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

NCT01128595 | Completed Phase 2 Results

• 1 other identifier: 113126
• Study Type: interventional
• Target: 27
• Locations: 3 countries
• Sites: 4

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

Conditions

Asthma

Keywords

allergen challenge; early asthmatic response; mild asthma; late asthmatic response

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (2)

• 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

  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

  Day 22 of each treatment period (up to Study Day 198)

Study Arms (4)

ICS

ACTIVE COMPARATOR

Drug: Fluticasone Furoate

ICS/LABA

ACTIVE COMPARATOR

Drug: FF/GW642444M

LABA

ACTIVE COMPARATOR

Drug: GW642444M

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

FF/GW642444M DRUG

ICS/LABA

GW642444M DRUG

LABA

Fluticasone Furoate DRUG

ICS

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (4)

GSK Investigational Site

Randwick, New South Wales, 2031, Australia

Location

GSK Investigational Site

Wellington, 6021, New Zealand

Location

GSK Investigational Site

Gothenburg, SE-413 45, Sweden

Location

GSK Investigational Site

Lund, SE-221 85, Sweden

Location

Related 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.

MeSH Terms

Conditions

Asthma

Interventions

fluticasone furoate

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 20, 2010
• First Posted: May 24, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: January 18, 2017
• Results First Posted: August 9, 2013

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

NZ (1); SE (2); AU (1)