FFA112059

GlaxoSmithKline

980 Great West Road, Brentford, Middlesex, United Kingdom,

GSK Response Center, GlaxoSmithKline, 1 8664357343,

GSK Response Center, GlaxoSmithKline, 1 8664357343,

Yes

No

Yes

Final

15 Feb 2012

No

Yes

16 Jan 2012

No

To evaluate the efficacy and safety of fluticasone furoate 100mcg administered once daily in the evening in adolescent and adult subjects 12 years of age and older with persistent bronchial asthma over a 24 week treatment period.

The following withdrawal criteria for lack of efficacy were included: A participant who met any of the following efficacy criteria was to have been withdrawn from the study: 1. Clinic FEV1 below the FEV1 stability limit value calculated at Visit 2 2. During the 7 days immediately preceding any visit, the participant experienced: a) At least 4 days in which the PEF fell below the PEF Stability Limit calculated at Visit 2; OR b) At least 3 days in which >=12 inhalations/day of albuterol/salbutamol were used. 3. Participants who experience a protocol-defined severe exacerbation, defined as deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. 4. Clinical asthma worsening that in the opinion of the investigator requires additional asthma treatment other than study medication or study-supplied albuterol/salbutamol.

30 Jun 2010

No

No

Poland: 94

Romania: 74

Belgium: 106

Germany: 67

United States: 695

1036

341

0

0

0

0

0

121

857

58

0

Overall Study (overall period)

Randomised - controlled

Yes

Placebo

Inhalation powder

Inhalation use

Matching placebo

Fluticasone furoate

Inhalation powder

Inhalation use

100 micrograms (µg) once daily

Fluticasone propionate

Inhalation powder

Inhalation use

250 µg twice daily

Placebo

FF 100 µg OD

FP 250 µg BID

Placebo

FF 100 µg OD

FP 250 µg BID

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 at the end of the dosing interval. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline through Week 24 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 2. Change from Baseline was calculated as the Week 24 value minus the Baseline value. Analysis was performed using analysis of covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment. The last observation carried forward (LOCF) method was used to impute missing data, in which the last non-missing post-Baseline on-treatment measurement at scheduled clinic visits was used to impute the missing measurements.

Primary

Baseline and Week 24

Placebo v FF 100 µg OD

224

Pre-specified

0.146

2-sided

Placebo v FP 250 µg BID

220

Pre-specified

0.145

2-sided

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 was considered to be rescue 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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Week 24

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 evening PEF is the PM PEF measured approximately 24 hours after the last evening 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 PM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Secondary

From Baseline up to Week 12 and Week 24

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. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over 12 weeks and 24 weeks of the 24-week Treatment Period (at Weeks 12 and 24) minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Secondary

From Baseline up to Week 12 and Week 24

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 symptoms was considered to be 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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Week 24

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 ages 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.

Secondary

Baseline, Week 12, and Week 24

Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication to the end of the treatment period (up to Week 24).

An on-therapy AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of study medication.

14.1

Placebo

FF 100 µg OD

FP 250 µg BID