Clinical trial NCT01128595: Randomised Study Comparing the Effects of Inhaled FF/GW642444M Combination, FF and GW642444M on an Allergen Induced Asthmatic Response
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: allergen challenge
early asthmatic response
mild asthma
late asthmatic response
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-05-24
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Day 21 of each treatment period (up to Study Day 197)
measure: 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
timeFrame: Day 21 of each treatment period (up to Study Day 197)
measure: 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
timeFrame: Day 21 of each treatment period (up to Study Day 197)
measure: 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
timeFrame: Day 21 of each treatment period (up to Study Day 197)
Secondary outcomes:
measure: 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
timeFrame: Day 21 of each treatment period (up to Study Day 197)
measure: Provocative Concentration of Methacholine Estimated to Result in a 20% Reduction in FEV1 (PC20) on Day 22 of Each Treatment Period
timeFrame: Day 22 of each treatment period (up to Study Day 198)
Other outcomes:
Locations:
city: Randwick
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Wellington
country: New Zealand
facility: GSK Investigational Site
city: Göteborg
country: Sweden
facility: GSK Investigational Site
city: Lund
country: Sweden
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: