HZA116863

GlaxoSmithKline

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

GSK Response Center, GlaxoSmithKline, +1 8664357343,

GSK Response Center, GlaxoSmithKline, +1 8664357343,

No

No

No

Final

03 Dec 2013

No

Yes

15 Oct 2013

No

To compare the efficacy and safety of once daily (evening) administration of FF/VI 100/25 with FF 100 in adult and adolescent subjects ≥ 12 years of age with moderate to severe, persistent bronchial asthma over 12 weeks.

Upon initial entry into the trial, participants were assessed for their fitness for the study by a physical examination, chemistry/hematology laboratory tests, serum pregnancy (females of child-bearing potential), and electrocardiogram (ECG) results. Medical, asthma, and previous asthma treatment histories were obtained along with pulmonary function testing. Reversibility was also established. Stability limits of 80% of the participant’s pre-albuterol FEV1 and peak expiratory flow rate were determined at the randomization visit to assist the investigators in monitoring participant’ asthma status throughout the study. Twice each day (morning and evening), participants rated their asthma symptoms and measured their PEF. Participants were instructed to contact the investigator if the PEF fell below the established limit. Albuterol inhalation was provided for rescue use, and use was monitored each morning and evening when the other assessments were performed. Pulmonary function was assessed at each visit via spirometry. Vital signs were also taken at each visit, and the participants were questioned in regard to their health and non-serious adverse events/serious adverse events that may have occurred since their last visit. Two medics supported the study and were available for consultation with the investigators as needed.

20 Sep 2012

No

No

Netherlands: 62

Poland: 84

Sweden: 50

Germany: 129

Argentina: 241

Chile: 146

Mexico: 51

Romania: 192

Russian Federation: 295

Ukraine: 165

United States: 604

2019

517

0

0

0

0

0

120

1646

252

1

Overall Study (overall period)

Randomised - controlled

Yes

Fluticasone furoate

Inhalation powder

Respiratory use

100 µg once daily

Fluticasone furoate/vilanterol

Inhalation powder

Respiratory use

100 µg/25 µg once daily

Fluticasone furoate/vilanterol

Inhalation powder

Respiratory use

200 micrograms (µg)/25 µg once daily

FF 100 µg OD

FF/VI 100/25 µg OD

FF/VI 200/25 µg OD

FF 100 µg OD

FF/VI 100/25 µg OD

FF/VI 200/25 µg OD

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 (within 30 minutes prior to dosing) and post-dose FEV1 measurements at 5, 15, and 30 minutes and at 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours on Day 84/Week 12. At each time point, the highest of three technically acceptable measurements was recorded. Change from Baseline was calculated as the weighted mean of the 24-hour serial FEV1 measures on Day 84/Week 12 minus the Baseline value. Baseline was the pre-dose FEV1 measurement value obtained at Visit 3. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline FEV1, region, sex, age, and treatment. Intent-to-Treat (ITT) Population: all participants randomized to treatment, who recevied at least one dose of the study medication

Primary

Baseline and Week 12

FF 100 µg OD v FF/VI 100/25 µg OD

600

Pre-specified

0.108

2-sided

FF/VI 100/25 µg OD v FF/VI 200/25 µg OD

624

Pre-specified

0.024

2-sided

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 a pre-dose FEV1 measurement taken at a clinic visit while still on-treatment. Change from Baseline in trough FEV1 at the end of the 12-week treatment period was defined using the 24-hour post-dose serial FEV1 measurement taken at the Week 12 clinic visit. Change from Baseline was calculated as the Week 12 trough FEV1 value minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline trough FEV1, 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.

Secondary

Baseline and Week 12

The number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants in a daily electronic diary (eDiary). A 24-hour (hr) 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Weeks 1-12

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 (hr) 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 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Weeks 1-12

Peak Expiratory Flow (PEF) 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 evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use and each morning. The best of three measurements was recorded. 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 the 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Weeks 1-12

PEF 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 evening prior to the dose of study medication and any rescue albuterol/salbutamol inhalation aerosol use and each morning. The best of three measurements was recorded. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 12-week treatment period minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment.

Secondary

Baseline and Weeks 1-12

Serious Adverse Events (SAEs) and non-serious AEs were collected from the first dose of study medication up to Week 12/Early Withdrawal.

SAEs and AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of the study medication.

16.1

FF 100 µg OD

FF/VI 100/25 µg OD

FF/VI 200/25 µg OD