Study HZA106827: 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 and fluticasone furoate inhalation powder both administered once daily in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 12 week treatment period.

Official Title
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HZA106827: A Randomised, Double-blind, Placebo-controlled (With Rescue Medication), Parallel Group Multicentre Study of Fluticasone Furoate/GW642444 Inhalation Powder and Fluticasone Furoate Inhalation Powder 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: Placebo Inhaltion Powder


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients at least 12 years of age Male and female; female subjects of childbearing potential must be willing to use birth control Pre-bronchodilator FEV1 of 40-90% predicted normal Reversibility FEV1 of at least 12% and 200mL Current asthma therapy includes inhaled corticosteroid use for at least 12 weeks prior to first visit Exclusion Criteria: History of life-threatening asthma during last 10 years Respiratory infection or oral candidiasis Asthma exacerbation requiring oral corticosteroids or that required overnight hospitalisation requiring additional asthma treatment Uncontrolled disease or clinical abnormality Allergies to study drugs or the excipients Taking another investigational medication or prohibited medication Night shift workers Current smokers or subjects with a 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 for 12 weeks | Drug: Fluticasone furoate/Vilanterol Inhalation Powder<br>* Fluticasone furoate/Vilanterol Inhalation Powder inhaled orally once daily for 12 weeks<br>|
| Experimental: Fluticasone Furoate<br>Fluticasone furoate inhalation powder once daily for 12 weeks | Drug: Fluticasone Furoate Inhalation Powder<br>* Fluticasone Furoate Inhalation Powder inhaled orally once daily for 12 weeks<br>|
| Placebo Comparator: Placebo<br>Placebo inhalation powder once daily for 12 weeks | Drug: Placebo Inhaltion Powder<br>* Placebo Inhaltion Powder inhaled orally once daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 12 | 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 clinic visit (pre-bronchodilator and pre-dose) FEV1measurement 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 through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 3. Change from Baseline was calculated as the Week 12 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, region, 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-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing m | Baseline and Week 12 | 
| Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 12 | Pulmonary function was measured by FEV1, 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 12 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 30 minutes prior to dosing at Baseline and within 5 minutes prior to dosing at Week 12) and 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 12 FEV1 value minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline FEV1, region, sex, age, and treatment group. | Baseline and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period | The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily electronic diary (eDiary). 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 12-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. | Baseline and Week 12 | 
| Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period | 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 (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 12-week Treatment Period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group. | Baseline and Week 12 | 
| Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12/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 Week 12 minus the total score at Baseline. | Baseline and Week 12/Early Withdrawal | 
| Number of Participants Who Withdrew Due to Lack of Efficacy During the 12-week Treatment Period | The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed. | From the first dose of the study medication up to Week 12/Early Withdrawal | 
| Serial FEV1 Over 0-1 Hour Post-dose at Randomization | Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Randomization. Serial FEV1 measurements after 5, 15, and 30 minutes and 1 hour post-dose were assessed. At each time point, the highest of 3 technically acceptable measurements was recorded. The analysis was performed using a repeated measures model adjusted for baseline, region, sex, age, treatment group, and planned time points. | Randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW642444, Vilanterol, Asthma, Fluticasone Furoate