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

Study Overview
=================
Brief Summary
-----------------
A randomised, double-blind, multi-centre study to evaluate the efficacy and safety of two doses of inhaled fluticasone furoate in the treatment of persistent asthma in adults and adolescents currently receiving mid to high strength inhaled corticosteroids.

Detailed Description
-----------------
This will be a multi-centre, randomised, double-blind, parallel-group study. Subjects meeting all the inclusion criteria and none of the exclusion criteria during Visit 1 (screening visit) will enter a four week Run-In period during which they will remain on their baseline ICS medication. In addition, all subjects will be provided with albuterol/salbutamol for relief of asthma symptoms. Subjects failing screening will not be eligible for re-screening. During the Run-In and double-blind treatment periods subjects will maintain an electronic daily diary to record morning and evening Peak Expiratory Flow (PEF), asthma symptom score and rescue albuterol/salbutamol use. Subjects will receive a contact (Phone Contact 1/optional office visit (1b)) during Run-In to reinforce compliance with Run-In medication and diary monitoring. Those subjects who meet the eligibility criteria at the end of the Run-In period will be stratified in an approximately 1:1 ratio according to their baseline FEV1 as a percentage of predicted normal - one stratum for those with FEV1 percent predicted ≥40% to ≤65% and one for those with FEV1 percent predicted >65% to ≤90%. Once stratified, subjects will be randomised to one of the following treatments and enter into a 24 week double-blind treatment period:1) Fluticasone furoate 100mcg once daily in the evening or 2) Fluticasone furoate 200mcg once daily in the evening. Subjects will then attend 6 on-treatment visits at Visits 3, 4, 5, 6, 7 and 8 (Weeks 2, 4, 8, 12, 18 and 24 respectively). All visits including Visit 1 must be conducted in the evening between 5 PM and 11 PM. Subjects will receive treatment for 24 weeks. Twenty four hour urinary cortisol assessments will be collected at the end of Run-In (Visit 2) and at end of treatment (Visit 8) visits. A follow-up contact will be performed 1-week after completing study medication (Visit 9). Subjects will participate in the study for up to a maximum of 29 weeks (including screening, treatment and follow-up contact). In addition, partially used NDPIs will be collected in a subset of subjects. For subjects who have consented for pharmacogenetics, a blood sample will also be taken for pharmacogenetic analysis.

Official Title
-----------------
A Randomised, Double-blind, Multi-centre Study to Evaluate the Efficacy and Safety of Inhaled Fluticasone Furoate in the Treatment of Persistent Asthma in Adults and Adolescents Currently Receiving Mid to High Strength Inhaled Corticosteroids.

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

Intervention / Treatment
-----------------
* Drug: fluticasone furoate
* Drug: albuterol/salbutamol


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Signed informed consent Outpatient at least 12 years of age with diagnosis of asthma at least 12 weeks prior to first visit Both genders; females of child bearing potential must be willing to use appropriate contraception Pre-bronchodilator FEV1 of 40-90% predicted Reversibility FEV1 of at least 12% and 200mLs Current asthma therapy that includes inhaled corticosteroid for at least 4 weeks prior to first visit Exclusion Criteria: History of life threatening asthma Respiratory infection or candidiasis Asthma exacerbation requiring OCS within last 4 weeks or overnight hospital stay within the last 3 months Concurrent respiratory disease or other disease that would confound study participation of 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 the study Previous treatment with FF or FF/VI in a phase II or III study Night shift workers Children in care

Ages Eligible for Study
-----------------
Minimum Age: 12 Years
Maximum Age: 100 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: FF 100mcg once daily<br>Inhaled corticosteroid (ICS) | Drug: fluticasone furoate<br>* Inhaled corticosteroid<br>Drug: albuterol/salbutamol<br>* Provided as rescue relief of asthma symptoms<br>|
| Experimental: FF 200mcg once daily<br>Inhaled corticosteroid | Drug: fluticasone furoate<br>* Inhaled corticosteroid<br>Drug: albuterol/salbutamol<br>* Provided as rescue relief of asthma symptoms<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Clinic Visit 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. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 24 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were 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, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value. | 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 Over 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). 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. A 24-hour period was considered as missing if both day time and night time values were missing or if one of the day time or night time values were missing and the other value indicated no use of rescue medication. The Baseline value is the average of the values over 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. | From Baseline up to Week 24 | 
| Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over 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 average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 24 | 
| Change From Baseline in Daily Morning (AM) PEF Averaged Over 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 average of the values of 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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. | From Baseline up to Week 24 | 
| Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over the 24-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 period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. A 24-hour period was considered as missing if both the day time and night time data were missing or if one was symptom-free but the other was missing. The Baseline value was the average of the values of 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. | From Baseline up to Week 24 | 

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