Evaluating the Efficacy and Safety of Fluticasone Furoate Inhalation Powder in the Treatment of Asthma in Adults and Adolescents

Study Overview
=================
Brief Summary
-----------------
A randomised, double-blind, double-dummy, placebo controlled (with rescue medication), multicenter study to evaluate the efficacy and safety of Fluticasone Furoate inhalation powder in the treatment of persistent asthma in adults and adolescents.

Detailed Description
-----------------
This is a multi-center, randomized, double-blind, double-dummy, parallel-group study to compare the efficacy and safety of Fluticasone Furoate Inhalation Powder 100mcg once daily and Fluticasone Propionate Inhalation Powder 250mcg twice daily with Placebo. Subjects will participate in the study for up to a maximum of 29 weeks (including screening, treatment and follow-up contact). The primary endpoint consists of change from baseline in clinic visit trough (pre-bronchodilator and pre-dose) FEV1 at the end of the 24 week treatment period. The nominated powered secondary endpoint is the change from baseline in the percentage of rescue-free 24 hour periods during the 24-week treatment period. Safety assessments include adverse events, oropharyngeal examinations, clinical chemistry and urine cortisol excretion. For subjects who have consented for pharmacogenetics, a blood sample will also be taken for pharmacogenetic analysis.

Official Title
-----------------
A Randomised, Double-blind, Double-dummy, Placebo Controlled (With Rescue Medication), Multicenter Study to Evaluate the Efficacy and Safety of Fluticasone Furoate Inhalation Powder in the Treatment of Persistent Asthma in Adults and Adolescents.

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: Fluticasone propionate
* Drug: Fluticasone furoate
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Outpatient at least 12 years of age Both genders; females of child bearing potential must be willing to use approved 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 4 weeks prior to first visit Exclusion Criteria: History of life threatening asthma Respiratory infection or candidiasis Asthma exacerbation within 6 months prior to first visit Concurrent respiratory disease or other disease that would confound study participation or affect subject safety Allergies to study drugs, study drug excipients, medications related to study drugs Taking another investigational medication or medication prohibited for use during this study

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone Furoate OD and Placebo BID<br>Fluticasone furoate inhalation powder once daily and placebo inhalation powder twice daily for 24 weeks | Drug: Fluticasone furoate<br>* Fluticasone furoate inhalation powder, 100 µg<br>Drug: Placebo<br>* Placebo inhalation powder<br>|
| Active Comparator: Fluticasone Propionate BID and Placebo OD<br>Fluticasone propionate inhalation powder twice daily and placebo inhalation powder once daily for 24 weeks | Drug: Fluticasone propionate<br>* Fluticasone propionate inhalation powder, 250 µg<br>Drug: Placebo<br>* Placebo inhalation powder<br>|
| Placebo Comparator: Placebo only BID<br>Placebo inhalation powder twice daily for 24 weeks | Drug: Placebo<br>* Placebo inhalation powder<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Clinic Visit Trough Evening (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 at the end of the dosing interval. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 24 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. 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 measurements. | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Percentage of Rescue-free 24-hour (hr) 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 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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | Baseline and Week 24 | 
| Mean Change From Baseline in Daily Trough Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the First 12 Weeks and 24 Weeks of the 24-week Treatment Period | PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Trough evening PEF is the PM PEF measured approximately 24 hours after the last evening administration of study drug. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 12 and Week 24 | 
| Mean Change From Baseline in Daily Morning (AM) PEF Averaged Over the First 12 Weeks and 24 Weeks of the 24-week Treatment Period | PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. 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 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 12 and Week 24 | 
| Change From Baseline in the Percentage of Symptom-free 24-hour (hr) 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 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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | Baseline and Week 24 | 
| Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24 | 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 ages 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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
fluticasone propionate, Fluticasone furoate