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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01128569
• Other study ID #: 113090
• Status: Completed
• Phase: Phase 2
• First received: May 20, 2010
• Last updated: May 29, 2014
• Start date: January 2010
• Est. completion date: December 2010

Study information

• Verified date: September 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory AgencyGermany: Bundesinstitut für Arzneimittel und MedizinprodukteNew Zealand: Wellington Ethics CommitteeNew Zealand: Medicines and Medical Devices Safety AuthorityGermany: Berlin Ethics CommitteeUnited Kingdom: NRES Head Office, National Patient Safety AgencyUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 (LABA)/ inhaled corticosteroid (ICS) combination product on protection from allergic triggers in asthma.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 52
• Est. completion date: December 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone Furoate
FF
• FF/Vilanterol (VI; GW642444M)
FF/VI
• Placebo
Placebo Inhaler

Locations

Country	Name	City	State
Germany	GSK Investigational Site	Berlin
New Zealand	GSK Investigational Site	Wellington
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Germany,  New Zealand,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	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)	No
Secondary	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)	No
Secondary	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)	No