Randomised Study Comparing the Effects of Inhaled FF/GW642444M Combination, FF and GW642444M on an Allergen Induced Asthmatic Response

A Randomised, Double-blind, Placebo-controlled, Four-way Crossover, Repeat Dose Study Comparing the Effect of Inhaled Fluticasone Furoate/GW642444M Combination, GW642444M and Fluticasone Furoate on the Allergen-induced 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/ inhaled corticosteroid combination product and its components on protection from allergic triggers in asthma

Study Overview

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

Detailed Description

Asthma is an increasingly common disease and is essentially caused by an allergic type of reaction of the immune system. Airways of the lungs become inflamed and narrow as a result of a reaction to triggers like chemicals (house-hold cleaning products, pollution) and allergens (house dust mite and cat or dog fur). The airways become blocked, causing shortness of breath and wheezing. The purpose of this study is to find out more information about how effective the study drugs are at protecting the lungs against allergic triggers of asthma. There are three study drugs being investigated in this study: fluticasone furoate on its own, GW642444M on its own and a combination of fluticasone furoate (FF) and GW642444M.

FF is a corticosteroid that is being developed by for the treatment of asthma. A nasal spray formulation of FF has been approved for marketing in the USA, Europe and Japan for the treatment of hayfever (rhinitis) but the dry powder formulation used in this study is not yet approved.

GW642444M is a long-acting beta2-agonist being developed by GSK for the treatment of chronic obstructive pulmonary disease (COPD). It works by acting on cells in the lungs, causing some of the muscles around the lungs to relax and open up better (bronchodilation), making breathing easier. The combination of FF/GW642444M is being developed as a once-daily treatment for both asthma and COPD.

Study treatment will be taken for 21 days in each period (4 treatment periods: FF alone, GW642444M alone, FF/GW64244M combination and placebo) and each subject will receive all treatments. On D21 subjects will undergo an allergen challenge, followed by a methacholine challenge on D22. The washout between treatment periods will be 21-35 days.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • GSK Investigational Site
• New Zealand
  • Wellington, New Zealand, 6021
    • GSK Investigational Site
• Sweden
  • Göteborg, Sweden, SE-413 45
    • GSK Investigational Site
  • Lund, Sweden, SE-221 85
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 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
• Masking: DOUBLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Placebo
ACTIVE_COMPARATOR: ICS	Drug: Fluticasone Furoate
ACTIVE_COMPARATOR: ICS/LABA	Drug: FF/GW642444M
ACTIVE_COMPARATOR: LABA	Drug: GW642444M

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Late Asthmatic Response (LAR): Absolute Change From Saline in Minimum FEV1 Between 4-10 Hours (Hrs) Following the 1-hr Post-treatment Allergen Challenge on Day 21 of Each Treatment Period	Forced expiratory volume in one second (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 (administered by inhalation) 1 hr after dosing on Day 21. Minimum FEV1 over 4-10 hours post-allergen challenge (minimum LAR) is the minimum value of all of the post-saline time points between 4 and 10 hrs post-allergen challenge, inclusive of the 4 hr and 10 hr timepoints (i.e., minimum over 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs). Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.	Day 21 of each treatment period (up to Study Day 197)
LAR: Absolute Change From Saline in Weighted Mean (WM) FEV1 Between 4-10 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 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 1 hour after dosing on Day 21. LAR FEV1 was measured 4 hrs, 4.5 hrs, 5 hrs, 5.5 hrs, 6 hrs, 6.5 hrs, 7 hrs, 7.5 hrs, 8 hrs, 8.5 hrs, 9 hrs, 9.5 hrs, and 10 hrs post-allergen challenge on Day 21. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.	Day 21 of each treatment period (up to Study Day 197)
Early Asthmatic Response (EAR): Absolute Change From Saline in Minimum FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 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 1 hr after dosing on Day 21. Minimum FEV1 over 0-2 hrs post-allergen challenge (Minimum EAR) is the minimum value of all of the post-allergen challenge timepoints up to and including 2 hours post-allergen challenge (i.e., minimum over 5 minutes (min), 10 min, 15 min, 20 min, 30 min, 45 min and 1 hr, 1.5 hrs, and 2 hrs. Absolute change from saline in minimum FEV1 was calculated as the minimum FEV1 minus the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value. Least squares means were obtained by adjusting for period and participant and period Baselines.	Day 21 of each treatment period (up to Study Day 197)
EAR: Absolute Change From Saline in Weighted Mean FEV1 Between 0-2 Hrs Following the 1-hr Post-treatment Allergen Challenge on Day 21 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 1 hr after dosing on Day 21. The EAR FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Least squares means were obtained by adjusting for period and participant and period Baselines. Absolute change from saline in WM FEV1 was calculated as the area under the curve divided by the relevant time interval and subtracting the saline FEV1 value. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value.	Day 21 of each treatment period (up to Study Day 197)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum Percent Change From Saline in FEV1 Between 0-2 Hrs, Following the 1-hr Post-treatment Allergen Challenge on Day 21 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 1 hr after dosing on Day 21. FEV1 was measured 0 minutes (min), 5 min, 10 min, 15 min, 20 min, 30 min, 45 min, 1 hr, 1.5 hrs, and 2 hrs post-allergen challenge on Day 21. Maximum percent change was calculated as the minimum FEV1 minus the saline FEV1 value divided by the saline FEV1 multiplied by 100. After inhalation of saline, 3 single measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline FEV1 value.	Day 21 of each treatment period (up to Study Day 197)
Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 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 inhaled doubling increments of methacholine until a >=20% fall in FEV1 from the saline value was achieved. After inhalation of saline, 3 measurements of FEV1 were recorded; the maximum FEV1 value was taken as the saline value.	Day 22 of each treatment period (up to Study Day 198)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

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: May 1, 2010
• Primary Completion (ACTUAL): May 1, 2011
• Study Completion (ACTUAL): May 1, 2011

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; late asthmatic response
• 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: 113126

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. Informed Consent Form
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Dataset Specification
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 113126
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register