Trial Outcomes & Findings for HZA113091 Efficacy and Safety of Fluticasone Furoate/Vilanterol (GW642444) in Adults and Adolescents (NCT NCT01147848)

NCT ID: NCT01147848

Last Updated: 2017-01-18

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 810 participants
• Primary outcome timeframe: Baseline and Day 168/Week 24
• Results posted on: 2017-01-18

Participant Flow

Participant milestones

Measure	Fluticasone Propionate 250 µg BID Participants received Fluticasone Propionate 250 micrograms (µg) twice a day (BID) and salbutamol/albuterol as required to control symptoms.	Fluticasone Furoate/Vilanterol 100/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Run-in Period STARTED	1564	0	0
Run-in Period COMPLETED	806	0	0
Run-in Period NOT COMPLETED	758	0	0
Randomized Phase STARTED	0	403	403
Randomized Phase COMPLETED	0	358	357
Randomized Phase NOT COMPLETED	0	45	46

Reasons for withdrawal

Measure	Fluticasone Propionate 250 µg BID Participants received Fluticasone Propionate 250 micrograms (µg) twice a day (BID) and salbutamol/albuterol as required to control symptoms.	Fluticasone Furoate/Vilanterol 100/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Run-in Period Screen Failure	623	0	0
Run-in Period Run-in Failure	135	0	0
Randomized Phase Adverse Event	0	6	8
Randomized Phase Lack of Efficacy	0	20	11
Randomized Phase Protocol Violation	0	7	10
Randomized Phase Lost to Follow-up	0	5	7
Randomized Phase Physician Decision	0	0	1
Randomized Phase Withdrawal by Subject	0	7	9

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=403 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=403 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.	Total n=806 Participants Total of all reporting groups
Age, Continuous	43.8 Years STANDARD_DEVIATION 15.86 • n=5 Participants	41.9 Years STANDARD_DEVIATION 16.90 • n=7 Participants	42.8 Years STANDARD_DEVIATION 16.41 • n=5 Participants
Gender Female	244 Participants n=5 Participants	245 Participants n=7 Participants	489 Participants n=5 Participants
Gender Male	159 Participants n=5 Participants	158 Participants n=7 Participants	317 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	36 participants n=5 Participants	43 participants n=7 Participants	79 participants n=5 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	40 participants n=5 Participants	46 participants n=7 Participants	86 participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	81 participants n=5 Participants	79 participants n=7 Participants	160 participants n=5 Participants
Race/Ethnicity, Customized Asian - Mixed Race	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	241 participants n=5 Participants	232 participants n=7 Participants	473 participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	0 participants n=5 Participants	2 participants n=7 Participants	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 168/Week 24

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least 1 dose of double-blind medication. Randomized participants were assumed to have received double-blind medication unless definitive evidence to the contrary existed. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=352 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=347 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Weighted-mean 24 Hour Serial FEV1 on Day 168/Week 24	0.341 Liters Standard Error 0.0184	0.377 Liters Standard Error 0.0185

SECONDARY outcome

Timeframe: Day 168

Population: ITT Population. Only those participants available at the indicated time points were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=359 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=354 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Serial FEV1 (0-24 Hours) 14 hours, n=356, 353	0.357 Liters Standard Deviation 0.3643	0.426 Liters Standard Deviation 0.4201
Serial FEV1 (0-24 Hours) Pre-dose, n=359,353	0.304 Liters Standard Deviation 0.3575	0.323 Liters Standard Deviation 0.4289
Serial FEV1 (0-24 Hours) 5 minutes, n=356, 344	0.320 Liters Standard Deviation 0.3573	0.339 Liters Standard Deviation 0.4146
Serial FEV1 (0-24 Hours) 15 minutes, n=355, 347	0.323 Liters Standard Deviation 0.3565	0.354 Liters Standard Deviation 0.4054
Serial FEV1 (0-24 Hours) 30 minutes, n=357, 351	0.339 Liters Standard Deviation 0.3614	0.366 Liters Standard Deviation 0.4184
Serial FEV1 (0-24 Hours) 1 hour, n=358, 353	0.344 Liters Standard Deviation 0.3760	0.390 Liters Standard Deviation 0.4227
Serial FEV1 (0-24 Hours) 2 hours, n=359, 353	0.362 Liters Standard Deviation 0.3749	0.409 Liters Standard Deviation 0.4204
Serial FEV1 (0-24 Hours) 3 hours, n=357, 353	0.373 Liters Standard Deviation 0.3764	0.419 Liters Standard Deviation 0.4173
Serial FEV1 (0-24 Hours) 4 hours, n=357, 354	0.356 Liters Standard Deviation 0.3695	0.417 Liters Standard Deviation 0.4254
Serial FEV1 (0-24 Hours) 11 hours, n=359, 347	0.305 Liters Standard Deviation 0.3761	0.319 Liters Standard Deviation 0.4099
Serial FEV1 (0-24 Hours) 12 hours, n=356, 354	0.330 Liters Standard Deviation 0.3691	0.338 Liters Standard Deviation 0.4142
Serial FEV1 (0-24 Hours) 12.5 hours, n=357, 352	0.330 Liters Standard Deviation 0.3682	0.380 Liters Standard Deviation 0.4117
Serial FEV1 (0-24 Hours) 13 hours, n=354, 354	0.343 Liters Standard Deviation 0.3602	0.396 Liters Standard Deviation 0.4139
Serial FEV1 (0-24 Hours) 16 hours, n=354, 350	0.351 Liters Standard Deviation 0.3672	0.419 Liters Standard Deviation 0.4152
Serial FEV1 (0-24 Hours) 20 hours, n=355, 352	0.321 Liters Standard Deviation 0.3757	0.376 Liters Standard Deviation 0.4150
Serial FEV1 (0-24 Hours) 23 hours, n=354, 353	0.310 Liters Standard Deviation 0.3814	0.344 Liters Standard Deviation 0.4141
Serial FEV1 (0-24 Hours) 24 hours, n=354, 354	0.304 Liters Standard Deviation 0.3725	0.340 Liters Standard Deviation 0.4032

SECONDARY outcome

Timeframe: Baseline to Day 1

Population: ITT Population. Only those participants available at the indicated time points were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=400 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=401 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 30 minutes	40 participants	55 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 5 minutes	100 participants	85 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 15 minutes	41 participants	51 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 1 hour	32 participants	39 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 2 hours	19 participants	29 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 3 hours	17 participants	12 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 4 hours	11 participants	12 participants
Number of Participants With the Indicated Time to Onset of Bronchodilator Effect at Day 1 Censored	140 participants	118 participants

SECONDARY outcome

Timeframe: Baseline and Randomization

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=398 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=398 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours Post First Dose (at Randomization)	0.316 Liters Standard Error 0.0149	0.346 Liters Standard Error 0.0149

SECONDARY outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=356 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=347 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Weighted Mean Serial FEV1 Over 0-4 Hours at Day 168	0.360 Liters Standard Deviation 0.0184	0.394 Liters Standard Deviation 0.0186

SECONDARY outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time points were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=356 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=354 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1 12 hours post-dose, n=356,354	199 participants	178 participants
Number of Participants Obtaining a >=12% and >=200 mL Increase From Baseline in FEV1 24 hours post-dose, n=354, 354	181 participants	176 participants

SECONDARY outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=397 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=389 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Trough FEV1 at Day 168	0.281 Liters Standard Error 0.0191	0.300 Liters Standard Error 0.0193

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=401 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=401 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Baseline FEV1 by Completion Status All Participants, n=401, 401	2.011 Liters Standard Deviation 0.6389	2.048 Liters Standard Deviation 0.6246
Baseline FEV1 by Completion Status Completers, n=359, 355	2.013 Liters Standard Deviation 0.6530	2.043 Liters Standard Deviation 0.6378
Baseline FEV1 by Completion Status Withdrawals, n=42, 46	1.996 Liters Standard Deviation 0.5081	2.091 Liters Standard Deviation 0.5145

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed. Analysis was performed using ANCOVA with covariates of Baseline total ACT score, country, sex, age, and treatment.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=354 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=348 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Asthma Control Test (ACT) Scores at Day 168	2.3 Scores on a scale Standard Error 0.16	2.0 Scores on a scale Standard Error 0.16

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=403 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=403 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Inpatient Hospitalization (ICU) Days	0.0 visits per participant Standard Deviation 0.00	0.0 visits per participant Standard Deviation 0.0
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Home Visits during the Day	0.0 visits per participant Standard Deviation 0.0	0.0 visits per participant Standard Deviation 0.05
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Home Visits during the Night	0.0 visits per participant Standard Deviation 0.0	0.0 visits per participant Standard Deviation 0.0
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Physician Office/Practice Visits	0.0 visits per participant Standard Deviation 0.29	0.0 visits per participant Standard Deviation 0.18
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Urgent Care/Outpatient Clinic Visits	0.0 visits per participant Standard Deviation 0.05	0.0 visits per participant Standard Deviation 0.05
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Emergency Room Visits	0.0 visits per participant Standard Deviation 0.15	0.0 visits per participant Standard Deviation 0.14
Number of Healthcare Contacts Related to Asthma or the Treatment of Asthma From Baseline to Day 168 Number of Inpatient Hospitalization (GW) Days	0.0 visits per participant Standard Deviation 0.20	0.0 visits per participant Standard Deviation 0.39

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=342 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=335 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Total Score for Participants 12 Years of Age and Older (AQLQ + 12)	0.46 Scores on a scale Standard Error 0.043	0.37 Scores on a scale Standard Error 0.043

OTHER_PRE_SPECIFIED outcome

Timeframe: Day 168/Week 24

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=403 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=403 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 Mobility	86 percentage of participants	84 percentage of participants
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 Self care	98 percentage of participants	98 percentage of participants
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 Usual activities	86 percentage of participants	82 percentage of participants
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 Pain/Discomfort	70 percentage of participants	66 percentage of participants
Percentage of Participants With "No Problems" in the EQ-5D Descriptive System Dimensions at Day 168/Week 24 Anxiety/Depression	78 percentage of participants	81 percentage of participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

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.

Outcome measures

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=343 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=349 Participants Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Change From Baseline in EQ-5D Visual Analog Scale (VAS) Score at Day 168	5.5 scores on a scale Standard Error 0.60	4.1 scores on a scale Standard Error 0.60

Adverse Events

Fluticasone Furoate/Vilanterol 100/25 µg OD

Serious events: 4 serious events

Other events: 110 other events

Deaths: 0 deaths

Fluticasone Propionate/Salmeterol 250/50 µg BID

Serious events: 5 serious events

Other events: 106 other events

Deaths: 0 deaths

Serious adverse events

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=403 participants at risk Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=403 participants at risk Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Infections and infestations Pneumonia	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Infections and infestations Upper respiratory tract infection	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Infections and infestations Urinary tract infection	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Respiratory, thoracic and mediastinal disorders Asthma	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.50% 2/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Cardiac disorders Myocardial ischaemia	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Hepatobiliary disorders Cholelithiasis	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Injury, poisoning and procedural complications Carbon monoxide poisoning	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Psychiatric disorders Disorientation	0.00% 0/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	0.25% 1/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.

Other adverse events

Measure	Fluticasone Furoate/Vilanterol 100/25 µg OD n=403 participants at risk Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 µg once daily (OD) in the evening, plus placebo inhalation powder twice daily (BID; in the morning and evening) for a period of 24 weeks.	Fluticasone Propionate/Salmeterol 250/50 µg BID n=403 participants at risk Participants received Fluticasone Propionate (FP)/Salmeterol 250/50 µg inhalation powder BID (in the morning and evening), plus placebo inhalation powder OD in the evening for a period of 24 weeks.
Infections and infestations Nasopharyngitis	11.4% 46/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	11.4% 46/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Infections and infestations Upper respiratory tract infection	6.2% 25/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	4.0% 16/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Nervous system disorders Headache	8.4% 34/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	10.2% 41/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
Respiratory, thoracic and mediastinal disorders Cough	3.7% 15/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	3.2% 13/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
General disorders Pyrexia	3.2% 13/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.	1.2% 5/403 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of the study medication until Follow-up (up to 544 days). All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.

Additional Information

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Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER