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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Placebo; Drug: FF/Vilanterol (VI; GW642444M); Drug: Fluticasone Furoate

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • GSK Investigational Site
• New Zealand
  • Wellington, New Zealand, 6021
    • GSK Investigational Site
• United Kingdom
  • London, United Kingdom, NW10 7EW
    • GSK Investigational Site
  • Manchester, United Kingdom, M23 9QZ
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 61 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Placebo Inhaler	Drug: Placebo; Placebo Inhaler
Active Comparator: inhaled corticosteroid(ICS)/long acting bronchodilator (LABA); ICS/LABA inhaler	Drug: FF/Vilanterol (VI; GW642444M); FF/VI; Other Names: FF/VI
Active Comparator: ICS; ICS inhaler	Drug: Fluticasone Furoate; FF; Other Names: FF

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Oliver A, Quinn D, Goldfrad C, van Hecke B, Ayer J, Boyce M. Combined fluticasone furoate/vilanterol reduces decline in lung function following inhaled allergen 23 h after dosing in adult asthma: a randomised, controlled trial. Clin Transl Allergy. 2012 Jun 27;2(1):11. doi: 10.1186/2045-7022-2-11.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): October 1, 2010
• Study Completion (Actual): October 1, 2010

Study Registration Dates

• First Submitted: May 20, 2010
• First Submitted That Met QC Criteria: May 20, 2010
• First Posted (Estimate): May 24, 2010

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: allergen challenge; early asthmatic response; mild asthma
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Anti-Allergic Agents; Fluticasone; Xhance
• Other Study ID Numbers: 113090 (Other Identifier: Institutional Review Board of Tungs' Taichung MetroHarbor Hospital)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Individual Participant Data Set
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Dataset Specification
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 113090
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register