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

Phase 3

Completed

Conditions: Asthma

Interventions: Drug: Fluticasone furoate/Vilanterol Inhalation Powder
Drug: Fluticasone propionate/salmeterol Inhalation Powder
Drug: Placebo (1)
Drug: Placebo (2)

Registration Number: NCT01147848

Lead Sponsor: GlaxoSmithKline

Brief 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 810

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

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fluticasone furoate/Vilanterol (GW642444)	Fluticasone furoate/Vilanterol Inhalation Powder	Fluticasone furoate/vilanterol inhalation powder once daily + placebo inhalation powder twice daily for 24 weeks
Fluticasone propionate/salmeterol	Placebo (1)	Fluticasone propionate/salmeterol inhalation powder twice daily + placebo inhalation powder once daily for 24 weeks
Fluticasone furoate/Vilanterol (GW642444)	Placebo (2)	Fluticasone furoate/vilanterol inhalation powder once daily + placebo inhalation powder twice daily for 24 weeks
Fluticasone propionate/salmeterol	Fluticasone propionate/salmeterol Inhalation Powder	Fluticasone propionate/salmeterol inhalation powder twice daily + placebo inhalation powder once daily for 24 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Weighted-mean 24 Hour Serial FEV1 on Day 168/Week 24	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1	Baseline to 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.
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours at Day 168	Baseline and 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.
Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1	Baseline and Day 168	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.
Serial FEV1 (0-24 Hours)	Day 168	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.
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours Post First Dose (at Randomization)	Baseline and 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.
Change From Baseline in Trough FEV1 at Day 168	Baseline and 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.