<br>Fluticasone furoate inhalation powder once daily + Placebo inhalation powder twice daily for 24 weeks | Drug: Fluticasone Furoate Inhalation Powder<br>* Fluticasone furoate inhalation powder inhaled orally once daily for 24 weeks<br>Other: Placebo Inhalation Powder 2<br>* Placebo in Diskus inhaler twice daily<br>|
| Active Comparator: Fluticasone Propionate<br>Fluticasone propionate inhalation powder twice daily + Placebo inhalation powder once daily for 24 weeks | Drug: Fluticasone Propionate Inhalation Powder<br>* Fluticasone propionate inhalation powder inhaled orally twice daily for 24 weeks<br>Other: Placebo Inhalation Powder 1<br>* Placebo in novel dry powder inhaler once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 24-week Treatment Period | 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 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the clinic visit while still on treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline (BL) through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. BL was the pre-dose value obtained at Visit 3. Change from BL was calculated as the Week 24 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group.The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement at scheduled clinic visits was used to impute the missing measurements. | Baseline and Week 24 | 
| Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 24 | FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 24 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and the post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Percentage of Rescue-free and Symptom-free 24-hour Periods at the End of the 24-week Treatment Period | The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). Similarly, asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication/symptoms was considered to be rescue free/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. | Baseline and Week 24 | 
| Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24/Early Withdrawal | The AQLQ is a disease-specific, self-administered quality of life questionnaire used to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ for 12 years and older (AQLQ [+12]) is a modified version of the AQLQ for use in asthma patients between the age of 12 and 70. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). For the 32 items on the questionnaire, the response format consists of a seven-point scale, where a value of 1 indicates total impairment and a value of 7 indicates no impairment. The AQLQ total score is defined as the average of the scores from all 32 questions; thus, the total score ranges from 1 (indicates total impairment) to 7 (indicates no impairment). Baseline was the total score obtained at Visit 3. Change from Baseline was calculated as the total score at Weeks 12 and 24 minus the total score at Baseline. | Baseline, Week 12, and Week 24/Early Withdrawal | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluticasone propionate, asthma, vilanterol, GW642444, Fluticasone furoate