Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate in People With Asthma

Study Overview
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Brief Summary
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A randomised, double-blind, placebo-controlled (with rescue medication), multi-centre study to evaluate the efficacy and safety of inhaled fluticasone furoate in the treatment of persistent asthma in adults and adolescents not currently receiving inhaled corticosteroids

Detailed Description
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This will be a multi-centre, randomised, placebo controlled (with rescue medication), 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 two week Run-in Period. 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. At Visit 2 (end of run-in/Randomisation Visit), subjects meeting the eligibility criteria will be randomised to either inhaled Fluticasone Furoate 50 mcg or inhaled placebo. In addition all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as required to treat symptoms. Subjects will attend 4 on-treatment visits at Visits 3, 4, 5, and 6 (Weeks 2, 4, 8 and 12 respectively). Subjects will receive treatment for 84 days (12 weeks). A follow-up contact will be performed 1-week after completing study medication (Visit 7). Subjects will participate in the study for up to a maximum of 15 weeks (including screening, treatment and follow-up contact).

Official Title
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A Randomised, Double-blind, Placebo-controlled (With Rescue Medication), Multi-centre Study to Evaluate the Efficacy and Safety of Inhaled Fluticasone Furoate in the Treatment of Persistent Asthma in Adults and Adolescents Not Currently Receiving Inhaled Corticosteroids

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone furoate 50mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Outpatient at least 12 years of age with diagnosis of asthma at least 12 weeks before first visit Both genders; females of child bearing potential must be willing to use appropriate contraception during the study Pre-bronchodilator FEV1 of at least 60% predicted FEV1 reversibility of at least 12% and 200mls Current asthma therapy that includes a non-corticosteroid controller and/or short-acting beta agonist Exclusion Criteria: History of life-threatening asthma exacerbation within the past 10 years Asthma exacerbation requiring treatment with oral corticosteroids within the last 3 months or that required overnight hospital stay within 6 months Current or recent respiratory infection or current oral candida infection Presence of another significant respiratory disease or medical condition that is not controlled or that could affect subject safety or study outcome Known or suspected allergy to study drug or materials Taking another investigational medication or prohibited medication during the study Previous treatment with inhaled fluticasone furoate in a phase II or III study Current smokers or former smokers with significant tobacco exposure Children in Care

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fluticasone furoate 50mcg<br>Inhalation powder delivered by Novel Dry Powder Inhaler | Drug: Fluticasone furoate 50mcg<br>* Inhalation powder delivered by Novel Dry Powder Inhaler<br>|
| Placebo Comparator: Placebo<br>Inhalation powder delivered by Novel Dry Powder Inhaler | Drug: Placebo<br>* Inhalation powder delivered by Novel Dry Powder Inhaler<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 Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 12-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 12 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were 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 2. Change from Baseline was calculated as the Week 12 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 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 12-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 12 | 
| Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 12-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 12-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 12 | 
| Change From Baseline in Daily Morning (AM) PEF Averaged Over the 12-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 12-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 12 | 
| Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over 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 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 12-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 12 | 
| Number of Participants Who Withdrew Due to a Lack of Efficacy During the 12-week Treatment Period | The reason for withdrawal was lack of efficacy if a participant was withdrawn due to: clinic FEV1 falling below the FEV1 stability limit; participant experiencing at least 4 days of AM or PM PEF falling below the PEF stability limit and/or at least 3 days of >=12 inhalations/day of albuterol/salbutamol usage during the 7 days immediately preceding any contact; or the occurrence of an asthma exacerbation, defined as the deterioration of asthma requiring the use of systemic (oral, parenteral, or depot) corticosteroids for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The FEV1 stability limit was calculated as the best pre-salbutamol/albuterol FEV1 at Visit 2 * 80%. The PEF stability limit was calculated as the mean AM PEF from the available 7 consecutive days preceding Visit 2 * 80%. | From the first dose of the study medication until Week 12/Early Withdrawal |