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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01147848
First received: May 27, 2010
Last updated: July 10, 2014
Last verified: September 2013
  Purpose

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.


Condition Intervention Phase
Asthma
Drug: Fluticasone furoate/Vilanterol Inhalation Powder
Drug: Fluticasone propionate/salmeterol Inhalation Powder
Drug: Placebo (1)
Drug: Placebo (2)
Phase 3

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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in Weighted-mean 24 Hour Serial FEV1 on Day 168/Week 24 [ Time Frame: Baseline and Day 168/Week 24 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Serial FEV1 (0-24 Hours) [ Time Frame: Day 168 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 [ Time Frame: Baseline to Day 1 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours Post First Dose (at Randomization) [ Time Frame: Baseline and Randomization ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours at Day 168 [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.

  • Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1 [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Trough FEV1 at Day 168 [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Baseline FEV1 by Completion Status [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Asthma Control Test (ACT) Scores at Day 168 [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.

  • Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 [ Time Frame: Baseline to Day 168 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score for Participants 12 Years of Age and Older (AQLQ + 12) [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 [ Time Frame: Day 168/Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in EQ-5D Visual Analog Scale (VAS) Score at Day 168 [ Time Frame: Baseline and Day 168 ] [ Designated as safety issue: No ]
    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.


Enrollment: 810
Study Start Date: June 2010
Study Completion Date: July 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   12 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01147848

  Show 63 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01147848     History of Changes
Other Study ID Numbers: 113091
Study First Received: May 27, 2010
Results First Received: June 6, 2013
Last Updated: July 10, 2014
Health Authority: Argentina: Ministry of Health - A.N.M.A.T
Chile: Instituto de Salud Pública de Chile
Netherlands: Ministry of Health, Welfare and Sports
Philippines: Bureau of Food and Drugs
South Korea: Food and Drug Administration
United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Salmeterol
fluticasone furoate
Vilanterol
fluticasone propionate
GW642444

Additional relevant MeSH terms:
Asthma
Bronchial Diseases
Hypersensitivity
Hypersensitivity, Immediate
Immune System Diseases
Lung Diseases
Lung Diseases, Obstructive
Respiratory Hypersensitivity
Respiratory Tract Diseases
Fluticasone
Salmeterol
Adrenergic Agents
Adrenergic Agonists
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Anti-Allergic Agents
Anti-Asthmatic Agents
Anti-Inflammatory Agents
Autonomic Agents
Bronchodilator Agents
Dermatologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014