Asthma Exacerbation Study

A Long-Term, Randomized, Double-Blind, Parallel Group Study of Fluticasone Furoate/GW642444 Inhalation Powder Once-Daily and Fluticasone Furoate Inhalation Powder Once-Daily in Subjects With Asthma

This study will establish the safety as well as demonstrate benefit of the addition of a LABA to an ICS by utilizing an endpoint (time to first severe asthma exacerbation) that informs on both safety and efficacy.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone Furoate/GW642444; Drug: Fluticasone furoate

• Study Type: Interventional
• Enrollment (Actual): 2020
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424BSF
    • GSK Investigational Site
  • 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
  • Tucuman, Argentina, 4000
    • GSK Investigational Site
  • Buenos Aires
    • Quilmes, Buenos Aires, Argentina, B1878FNR
      • GSK Investigational Site
  • Entre Ríos
    • Parana, Entre Ríos, Argentina, E3100BHK
      • GSK Investigational Site
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000DSR
      • GSK Investigational Site
• Australia
  • Australian Capital Territory
    • Garran, Australian Capital Territory, Australia, 2606
      • GSK Investigational Site
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • GSK Investigational Site
    • Hornsby, New South Wales, Australia, 2077
      • GSK Investigational Site
  • Queensland
    • Auchenflower, Queensland, Australia, 4066
      • GSK Investigational Site
  • South Australia
    • Toorak Gardens, South Australia, Australia, 5065
      • GSK Investigational Site
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • GSK Investigational Site
• Germany
  • Berlin, Germany, 13086
    • GSK Investigational Site
  • Hamburg, Germany, 20357
    • GSK Investigational Site
  • Hamburg, Germany, 22335
    • GSK Investigational Site
  • Hamburg, Germany, 22299
    • GSK Investigational Site
  • Hamburg, Germany, 22767
    • GSK Investigational Site
  • Baden-Wuerttemberg
    • Deggingen, Baden-Wuerttemberg, Germany, 73326
      • GSK Investigational Site
    • Weinheim, Baden-Wuerttemberg, Germany, 69469
      • GSK Investigational Site
  • Bayern
    • Aschaffenburg, Bayern, Germany, 63739
      • GSK Investigational Site
    • Grossheirath, Bayern, Germany, 96269
      • GSK Investigational Site
    • Vilshofen, Bayern, Germany, 94474
      • GSK Investigational Site
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03050
      • GSK Investigational Site
    • Potsdam, Brandenburg, Germany, 14469
      • GSK Investigational Site
    • Ruedersdorf, Brandenburg, Germany, 15562
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60596
      • GSK Investigational Site
    • Frankfurt, Hessen, Germany, 60389
      • GSK Investigational Site
    • Marburg, Hessen, Germany, 35037
      • GSK Investigational Site
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44787
      • GSK Investigational Site
    • Dortmund, Nordrhein-Westfalen, Germany, 44263
      • GSK Investigational Site
    • Essen, Nordrhein-Westfalen, Germany, 45359
      • GSK Investigational Site
    • Gelsenkirchen, Nordrhein-Westfalen, Germany, 45879
      • GSK Investigational Site
    • Goch, Nordrhein-Westfalen, Germany, 47574
      • GSK Investigational Site
    • Solingen, Nordrhein-Westfalen, Germany, 42651
      • GSK Investigational Site
    • Witten, Nordrhein-Westfalen, Germany, 58452
      • GSK Investigational Site
  • Rheinland-Pfalz
    • Koblenz, Rheinland-Pfalz, Germany, 56068
      • GSK Investigational Site
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • GSK Investigational Site
    • Rhaunen, Rheinland-Pfalz, Germany, 55624
      • GSK Investigational Site
  • Sachsen
    • Leipzig, Sachsen, Germany, 04275
      • GSK Investigational Site
  • Thueringen
    • Erfurt, Thueringen, Germany, 99084
      • GSK Investigational Site
• Japan
  • Fukuoka, Japan, 802-0052
    • GSK Investigational Site
  • Fukuoka, Japan, 832-0059
    • GSK Investigational Site
  • Hokkaido, Japan, 064-0801
    • GSK Investigational Site
  • Kagoshima, Japan, 892-0844
    • GSK Investigational Site
  • Kagoshima, Japan, 890-0064
    • GSK Investigational Site
  • Kanagawa, Japan, 252-0143
    • GSK Investigational Site
  • Kyoto, Japan, 612-0026
    • GSK Investigational Site
  • Kyoto, Japan, 601-8206
    • GSK Investigational Site
  • Saitama, Japan, 343-0808
    • GSK Investigational Site
  • Tokyo, Japan, 153-0051
    • GSK Investigational Site
  • Tokyo, Japan, 187-0024
    • GSK Investigational Site
  • Tokyo, Japan, 113-0031
    • GSK Investigational Site
  • Tokyo, Japan, 190-0013
    • GSK Investigational Site
  • Tokyo, Japan, 204-0021
    • GSK Investigational Site
• Mexico
  • Mexico City, Mexico, 07760
    • GSK Investigational Site
  • Mexico city, Mexico, 04530
    • GSK Investigational Site
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44100
      • GSK Investigational Site
    • Zapopan, Jalisco, Mexico, 45040
      • GSK Investigational Site
  • Nuevo León
    • Monterrey NL, Nuevo León, Mexico, 64718
      • GSK Investigational Site
  • Tabasco
    • Villahermosa, Tabasco, Mexico, 86100
      • GSK Investigational Site
• Philippines
  • Iloilo City, Philippines, 5000
    • GSK Investigational Site
  • Lipa City, Philippines, 4217
    • GSK Investigational Site
  • Marilao, Bulacan, Philippines, 3019
    • GSK Investigational Site
  • Quezon City, Philippines, 1101
    • GSK Investigational Site
  • Quezon City, Philippines, 1109
    • GSK Investigational Site
• Poland
  • Bydgoszcz, Poland, 85-681
    • GSK Investigational Site
  • Debica, Poland, 39-200
    • GSK Investigational Site
  • Gdansk, Poland, 80-169
    • GSK Investigational Site
  • Kielce, Poland
    • GSK Investigational Site
  • Koszalin, Poland
    • GSK Investigational Site
  • Krakow, Poland, 31-159
    • GSK Investigational Site
  • Lublin, Poland, 20-954
    • GSK Investigational Site
  • Lublin, Poland, 20-089
    • GSK Investigational Site
  • Olsztyn, Poland, 10-357
    • GSK Investigational Site
  • Poznan, Poland, 60-214
    • GSK Investigational Site
  • Poznan, Poland, 60-693
    • GSK Investigational Site
  • Rzeszow, Poland
    • GSK Investigational Site
  • Wolomin, Poland, 05-200
    • GSK Investigational Site
  • Wroclaw, Poland, 54-239
    • GSK Investigational Site
  • Wroclaw, Poland, 50-445
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 050159
    • GSK Investigational Site
  • Bucharest, Romania, 020674
    • GSK Investigational Site
  • Craiova, Romania, 200341
    • GSK Investigational Site
  • Deva, Romania, 330084
    • GSK Investigational Site
  • Pitesti, Romania, 110084
    • GSK Investigational Site
  • Sibiu, Romania, 550166
    • GSK Investigational Site
• Russian Federation
  • Barnaul, Russian Federation, 656 045
    • GSK Investigational Site
  • Blagoveshchensk, Russian Federation, 675000
    • GSK Investigational Site
  • Chelyabinsk, Russian Federation, 454106
    • GSK Investigational Site
  • Kazan, Russian Federation, 420015
    • GSK Investigational Site
  • Krasnodar, Russian Federation
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630087
    • GSK Investigational Site
  • Novosibirsk, Russian Federation, 630047
    • GSK Investigational Site
  • Penza, Russian Federation, 440067
    • GSK Investigational Site
  • Perm, Russian Federation, 614077
    • GSK Investigational Site
  • Pyatigorsk, Russian Federation, 357538
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 194354
    • GSK Investigational Site
  • Saratov, Russian Federation, 410028
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 197022
    • GSK Investigational Site
  • Tomsk, Russian Federation, 634001
    • GSK Investigational Site
  • Volgodonsk, Russian Federation, 347381
    • GSK Investigational Site
  • Voronezh, Russian Federation, 394018
    • GSK Investigational Site
• Ukraine
  • Dnipropetrovsk, Ukraine, 49051
    • GSK Investigational Site
  • Donetsk, Ukraine, 83017
    • GSK Investigational Site
  • Kyiv, Ukraine, 02091
    • GSK Investigational Site
  • Kyiv, Ukraine, 03680
    • GSK Investigational Site
  • Kyiv, Ukraine, 03038
    • GSK Investigational Site
  • Kyiv, Ukraine, 03115
    • GSK Investigational Site
  • Kyiv, Ukraine, 02660
    • GSK Investigational Site
  • Kyiv, Ukraine, 04050
    • GSK Investigational Site
  • Kyiv, Ukraine, 04201
    • GSK Investigational Site
  • Simferopol, Ukraine, 95034
    • GSK Investigational Site
  • Vinnytsia, Ukraine, 21029
    • GSK Investigational Site
  • Yalta, Ukraine, 98603
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69063
    • GSK Investigational Site
  • Zaporizhia, Ukraine, 69076
    • GSK Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • GSK Investigational Site
    • Mobile, Alabama, United States, 36608
      • GSK Investigational Site
    • Oxford, Alabama, United States, 36203
      • GSK Investigational Site
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • GSK Investigational Site
    • Scottsdale, Arizona, United States, 85251
      • GSK Investigational Site
    • Tucson, Arizona, United States, 85724-5073
      • GSK Investigational Site
  • California
    • Bell Gardens, California, United States, 90201
      • GSK Investigational Site
    • Fresno, California, United States, 93721
      • GSK Investigational Site
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Long Beach, California, United States, 90808
      • GSK Investigational Site
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
    • Mission Viejo, California, United States, 92691
      • GSK Investigational Site
    • Napa, California, United States, 94558
      • GSK Investigational Site
    • Rancho Mirage, California, United States, 92270
      • GSK Investigational Site
    • Riverside, California, United States, 92506
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
    • Roseville, California, United States, 95661
      • GSK Investigational Site
    • San Diego, California, United States, 92120
      • GSK Investigational Site
    • Stockton, California, United States, 95207
      • GSK Investigational Site
    • Torrance, California, United States, 90505
      • GSK Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80230
      • GSK Investigational Site
    • Englewood, Colorado, United States, 80112
      • GSK Investigational Site
  • Florida
    • Cocoa, Florida, United States, 32927
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Valrico, Florida, United States, 33596
      • GSK Investigational Site
    • Winter Park, Florida, United States, 32789
      • GSK Investigational Site
  • Georgia
    • Albany, Georgia, United States, 31707
      • GSK Investigational Site
    • Columbus, Georgia, United States, 31904
      • GSK Investigational Site
    • Lawrenceville, Georgia, United States, 30046
      • GSK Investigational Site
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • GSK Investigational Site
  • Illinois
    • River Forest, Illinois, United States, 60305
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46256
      • GSK Investigational Site
  • Kentucky
    • Hazard, Kentucky, United States, 41701
      • GSK Investigational Site
    • Owensboro, Kentucky, United States, 42301
      • GSK Investigational Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • GSK Investigational Site
    • Sunset, Louisiana, United States, 70584
      • GSK Investigational Site
  • Maryland
    • Baltimore, Maryland, United States, 21236
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10461
      • GSK Investigational Site
    • Rockville Center, New York, United States, 11570
      • GSK Investigational Site
  • Ohio
    • Canton, Ohio, United States, 44718
      • GSK Investigational Site
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
    • Sylvania, Ohio, United States, 43560
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • GSK Investigational Site
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • Oregon
    • Eugene, Oregon, United States, 97401
      • GSK Investigational Site
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • Pennsylvania
    • Collegeville, Pennsylvania, United States, 19426
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19107
      • GSK Investigational Site
    • Philadelphia, Pennsylvania, United States, 19115
      • GSK Investigational Site
    • Pittsburgh, Pennsylvania, United States, 15241
      • GSK Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • GSK Investigational Site
    • Gaffney, South Carolina, United States, 29340
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
    • Union, South Carolina, United States, 29379
      • GSK Investigational Site
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78750
      • GSK Investigational Site
    • Houston, Texas, United States, 77074
      • GSK Investigational Site
    • Houston, Texas, United States, 77054
      • GSK Investigational Site
    • Killeen, Texas, United States, 76542
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • GSK Investigational Site
    • Waco, Texas, United States, 76712
      • GSK Investigational Site
  • Vermont
    • South Burlington, Vermont, United States, 05403
      • GSK Investigational Site
  • Washington
    • Bellingham, Washington, United States, 98225
      • GSK Investigational Site
  • Wisconsin
    • La Crosse, Wisconsin, United States, 54601
      • 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:

• Clinical diagnosis of asthma
• Reversibility FEV1 of twelve percent or greater and two hundred milliliters and greater approximately ten to forty minutes following two to four inhalations of albuterol
• FEV1 of fifty to ninety percent of predicted
• Currently using inhaled corticosteroid therapy
• History of one or more asthma exacerbations requiring treatment with oral/systemic corticosteroids or emergency department visit or in-patient hospitalization in previous year

Exclusion Criteria:

• History of life threatening asthma in previous 5 years (requiring intubation, and/or associated with hypercapnia, hypoxic seizure or respiratory arrest
• Respiratory infection or oral candidiasis
• - Uncontrolled disease or clinical abnormality
• Allergies
• Taking another investigational medication or prohibited medication

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone furoate/GW642444	Drug: Fluticasone Furoate/GW642444; Combination inhaled corticosteroid and long-acting beta2-agonist
Experimental: fluticasone furoate	Drug: Fluticasone furoate; Inhaled corticosteroid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 1 or More Severe Asthma Exacerbations	Asthma is a medical condition that causes narrowing of the small airways in the lungs. A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Only events deemed by the adjudication committee to be severe asthma exacerbations were used in the analysis of severe asthma exacerbations. The time to the first severe asthma exacerbation was analyzed using a Cox proportional hazards regression model, adjusting for Baseline disease severity (Baseline forced expiratory volume in one second [FEV1, maximum amount of air forcefully exhaled in one second]), sex, age, and region.	Baseline to Follow-up (up to 76 weeks of treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Severe Asthma Exacerbations	A severe asthma exacerbation is defined as a deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. A participant may have had one or more exacerbations.	Baseline to Follow-up (up to 76 weeks of treatment)
Change From Baseline in Evening Pre-dose Trough FEV1 at Week 36	Evening pre-dose trough (lowest value) forced expiratory volume in one second (FEV1) was measured using spirometry equipment that met or exceeded the minimal performance recommendations of the American Thoracic Society. FEV1 is a measure of the maximum amount of air forcefully exhaled in one second. Change from Baseline in evening pre-dose FEV1 was analyzed using an Analysis of Covariance (ANCOVA) model with effects due to Baseline FEV1, sex, age, region, and treatment. Change from Baseline was calculated as the Week 36 value minus the Baseline value.	Baseline and Week 36

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.
• Gross AS, Goldfrad C, Hozawa S, James MH, Clifton CS, Sugiyama Y, Jacques L. Ethnic sensitivity assessment of fluticasone furoate/vilanterol in East Asian asthma patients from randomized double-blind multicentre Phase IIb/III trials. BMC Pulm Med. 2015 Dec 24;15:165. doi: 10.1186/s12890-015-0159-z.
• Bateman ED, O'Byrne PM, Busse WW, Lotvall J, Bleecker ER, Andersen L, Jacques L, Frith L, Lim J, Woodcock A. Once-daily fluticasone furoate (FF)/vilanterol reduces risk of severe exacerbations in asthma versus FF alone. Thorax. 2014 Apr;69(4):312-9. doi: 10.1136/thoraxjnl-2013-203600. Epub 2013 Nov 19.

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: February 22, 2010
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): September 15, 2011

Study Registration Dates

• First Submitted: March 11, 2010
• First Submitted That Met QC Criteria: March 11, 2010
• First Posted (Estimate): March 15, 2010

Study Record Updates

• Last Update Posted (Actual): January 24, 2018
• Last Update Submitted That Met QC Criteria: January 18, 2018
• Last Verified: January 1, 2018

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: 106837

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: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Clinical Study Report
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Individual Participant Data Set
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Study Protocol
   Information identifier: 106837
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register