Randomised Study Comparing the Effects of Inhaled Fluticasone Furoate (FF)/Vilanterol (VI; GW642444M) Combination and FF on an Allergen Induced Asthmatic Response

Study Overview
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Brief Summary
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We propose to use an inhaled allergen challenge model to explore the individual contributions of the components of a novel long-acting beta agonist (LABA)/ inhaled corticosteroid (ICS) combination product on protection from allergic triggers in asthma.

Official Title
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A Randomised, Double-blind, Placebo-controlled, Three-way Crossover, Repeat Dose Pilot Study Comparing the Effect of Inhaled Fluticasone Furoate/GW642444M Combination and Fluticasone Furoate on the Allergen-induced Early Asthmatic Response in Subjects With Mild Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Fluticasone Furoate
* Drug: FF/Vilanterol (VI; GW642444M)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Body mass index within the range 18.5-35.0 kilograms/metre2 (kg/m2). Females of non-child bearing potential. Documented history of bronchial asthma, first diagnosed at least 6 months prior to the screening visit and currently being treated only with intermittent short-acting beta -agonist therapy by inhalation Pre-bronchodilator FEV1 >70% of predicted at screening Subjects who are current non-smokers Methacholine challenge PC20 < 8 mg/mL at screening Screening allergen challenge demonstrates that the subject experiences an early asthmatic response Exclusion Criteria: Current or chronic history of liver disease, or known hepatic or biliary abnormalities Subject is hypertensive at screening Respiratory tract infection and/or exacerbation of asthma within 4 weeks prior to the first dose of study medication. History of life-threatening asthma Symptomatic with hay fever at screening or predicted to have symptomatic hayfever Unable to abstain from short acting beta agonists Unable to abstain from antihistamines Unable to abstain from other medications including non-steroidal anti-inflammatory drugs (NSAIDs), anti-depressant drugs, anti-asthma anti-rhinitis or hay fever medication The subject has participated in a study with a new molecular entity during the previous 3 months or has participated in 4 or more clinical studies in the previous 12 months undergoing allergen desensitisation therapy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Inhaler | Drug: Placebo<br>* Placebo Inhaler<br>|
| Active Comparator: inhaled corticosteroid(ICS)/long acting bronchodilator (LABA)<br>ICS/LABA inhaler | Drug: FF/Vilanterol (VI; GW642444M)<br>* FF/VI<br>* Other names: FF/VI;|
| Active Comparator: ICS<br>ICS inhaler | Drug: Fluticasone Furoate<br>* FF<br>* Other names: FF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Weighted Mean Change From Baseline in Forced Expiratory Volume in One Second (FEV1) Between 0-2 Hours, Following the 22-23 Hour Post-treatment Allergen Challenge on Day 29 of Each 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. Participants (par.) were exposed to an allergen (administered by inhalation) 22-23 hours after dosing on Day 28. FEV1 was measured 5 minutes (min), 10 min, 15 min, 20 min, 30 min, and 45 min and 1 hour, 1.5 hours, and 2 hours post-allergen challenge on Day 29. Immediately prior to the exposure of allergen and starting at 2 minutes after inhalation of saline, 3 single measurements of FEV1 were recorded at 1-minute intervals, and the best was taken as the post-saline value. The FEV1 weighted mean was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. Weighted mean change from Baseline is calculated as the weighted mean FEV1 value on Day 29 minus the Baseline value. The Baseline FEV1 value was the post-saline value on Day 29. | Baseline and Day 29 of each treatment period (up to Study Day 197) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Percent Decrease From Baseline in FEV1 Between 0 2 Hour, Following the 22-23 Hour Post-treatment Allergen Challenge on Day 29 of Each 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. Participants were exposed to an allergen 22-23 hours after dosing on Day 28. Immediately prior to the exposure of allergen and starting at 2 minutes (min) after inhalation of saline, 3 single measurements of FEV1were recorded at 1-min intervals, and the best was taken as the post-saline value. The maximum change (i.e., drop in FEV1) from post-saline Baseline (BL) is defined by ordering all of the change from BL values for the 5 min, 10 min, 15 min, 20 min, 30 min, and 45 min and the 1 hour, 1.5 hours, and 2 hours post-allergen challenge and selecting the largest change (i.e., drop in FEV1) from the BL value. If there were no negative change values, indicating a worse FEV1 value as compared to the BL value, the smallest change in FEV1, indicating an improvement from the BL value, was selected. The BL FEV1 value was the post-saline value on Day 29. | Baseline and Day 29 of each treatment period (up to Study Day 197) | 
| Minimum FEV1 Absolute Change From Baseline Between 0-2 Hour, Following the 22-23 Hour Post-treatment Allergen Challenge on Day 29 of Each 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. Participants were exposed to an allergen 22-23 hours after dosing on Day 28. Immediately prior to the exposure of allergen and starting at 2 minutes after inhalation of saline, 3 single measurements of FEV1were recorded at 1-minute intervals, and the best was taken as the post-saline value. The minimum FEV1 over 0-2 hours post-allergen challenge (PAC) (minimum early asthmatic response) was the minimum value of all of the PAC time points up to and including 2 hours PAC (i.e., minimum over 5 minutes (min), 10 min, 15 min, 20 min, 30 min, and 45 min and 1 hour, 1.5 hours, and 2 hours). Change from Baseline was calculated using the post-saline FEV1 on Day 29 as Baseline. Minimum FEV1 absolute change from Baseline between 0-2 hour, following the 22-23 hour post-treatment allergen challenge was calculated as the minimum change value on Day 29 minus the Baseline value | Baseline and Day 29 of each treatment period (up to Study Day 197) | 
| Number of Participants With Treatment-emergent Adverse Events (AEs) | The number of participants with treatment-emergent AEs was measured. A treatment-emergent adverse event is defined as any event not present prior to the initiation of the treatments, or any event already present that worsens in either intensity of frequency following exposure to the treatments. | From the start of study medication until Follow-up/Early Withdrawal (up to 197 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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mild asthma, allergen challenge, early asthmatic response