Clinical Study Evaluating Safety and Efficacy of Fluticasone Furoate and Fluticasone Propionate in People With Asthma

A Randomised, Double-blind, Double-dummy, Placebo Controlled Multi-centre Study to Evaluate the Efficacy and Safety of Fluticasone Furoate Inhalation Powder and Fluticasone Propionate Inhalation Powder in the Treatment of Asthma in Adults and Adolescents Not Currently Treated With Inhaled Corticosteroids

A randomised, double-blind, double-dummy, placebo controlled multi-centre study to evaluate the efficacy and safety of fluticasone furoate inhalation powder and fluticasone propionate inhalation powder in the treatment of asthma in adults and adolescents not currently treated with inhaled corticosteroids

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone furoate 50mcg; Drug: Fluticasone propionate 100mcg; Drug: Placebo

Detailed Description

This will be a multi-centre, randomised, placebo and active controlled (with rescue medication), double-blind, double-dummy, parallel-group study. Subjects meeting all the inclusion criteria and none of the exclusion criteria during Visit 1 (Screening Visit) will enter a two week Run-in Period. 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 scores and rescue albuterol/salbutamol use. At Visit 2 (end of run-in/Randomisation Visit), subjects meeting the eligibility criteria will be randomised receive treatment with either fluticasone furoate 50 mcg once daily, fluticasone propionate 100 mcg twice daily or placebo. In addition all subjects will be supplied with albuterol/salbutamol inhalation aerosol to use as required to treat symptoms. Subjects will attend 6 on-treatment visits at Visits 3, 4, 5, 6, 7 and 8 (Weeks 2, 4, 8, 12, 18 and 24 respectively). Subjects will receive treatment for 24 weeks. 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 27 weeks (including screening, treatment and follow-up contact).

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 3

Contacts and Locations

Study Locations

• Mexico
  • Mexico city, Mexico, 04530
    • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • GSK Investigational Site
    • Zapopan, Jalisco, Mexico, 45040
      • GSK Investigational Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5644 RX
    • GSK Investigational Site
  • Hoogwoud, Netherlands, 1718 BG
    • GSK Investigational Site
  • Zutphen, Netherlands, 7207 AE
    • GSK Investigational Site
• Peru
  • Lima, Peru, Lima 1
    • GSK Investigational Site
  • Lima, Peru, Lima 29
    • GSK Investigational Site
  • Lima
    • Lima 27, Lima, Peru, Lima 27
      • GSK Investigational Site
    • San Miguel, Lima, Peru, Lima 32
      • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-046
    • GSK Investigational Site
  • Krakow, Poland, 31-159
    • GSK Investigational Site
  • Lodz, Poland, 93-329
    • GSK Investigational Site
  • Lublin, Poland, 20-552
    • GSK Investigational Site
  • Poznan, Poland, 60-693
    • GSK Investigational Site
  • Wroclaw, Poland, 50-088
    • GSK Investigational Site
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • GSK Investigational Site
  • Moscow, Russian Federation, 123182
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630087
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 194356
    • GSK Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90025
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
    • Sacramento, California, United States, 95819
      • GSK Investigational Site
    • San Jose, California, United States, 95117
      • GSK Investigational Site
  • Florida
    • Aventura, Florida, United States, 33180
      • GSK Investigational Site
    • Clearwater, Florida, United States, 33756
      • GSK Investigational Site
    • Hialeah, Florida, United States, 33016
      • GSK Investigational Site
    • Orlando, Florida, United States, 32811
      • 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
  • Missouri
    • Columbia, Missouri, United States, 65203
      • 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
    • Cincinnati, Ohio, United States, 45242
      • GSK Investigational Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Corsicana, Texas, United States, 75110
      • GSK Investigational Site
    • El Paso, Texas, United States, 79903
      • GSK Investigational Site
    • Waco, Texas, United States, 76712
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (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 a 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 during the study
• Pre-bronchodilator FEV1 of at least 60% predicted
• FEV1 reversibility of at least 12% and 200ml
• Current asthma therapy that includes a non-corticosteroid controller and/or short acting beta-agonist

Exclusion Criteria:

• History of life-threatening asthma exacerbation with the past 10 years
• Asthma exacerbation requiring oral corticosteroids within the past 3 months or overnight hospital stay within the past 6 months
• Current or recent respiratory infection or current oral candida infection
• Presence of a significant respiratory disease or other medical condition that is uncontrolled or that could affect subject safety or study outcome
• Known or suspected allergy to study medication or materials
• Taking another investigational medication or prohibited medication during the study
• Current smokers or former smokers with significant tobacco exposure
• Previous treatment with fluticasone furoate in a phase II or III study
• 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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone furoate 50 mcg; Once daily inhalation powder via Novel Dry Powder Inhaler	Drug: Fluticasone furoate 50mcg; Once daily inhalation powder via Novel Dry Powder Inhaler
Active Comparator: Fluticasone propionate 100mcg; Twice daily inhalation powder via DISKUS/ ACCUHALER	Drug: Fluticasone propionate 100mcg; Twice daily inhalation powder via DISKUS/ACCUHALER
Placebo Comparator: Placebo; Inhalation Powder via Novel Dry Powder Inhaler and DISKUS/ ACCUHALER	Drug: Placebo; Inhalation powder via Novel Dry Powder Inhaler and DISKUS?ACCUHALER

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 measurements.	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 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 During 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
Number of Participants Who Withdrew Due to Lack of Efficacy During the 24-week Treatment Period	The reason for withdrawal was lack of efficacy if a participant was withdrawn due to: clinic FEV1 falling below the FEV1 stability limit; participant experiencing at least 4 days of AM or PM PEF falling below the PEF stability limit and/or at least 3 days of >=12 inhalations/day of albuterol/salbutamol usage during the 7 days immediately preceding any contact; or the occurrence of an asthma exacerbation, defined as the deterioration of asthma requiring the use of systemic (oral, parenteral, or depot) corticosteroids for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. The FEV1 stability limit was calculated as the best pre-salbutamol/albuterol FEV1 at Visit 2 * 80%. The PEF stability limit was calculated as the mean AM PEF from the available 7 consecutive days preceding Visit 2 * 80%.	From the first dose of the study medication until Week 24/Early Withdrawal

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.

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): September 1, 2012
• Study Completion (Actual): September 1, 2012

Study Registration Dates

• First Submitted: September 15, 2011
• First Submitted That Met QC Criteria: September 15, 2011
• First Posted (Estimate): September 19, 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

• 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: 115285

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. Study Protocol
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 115285
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register