HZA113091 Efficacy and Safety of Fluticasone Furoate/Vilanterol (GW642444) in Adults and Adolescents

A Randomised, Double-blind, Double-dummy, Parallel-group Multicentre Study to Assess Efficacy and Safety of Fluticasone Furoate/GW642444 Inhalation Powder and Fluticasone Propionate/Salmeterol Inhalation Powder 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 with fluticasone propionate/salmeterol administered twice daily 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; Drug: Placebo (2); Drug: Fluticasone propionate/salmeterol Inhalation Powder; Drug: Placebo (1)

• Study Type: Interventional
• Enrollment (Actual): 810
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424BSF
    • GSK Investigational Site
  • Buenos Aires, Argentina, 1425
    • GSK Investigational Site
  • Buenos Aires, Argentina, C1425BEN
    • GSK Investigational Site
  • Ciudad Autónoma de Buenos Aires, Argentina, C1426ABP
    • GSK Investigational Site
  • Mendoza, Argentina, M5500CCG
    • GSK Investigational Site
  • San Miguel de Tucumán, 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
    • Rosario, Santa Fe, Argentina, S2000JKR
      • GSK Investigational Site
• Chile
  • Reg Del Libert Bern Ohiggins
    • Rancagua, Reg Del Libert Bern Ohiggins, Chile, 2841959
      • GSK Investigational Site
  • Región Metro De Santiago
    • Puente Alto - Santiago, Región Metro De Santiago, Chile, 8207257
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7500691
      • GSK Investigational Site
    • Santiago, Región Metro De Santiago, Chile, 7601003
      • GSK Investigational Site
  • Valparaíso
    • Valparaiso, Valparaíso, Chile, 2341131
      • GSK Investigational Site
    • Viña del Mar, Valparaíso, Chile
      • GSK Investigational Site
• Korea, Republic of
  • Cheongju, Chungcheongbuk-do, Korea, Republic of, 361-711
    • GSK Investigational Site
  • Incheon, Korea, Republic of, 400-711
    • GSK Investigational Site
  • Kangwon-do, Korea, Republic of, 220-701
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 138-736
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 110-744
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 135-710
    • GSK Investigational Site
  • Suwon, Kyonggi-do, Korea, Republic of, 443-721
    • GSK Investigational Site
• Netherlands
  • Almelo, Netherlands, 7609 PP
    • GSK Investigational Site
  • Breda, Netherlands, 4819 EV
    • GSK Investigational Site
  • Dordrecht, Netherlands, 3318 AT
    • GSK Investigational Site
  • Eindhoven, Netherlands, 5623 EJ
    • GSK Investigational Site
  • Harderwijk, Netherlands, 3844 DG
    • GSK Investigational Site
  • Heerlen, Netherlands, 6419 PC
    • GSK Investigational Site
  • Hoorn, Netherlands, 1624 NP
    • GSK Investigational Site
  • Veldhoven, Netherlands, 5504 DB
    • GSK Investigational Site
• Philippines
  • Cabanatuan City, Nueva Ecija, Philippines, 3100
    • GSK Investigational Site
  • Cebu City, Philippines, 6000
    • GSK Investigational Site
  • Dasmariñas, Cavite, Philippines, 4114
    • GSK Investigational Site
  • Manila, Philippines, 1000
    • GSK Investigational Site
  • Marilao, Bulacan, Philippines, 3019
    • GSK Investigational Site
  • Quezon City, Philippines, 1100
    • GSK Investigational Site
• United States
  • California
    • Huntington Beach, California, United States, 92647
      • GSK Investigational Site
    • Los Angeles, California, United States, 90025
      • GSK Investigational Site
    • Los Angeles, California, United States, 90048
      • GSK Investigational Site
    • Riverside, California, United States, 92506
      • GSK Investigational Site
    • Rolling Hills Estates, California, United States, 90274
      • GSK Investigational Site
    • San Diego, California, United States, 92117
      • GSK Investigational Site
  • Colorado
    • Centennial, Colorado, United States, 80112
      • GSK Investigational Site
    • Denver, Colorado, United States, 80230
      • GSK Investigational Site
  • Florida
    • Cocoa, Florida, United States, 32927
      • GSK Investigational Site
  • Maryland
    • Bethesda, Maryland, United States, 20814
      • GSK Investigational Site
    • Wheaton, Maryland, United States, 20902
      • GSK Investigational Site
  • Missouri
    • Rolla, Missouri, United States, 65401
      • GSK Investigational Site
    • St. Louis, Missouri, United States, 63141
      • GSK Investigational Site
  • New Jersey
    • Cherry Hill, New Jersey, United States, 08003
      • GSK Investigational Site
    • Skillman, New Jersey, United States, 08558
      • GSK Investigational Site
  • North Carolina
    • Raleigh, North Carolina, United States, 27607
      • GSK Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45231
      • GSK Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • GSK Investigational Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • GSK Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29615
      • GSK Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • GSK Investigational Site
    • Spartanburg, South Carolina, United States, 29303
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78750
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78229
      • 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:

• Clinical diagnosis of asthma
• Reversibility of at least 12% and at least 200mLs within 10-40 minutes following 2-4 inhalations of albuterol
• FEV1 of 40-85% predicted normal
• Currently using inhaled corticosteroid therapy

Exclusion Criteria:

• History of life-threatening asthma within previous 5 years (requiring intubation and/or was associated with hypercapnoea, respiratory arrest or hypoxic seizures)
• Respiratory infection or oral candidiasis
• Asthma exacerbation requiring oral corticosteroids or that resulted in overnight hospitalisation requiring additional asthma treatment
• Uncontrolled disease or clinical abnormality
• Allergies
• Taking another investigational medication or prohibited medication
• Night shift workers
• Current smokers or subjects with smoking history of at least 10 pack years

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Fluticasone furoate/Vilanterol (GW642444); 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; Drug: Placebo (2); Inhalation powder inhaled orally twice daily for 24 weeks
Active Comparator: Fluticasone propionate/salmeterol; Fluticasone propionate/salmeterol inhalation powder twice daily + placebo inhalation powder once daily for 24 weeks	Drug: Fluticasone propionate/salmeterol Inhalation Powder; Fluticasone propionate/salmeterol Inhalation Powder inhaled orally twice daily for 24 weeks; Drug: Placebo (1); Inhalation powder inhaled orally once daily for 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Weighted-mean 24 Hour Serial FEV1 on Day 168/Week 24	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5, 15, and 30 minutes (min) and at 1, 2, 3, 4, 11, 12, 12.5, 13, 14, 16, 20, 23, and 24 hours, respectively, on Day 168/Week 24. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 168/Week 24 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline FEV1, region, sex, age, and treatment.	Baseline and Day 168/Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serial FEV1 (0-24 Hours)	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second . The pre-dose FEV1 assessment and the individual serial FEV1 assessments at Day 168/Week 24 at the indicated time points (pre-dose, 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, 4 hours, 11 hours, 12 hours, 12.5 hours, 13 hours, 14 hours, 16 hours, 20 hours, 23 hours, and 24 hour s) were summarized.	Day 168
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1	Time to onset of bronchodilator effect at Day 1 is defined as the actual time during the 4-hour serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) measurements that the participant first meets or exceeds a 12% and 200 mL increase over Baseline and was derived at Day 1 only. Time to onset was calculated over 0 to 4 hours (5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 3 hours, and 4 hours) post-dose. Participants who never exceeded a 12% and 200 mL increase over Baseline were censored at the actual time of their last FEV1 measurement.	Baseline to Day 1
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours Post First Dose (at Randomization)	The weighted mean serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) over 0-4 hours post-dose at Baseline was derived using actual times and using the pre-dose assessment as the 0 hour measurement. Change from Baseline was calculated as the weighted mean of the 4-hour serial FEV1 measures on Day 1 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using ANCOVA with covariates of Baseline FEV1, region, sex, age, and treatment.	Baseline and Randomization
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours at Day 168	The weighted mean serial FEV1 (the maximal amount of air that can be forcefully exhaled in one second) over 0-4 hours post-dose at Baseline and Day 168 was derived using actual times and using the pre-dose assessment as the 0 hour measurement. Change from Baseline was calculated as the weighted mean of the 4-hour serial FEV1 measures on Day 168/Week 24 minus the Baseline value. Baseline was the pre-dose measurement on Day 1. Analysis was performed using ANCOVA with covariates of Baseline FEV1, region, sex, age, and treatment.	Baseline and Day 168
Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1	The number of participants obtaining a >=12% and >=200 mL increase from Baseline in FEV1 (the maximal amount of air that can be forcefully exhaled in one second) was evaluated at 12-hours post-dose and at 24-hours post-dose on Day 168.	Baseline and Day 168
Change From Baseline in Trough FEV1 at Day 168	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second . Trough FEV1 is defined as the pre-dose measurement on Day 168/Week 24. Any missing data at Day 168/Week 24 was imputed using the last observation carried forward (LOCF). Baseline was the pre-dose measurement on Day 1. Change from Baseline was calculated as the pre-dose measurement on Day 168/Week 24 minus the Baseline value.	Baseline and Day 168

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline FEV1 by Completion Status	Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second . Baseline is defined as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.	Baseline
Change From Baseline in Asthma Control Test (ACT) Scores at Day 168	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 Day 168 value minus the Baseline value.	Baseline and Day 168
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168	All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (to the general ward [GW] or the intensive care unit [ICU]) that were associated with asthma exacerbations were recorded.	Baseline to Day 168
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score for Participants 12 Years of Age and Older (AQLQ + 12)	The AQLQ is a disease-specific, self-administered quality of life (QOL) questionnaire developed to evaluate the impact of asthma treatments on the QOL of asthma sufferers. The AQLQ contains 32 items in four domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). The response format consists of a 7-point scale: a value of 1 indicates "total impairment"; a value of 7 indicates "no impairment." The AQLQ total score is defined as the average of the scores from all 32 questions, provided at least 90% of the questions have been answered; thus, the total score ranges from 1 (indicates "total impairment") to 7 (indicates "no impairment"). Change from Baseline was calculated as the Day 168 value minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline total AQLQ score, country, sex, age, and treatment.	Baseline and Day 168
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24	The EQ-5D is a standardized, 2-part, self-assessment instrument, designed for self-completion, used to measure health outcome. The first part consists of 5 items covering 5 dimensions (mobility, self care, usual activities, pain/discomfort, and anxiety/depression). Each dimension is measured by a three-point Likert scale (1=no problems, 2=some problems and 3=severe problems). Respondents are asked to choose one level that reflects their "own health state today" for each of the five dimensions.	Day 168/Week 24
Change From Baseline in EQ-5D Visual Analog Scale (VAS) Score at Day 168	The EQ-5D is a standardized, 2-part, self-assessment instrument, designed for self-completion, used to measure health outcome. The first part consists of 5 items covering 5 dimensions (mobility, self care, usual activities, pain/discomfort, and anxiety/depression). The second part is a 20 centimeter VAS that has endpoints labelled "best imaginable health state" and "worst imaginable health state" anchored at 100 and 0, respectively. Participants were asked to indicate how they rate their own health by drawing a line from an anchor box to that point on the EQ-VAS that best represents their own health on that day. Analysis was performed using ANCOVA with covariates of Baseline VAS score, country, sex, age, and treatment.	Baseline and Day 168

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Woodcock A, Bleecker ER, Lotvall J, O'Byrne PM, Bateman ED, Medley H, Ellsworth A, Jacques L, Busse WW. Efficacy and safety of fluticasone furoate/vilanterol compared with fluticasone propionate/salmeterol combination in adult and adolescent patients with persistent asthma: a randomized trial. Chest. 2013 Oct;144(4):1222-1229. doi: 10.1378/chest.13-0178.

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): July 1, 2011
• Study Completion (Actual): July 1, 2011

Study Registration Dates

• First Submitted: May 27, 2010
• First Submitted That Met QC Criteria: June 17, 2010
• First Posted (Estimate): June 22, 2010

Study Record Updates

• Last Update Posted (Estimate): January 18, 2017
• Last Update Submitted That Met QC Criteria: November 30, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: GW642444; fluticasone propionate; Salmeterol; fluticasone furoate; Vilanterol
• 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; Anti-Allergic Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Fluticasone; Xhance; Salmeterol Xinafoate
• Other Study ID Numbers: 113091

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: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Annotated Case Report Form
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Informed Consent Form
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Statistical Analysis Plan
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Individual Participant Data Set
   Information identifier: 113091
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register