Evaluating the Efficacy and Safety of Fluticasone Furoate in the Treatment of Asthma in Adults and Adolescents

A Randomised, Double-blind, Multi-centre Study to Evaluate the Efficacy and Safety of Inhaled Fluticasone Furoate in the Treatment of Persistent Asthma in Adults and Adolescents Currently Receiving Mid to High Strength Inhaled Corticosteroids.

A randomised, double-blind, multi-centre study to evaluate the efficacy and safety of two doses of inhaled fluticasone furoate in the treatment of persistent asthma in adults and adolescents currently receiving mid to high strength inhaled corticosteroids.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: fluticasone furoate; Drug: albuterol/salbutamol

Detailed Description

This will be a multi-centre, randomised, double-blind, parallel-group study. Subjects meeting all the inclusion criteria and none of the exclusion criteria during Visit 1 (screening visit) will enter a four week Run-In period during which they will remain on their baseline ICS medication. In addition, all subjects will be provided with albuterol/salbutamol for relief of asthma symptoms. Subjects failing screening will not be eligible for re-screening. During the Run-In and double-blind treatment periods subjects will maintain an electronic daily diary to record morning and evening Peak Expiratory Flow (PEF), asthma symptom score and rescue albuterol/salbutamol use. Subjects will receive a contact (Phone Contact 1/optional office visit (1b)) during Run-In to reinforce compliance with Run-In medication and diary monitoring. Those subjects who meet the eligibility criteria at the end of the Run-In period will be stratified in an approximately 1:1 ratio according to their baseline FEV1 as a percentage of predicted normal - one stratum for those with FEV1 percent predicted ≥40% to ≤65% and one for those with FEV1 percent predicted >65% to ≤90%. Once stratified, subjects will be randomised to one of the following treatments and enter into a 24 week double-blind treatment period:1) Fluticasone furoate 100mcg once daily in the evening or 2) Fluticasone furoate 200mcg once daily in the evening.

Subjects will then attend 6 on-treatment visits at Visits 3, 4, 5, 6, 7 and 8 (Weeks 2, 4, 8, 12, 18 and 24 respectively). All visits including Visit 1 must be conducted in the evening between 5 PM and 11 PM. Subjects will receive treatment for 24 weeks. Twenty four hour urinary cortisol assessments will be collected at the end of Run-In (Visit 2) and at end of treatment (Visit 8) visits. A follow-up contact will be performed 1-week after completing study medication (Visit 9). Subjects will participate in the study for up to a maximum of 29 weeks (including screening, treatment and follow-up contact). In addition, partially used NDPIs will be collected in a subset of subjects. For subjects who have consented for pharmacogenetics, a blood sample will also be taken for pharmacogenetic analysis.

• Study Type: Interventional
• Enrollment (Actual): 238
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Ciudad Autonoma de Buenos Aires, Argentina, C1425BEN
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1121ABE
    • GSK Investigational Site
  • Mendoza, Argentina, M5500CCG
    • GSK Investigational Site
  • San Miguel de Tucumán, Argentina, 4000
    • GSK Investigational Site
• Chile
  • Región Metro De Santiago
    • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500800
      • GSK Investigational Site
  • Valparaíso
    • Valparaiso, Valparaíso, Chile, 2341131
      • GSK Investigational Site
• France
  • Aigrefeuille Sur Maine, France, 44140
    • GSK Investigational Site
  • Bourg Des Comptes, France, 35890
    • GSK Investigational Site
  • Chalons en Champagne, France, 51000
    • GSK Investigational Site
  • Laon, France, 02000
    • GSK Investigational Site
  • Nantes, France, 44300
    • GSK Investigational Site
  • Vannes, France, 56000
    • GSK Investigational Site
• Mexico
  • Mexico City, Mexico, 07760
    • GSK Investigational Site
  • Tabasco
    • Villahermosa, Tabasco, Mexico, 86100
      • GSK Investigational Site
• Russian Federation
  • Belgorod, Russian Federation, 308007
    • GSK Investigational Site
  • Kazan, Russian Federation, 420015
    • GSK Investigational Site
  • Novokuznetsk, Russian Federation, 654063
    • GSK Investigational Site
  • Penza, Russian Federation, 440067
    • GSK Investigational Site
  • Pyatigorsk, Russian Federation, 357538
    • GSK Investigational Site
• United States
  • California
    • Long Beach, California, United States, 90808
      • GSK Investigational Site
    • Newport Beach, California, United States, 92663
      • GSK Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80907
      • GSK Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • GSK Investigational Site
  • Georgia
    • Albany, Georgia, United States, 31707
      • GSK Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
    • Sunset, Louisiana, United States, 70584
      • GSK Investigational Site
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • GSK Investigational Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55441
      • GSK Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • GSK Investigational Site
  • New Jersey
    • Brick, New Jersey, United States, 08724
      • GSK Investigational Site
  • New York
    • Utica, New York, United States, 13502
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45242
      • GSK Investigational Site
    • Toledo, Ohio, United States, 43617
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 100 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Outpatient at least 12 years of age with diagnosis of asthma at least 12 weeks prior to first visit
• Both genders; females of child bearing potential must be willing to use appropriate contraception
• Pre-bronchodilator FEV1 of 40-90% predicted
• Reversibility FEV1 of at least 12% and 200mLs
• Current asthma therapy that includes inhaled corticosteroid for at least 4 weeks prior to first visit

Exclusion Criteria:

• History of life threatening asthma
• Respiratory infection or candidiasis
• Asthma exacerbation requiring OCS within last 4 weeks or overnight hospital stay within the last 3 months
• Concurrent respiratory disease or other disease that would confound study participation of affect subject safety
• Allergies to study drugs, study drug excipients, medications related to study drugs
• Taking another investigational medication or medication prohibited for use during the study
• Previous treatment with FF or FF/VI in a phase II or III study
• Night shift workers
• Children in care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FF 100mcg once daily; Inhaled corticosteroid (ICS)	Drug: fluticasone furoate; Inhaled corticosteroid; Drug: albuterol/salbutamol; Provided as rescue relief of asthma symptoms
Experimental: FF 200mcg once daily; Inhaled corticosteroid	Drug: fluticasone furoate; Inhaled corticosteroid; Drug: albuterol/salbutamol; Provided as rescue relief of asthma symptoms

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinic Visit Evening (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at the End of the 24-week 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. Evening clinic visit FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the Week 24 clinic visit. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 were measured electronically by spirometry in the evening at the Baseline through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 24 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing, pre-dose, post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing value.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods Over the 24-week Treatment Period	The number of inhalations of rescue bronchodilator, albuterol/salbutamol inhalation aerosol, used during the day and night was recorded by the participants in a daily electronic diary (eDiary). A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. A 24-hour period was considered as missing if both day time and night time values were missing or if one of the day time or night time values were missing and the other value indicated no use of rescue medication. The Baseline value is the average of the values over the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.	From Baseline up to Week 24
Change From Baseline in Daily Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the 24-week Treatment Period	PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough PM PEF over the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.	From Baseline up to Week 24
Change From Baseline in Daily Morning (AM) PEF Averaged Over the 24-week Treatment Period	PEF is a measure of lung function and is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. PEF was measured by the participants using a hand-held electronic peak flow meter each morning and evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use. Change from Baseline (defined as the average of the values of the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.	From Baseline up to Week 24
Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods Over the 24-week Treatment Period	Asthma symptoms were recorded in a daily eDairy by the participants every day in the morning and evening before taking any rescue or study medication and before the peak expiratory flow measurement. A 24-hour period in which a participant's responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. A 24-hour period was considered as missing if both the day time and night time data were missing or if one was symptom-free but the other was missing. The Baseline value was the average of the values of the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week Treatment Period minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.	From Baseline up to Week 24

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• O'Byrne PM, Jacques L, Goldfrad C, Kwon N, Perrio M, Yates LJ, Busse WW. Integrated safety and efficacy analysis of once-daily fluticasone furoate for the treatment of asthma. Respir Res. 2016 Nov 24;17(1):157. doi: 10.1186/s12931-016-0473-x.
• Svedsater H, Jacques L, Goldfrad C, Bleecker ER. Ease of use of the ELLIPTA dry powder inhaler: data from three randomised controlled trials in patients with asthma. NPJ Prim Care Respir Med. 2014 Jun 26;24:14019. doi: 10.1038/npjpcrm.2014.19. No abstract available.
• Svedsater H, Dale P, Garrill K, Walker R, Woepse MW. Qualitative assessment of attributes and ease of use of the ELLIPTA dry powder inhaler for delivery of maintenance therapy for asthma and COPD. BMC Pulm Med. 2013 Dec 7;13:72. doi: 10.1186/1471-2466-13-72.
• Woodcock A, Lotvall J, Busse WW, Bateman ED, Stone S, Ellsworth A, Jacques L. Efficacy and safety of fluticasone furoate 100 mug and 200 mug once daily in the treatment of moderate-severe asthma in adults and adolescents: a 24-week randomised study. BMC Pulm Med. 2014 Jul 9;14:113. doi: 10.1186/1471-2466-14-113.

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: September 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): October 1, 2012

Study Registration Dates

• First Submitted: August 25, 2011
• First Submitted That Met QC Criteria: September 8, 2011
• First Posted (Estimate): September 12, 2011

Study Record Updates

• Last Update Posted (Estimate): January 9, 2017
• Last Update Submitted That Met QC Criteria: November 18, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: fluticasone furoate
• 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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Adrenergic Agonists; Dermatologic Agents; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Reproductive Control Agents; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Fluticasone; Xhance; Albuterol
• Other Study ID Numbers: 114496

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. Annotated Case Report Form
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Individual Participant Data Set
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Clinical Study Report
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Dataset Specification
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 114496
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register