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

Asthma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01147848
• Other study ID #: 113091
• Status: Completed
• Phase: Phase 3
• First received: May 27, 2010
• Last updated: July 10, 2014
• Start date: June 2010
• Est. completion date: July 2011

Study information

• Verified date: September 2013
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Ministry of Health - A.N.M.A.TChile: Instituto de Salud Pública de ChileNetherlands: Ministry of Health, Welfare and SportsPhilippines: Bureau of Food and DrugsSouth Korea: Food and Drug AdministrationUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 810
• Est. completion date: July 2011
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 12 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

Drug:
• Fluticasone furoate/Vilanterol Inhalation Powder
Fluticasone furoate/Vilanterol Inhalation Powder inhaled orally once daily for 24 weeks
• Fluticasone propionate/salmeterol Inhalation Powder
Fluticasone propionate/salmeterol Inhalation Powder inhaled orally twice daily for 24 weeks
• Placebo (1)
Inhalation powder inhaled orally once daily for 24 weeks
• Placebo (2)
Inhalation powder inhaled orally twice daily for 24 weeks

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autónoma de Buenos Aires
Argentina	GSK Investigational Site	Mendoza
Argentina	GSK Investigational Site	Parana	Entre Ríos
Argentina	GSK Investigational Site	Quilmes	Buenos Aires
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	Rosario	Santa Fe
Argentina	GSK Investigational Site	San Miguel de Tucumán
Chile	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Rancagua	Reg Del Libert Bern Ohiggins
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Santiago	Región Metro De Santiago
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Chile	GSK Investigational Site	Viña del Mar	Valparaíso
Korea, Republic of	GSK Investigational Site	Cheongju, Chungcheongbuk-do
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Kangwon-do
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Suwon, Kyonggi-do
Netherlands	GSK Investigational Site	Almelo
Netherlands	GSK Investigational Site	Breda
Netherlands	GSK Investigational Site	Dordrecht
Netherlands	GSK Investigational Site	Eindhoven
Netherlands	GSK Investigational Site	Harderwijk
Netherlands	GSK Investigational Site	Heerlen
Netherlands	GSK Investigational Site	Hoorn
Netherlands	GSK Investigational Site	Veldhoven
Philippines	GSK Investigational Site	Cabanatuan City, Nueva Ecija
Philippines	GSK Investigational Site	Cebu City
Philippines	GSK Investigational Site	Dasmariñas, Cavite
Philippines	GSK Investigational Site	Manila
Philippines	GSK Investigational Site	Marilao, Bulacan
Philippines	GSK Investigational Site	Quezon City
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bethesda	Maryland
United States	GSK Investigational Site	Centennial	Colorado
United States	GSK Investigational Site	Cherry Hill	New Jersey
United States	GSK Investigational Site	Cincinnati	Ohio
United States	GSK Investigational Site	Cocoa	Florida
United States	GSK Investigational Site	Denver	Colorado
United States	GSK Investigational Site	Greenville	South Carolina
United States	GSK Investigational Site	Huntington Beach	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Medford	Oregon
United States	GSK Investigational Site	Oklahoma City	Oklahoma
United States	GSK Investigational Site	Orangeburg	South Carolina
United States	GSK Investigational Site	Raleigh	North Carolina
United States	GSK Investigational Site	Riverside	California
United States	GSK Investigational Site	Rolla	Missouri
United States	GSK Investigational Site	Rolling Hills Estates	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	Skillman	New Jersey
United States	GSK Investigational Site	Spartanburg	South Carolina
United States	GSK Investigational Site	St. Louis	Missouri
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	Wheaton	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Chile,  Korea, Republic of,  Netherlands,  Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Other	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No