Study HZA106829: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics

HZA106829: A Randomised, Double-blind, Parallel Group, Multicentre Study of Fluticasone Furoate/GW642444 Inhalation Powder, Fluticasone Furoate Inhalation Powder Alone, and Fluticasone Propionate Alone in the Treatment of Persistent Asthma in Adults and Adolescents

The purpose of the study is to compare the efficacy and safety of fluticasone furoate/vilanterol (GW642444) inhalation powder administered once daily each evening with fluticasone furoate inhalation powder administered alone once daily each evening in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24-week period.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Fluticasone Furoate/Vilanterol Inhalation Powder; Other: Placebo Inhalation Powder 2; Drug: Fluticasone Furoate Inhalation Powder; Drug: Fluticasone Propionate Inhalation Powder; Other: Placebo Inhalation Powder 1

• Study Type: Interventional
• Enrollment (Actual): 587
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Hamburg, Germany, 20354
    • GSK Investigational Site
  • Brandenburg
    • Cottbus, Brandenburg, Germany, 03050
      • GSK Investigational Site
    • Schwedt, Brandenburg, Germany, 16303
      • GSK Investigational Site
  • Hessen
    • Frankfurt, Hessen, Germany, 60389
      • GSK Investigational Site
    • Gelnhausen, Hessen, Germany, 63571
      • GSK Investigational Site
    • Kassel, Hessen, Germany, 34121
      • GSK Investigational Site
    • Ruesselsheim, Hessen, Germany, 65428
      • GSK Investigational Site
  • Niedersachsen
    • Hannover, Niedersachsen, Germany, 30167
      • GSK Investigational Site
  • Schleswig-Holstein
    • Geesthacht, Schleswig-Holstein, Germany, 21502
      • GSK Investigational Site
    • Luebeck, Schleswig-Holstein, Germany, 23552
      • GSK Investigational Site
• Japan
  • Fukuoka, Japan, 811-1394
    • GSK Investigational Site
  • Hiroshima, Japan, 732-0052
    • GSK Investigational Site
  • Hyogo, Japan, 672-8048
    • GSK Investigational Site
  • Ishikawa, Japan, 920-8530
    • GSK Investigational Site
  • Kagawa, Japan, 762-0031
    • GSK Investigational Site
  • Kyoto, Japan, 603-8161
    • GSK Investigational Site
  • Okayama, Japan, 712-8064
    • GSK Investigational Site
  • Okinawa, Japan, 901-2132
    • GSK Investigational Site
  • Shizuoka, Japan, 430-8558
    • GSK Investigational Site
  • Shizuoka, Japan, 438-8550
    • GSK Investigational Site
  • Tokyo, Japan, 158-0083
    • GSK Investigational Site
  • Tokyo, Japan, 105-0003
    • GSK Investigational Site
• Poland
  • Bialystok, Poland, 15-010
    • GSK Investigational Site
  • Dzialdowo, Poland, 13-200
    • GSK Investigational Site
  • Gdansk, Poland, 84-462
    • GSK Investigational Site
  • Gdansk, Poland, 80-169
    • GSK Investigational Site
  • Gliwice, Poland, 44-100
    • GSK Investigational Site
  • Krakow, Poland, 31-202
    • GSK Investigational Site
  • Piekary Slaskie, Poland, 41-940
    • GSK Investigational Site
  • Sopot, Poland, 81-741
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 020125
    • GSK Investigational Site
  • Bucharest, Romania, 030317
    • GSK Investigational Site
  • Iasi, Romania, 700115
    • GSK Investigational Site
  • Oradea, Romania, 410176
    • GSK Investigational Site
  • Ploiesti, Romania, 100550
    • GSK Investigational Site
  • Suceava, Romania, 720284
    • GSK Investigational Site
  • Timisoara, Romania, 300310
    • GSK Investigational Site
• Russian Federation
  • Ekaterinburg, Russian Federation, 620109
    • GSK Investigational Site
  • Kazan, Russian Federation, 420015
    • GSK Investigational Site
  • Moscow, Russian Federation, 123182
    • GSK Investigational Site
  • Moscow, Russian Federation, 115446
    • GSK Investigational Site
  • Moscow, Russian Federation, 127018
    • GSK Investigational Site
  • Moscow, Russian Federation, 125367
    • GSK Investigational Site
  • Moscow, Russian Federation, 115 280
    • GSK Investigational Site
  • Ryazan,, Russian Federation, 390026
    • GSK Investigational Site
  • Smolensk, Russian Federation, 214001
    • GSK Investigational Site
  • St. Petersburg, Russian Federation, 198216
    • GSK Investigational Site
  • Yaroslavl, Russian Federation
    • GSK Investigational Site
• United States
  • California
    • Bell Gardens, California, United States, 90201
      • 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
    • Riverside, California, United States, 92506
      • GSK Investigational Site
    • Roseville, California, United States, 95661
      • GSK Investigational Site
    • San Diego, California, United States, 92128
      • GSK Investigational Site
  • Florida
    • Clearwater, Florida, United States, 33756
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Panama City, Florida, United States, 32405
      • GSK Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • GSK Investigational Site
  • Illinois
    • Normal, Illinois, United States, 61761
      • GSK Investigational Site
    • River Forest, Illinois, United States, 60305
      • GSK Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
    • Oklahoma City, Oklahoma, United States, 73112
      • GSK Investigational Site
  • Oregon
    • Lake Oswego, Oregon, United States, 97035
      • GSK Investigational Site
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78756
      • GSK Investigational Site
    • El Paso, Texas, United States, 79925
      • GSK Investigational Site
    • Sugar Land, Texas, United States, 77479
      • 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:

• Outpatient at least 12 years of age
• Both genders; females of childbearing potential must be willing to use birth control method
• Pre-bronchodilator FEV1 of 40-90% predicted
• Reversibility FEV1 of at least 12% and 200mls
• Current asthma therapy that includes an inhaled corticosteroid for at least 12 weeks prior to first visit

Exclusion Criteria:

• History of life-threatening asthma
• Respiratory infection or oral candidiasis
• Asthma exacerbation within 12 weeks
• Concurrent respiratory disease or other disease that would confound study participation or affect subject safety
• Allergies to study drugs, study drugs' excipients, medications related to study drugs
• Taking another investigational medication or medication prohibited for use during this study

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone Furoate/Vilanterol; Fluticasone furoate/vilanterol inhalation powder once daily + Placebo inhalation powder twice daily for 24 weeks	Drug: Fluticasone Furoate/Vilanterol Inhalation Powder; Fluticasone furoate/Vilanterol inhalation powder inhaled orally once daily for 24 weeks; Other: Placebo Inhalation Powder 2; Placebo in Diskus inhaler twice daily
Active Comparator: Fluticasone Furoate; Fluticasone furoate inhalation powder once daily + Placebo inhalation powder twice daily for 24 weeks	Other: Placebo Inhalation Powder 2; Placebo in Diskus inhaler twice daily; Drug: Fluticasone Furoate Inhalation Powder; Fluticasone furoate inhalation powder inhaled orally once daily for 24 weeks
Active Comparator: Fluticasone Propionate; Fluticasone propionate inhalation powder twice daily + Placebo inhalation powder once daily for 24 weeks	Drug: Fluticasone Propionate Inhalation Powder; Fluticasone propionate inhalation powder inhaled orally twice daily for 24 weeks; Other: Placebo Inhalation Powder 1; Placebo in novel dry powder inhaler once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Clinic Visit Trough (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. Trough FEV1 is defined as the clinic visit (pre-bronchodilator and pre-dose) FEV1 measurement taken at the clinic visit while still on treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline (BL) through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. BL was the pre-dose value obtained at Visit 3. Change from BL was calculated as the Week 24 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of BL trough FEV1, country, sex, age, and treatment group.The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-BL on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.	Baseline and Week 24
Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 24 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and the post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.	Baseline and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the Percentage of Rescue-free and Symptom-free 24-hour Periods at the End of 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). Similarly, 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 use of rescue medication/symptoms was considered to be rescue free/symptom free. The Baseline value was derived from 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.	Baseline and Week 24
Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12 and Week 24/Early Withdrawal	The AQLQ is a disease-specific, self-administered quality of life questionnaire used to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ for 12 years and older (AQLQ [+12]) is a modified version of the AQLQ for use in asthma patients between the age of 12 and 70. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). For the 32 items on the questionnaire, the response format consists of a seven-point scale, where a value of 1 indicates "total impairment" and a value of 7 indicates "no impairment." The AQLQ total score is defined as the average of the scores from all 32 questions; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Baseline was the total score obtained at Visit 3. Change from Baseline was calculated as the total score at Weeks 12 and 24 minus the total score at Baseline.	Baseline, Week 12, and Week 24/Early Withdrawal

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinic Visit 12-hour Post-dose FEV1at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. 12-hour post-dose FEV1 measurements were taken electronically by spirometry at the Week 24 clinic visit. The highest of 3 technically acceptable measurements was recorded.	Week 24
Change From Baseline in Weighted Mean Serial FEV1 Over 0 to 4 Hours Post-dose at Week 24	FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Baseline. Weighted mean was calculated using the 4-hour serial FEV1 measurements that included the pre-dose assessment (within 5 minutes prior to dosing) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, and 4 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 24 FEV1 value minus the Baseline value.	Baseline and Week 24
Mean Change From Baseline in Daily Morning Trough (AM) and Evening (PM) Peak Expiratory Flow (PEF) Averaged Over the First 12 Weeks and 24 Weeks of 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. Trough PEF is the PEF measured approximately 24 hours after the last administration of study drug. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily trough AM/PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value.	From Baseline up to Week 12 and Week 24
The Number of Participants Who Withdrew Due to Lack of Efficacy During the 24-week Treatment Period	The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.	From the first dose of the study medication up to Week 24/Early Withdrawal
Change From Baseline in the Asthma Control Test (ACT) Scores at Week 12 and Week 24	The ACT is a 5-item questionnaire developed as a measure of the participant's asthma control. Questions are designed to be self-completed by the participant and include the following: In the past 4 weeks, "How much of the time did your asthma keep you from getting as much done at work, school or at home?", "How often have you had shortness of breath?", "How often did your asthma symptoms wake you up at night or earlier than usual in the morning?", "How often have you used your rescue inhaler or nebulizer medication (such as albuterol)?" and "How would you rate your asthma control"? The ACT total score is defined as the sum of the scores from all 5 questions, provided all questions have been answered; thus, the total score ranges from 5 (poor control of asthma) to 25 (complete control of asthma). A score of 20 or higher indicates well-controlled asthma. Change from Baseline was calculated as the total score at Week 12 and Week 24/Early Withdrawal minus the total score at Baseline.	Baseline, Week 12, and Week 24/Early Withdrawal
Number of Participants With the Indicated Global Assessment of Change Questionnaire Responses at Weeks 4, 12, and 24	At the end of Week 4, Week 8, and Week 24/Early Withdrawal, the Global Assessment of Change Questionnaire that assesses changes in asthma symptoms (AS) and rescue medication use (RMU) was completed by the participants. The number of participants who chose the following answers to the questionnaire were determined: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse (to assess the changes in asthma symptoms); much less often, somewhat less often, a little less often, the same, a little more often, somewhat more often, much more often (to assess the changes in the frequency of rescue medication use).	Week 4, Week 12, and Week 24/Early Withdrawal
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period	All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (ICU=intensive care unit; GW=general ward) associated with severe asthma exacerbations or other asthma-related healthcare issues were recorded.	From Baseline up to Week 24/Withdrawal Visit

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.
• Kosinski M, Nelsen L, Rizio AA, Lay-Flurrie J, von Maltzahn R, Jacques L, Schatz M, Stanford RH, Svedsater H. Psychometric properties of the Asthma Control Test in 2 randomized clinical trials. J Allergy Clin Immunol Pract. 2021 Jan;9(1):561-563.e1. doi: 10.1016/j.jaip.2020.07.040. Epub 2020 Aug 6. No abstract available.
• O'Byrne PM, Bleecker ER, Bateman ED, Busse WW, Woodcock A, Forth R, Toler WT, Jacques L, Lotvall J. Once-daily fluticasone furoate alone or combined with vilanterol in persistent asthma. Eur Respir J. 2014 Mar;43(3):773-82. doi: 10.1183/09031936.00064513. Epub 2013 Oct 17.

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: June 1, 2010
• Primary Completion (Actual): October 1, 2011
• Study Completion (Actual): October 1, 2011

Study Registration Dates

• First Submitted: May 27, 2010
• First Submitted That Met QC Criteria: May 27, 2010
• First Posted (Estimate): May 31, 2010

Study Record Updates

• Last Update Posted (Estimate): January 11, 2017
• Last Update Submitted That Met QC Criteria: November 23, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: asthma; Fluticasone propionate; GW642444; vilanterol; 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; 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: 106829

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. Dataset Specification
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Clinical Study Report
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 106829
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register