Trial Outcomes & Findings for Study HZA106827: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics (NCT NCT01165138)

Last Updated: 2018-02-14

Results Overview

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 clinic visit (pre-bronchodilator and pre-dose) FEV1measurement taken at the clinic visit while still on-treatment. Pre-dose and pre-rescue albuterol/salbutamol trough FEV1 was measured electronically by spirometry in the evening at the Baseline through Week 12 clinic visits. The highest of 3 technically acceptable measurements was recorded. Baseline was the pre-dose value obtained at Visit 3. Change from Baseline was calculated as the Week 12 value minus the Baseline value. The analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline trough FEV1, region, sex, age, and treatment group. 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 m

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

612 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2018-02-14

Participant Flow

Participants meeting eligibility criteria at the Screening visit completed a 4-week Run-in Period for Baseline safety evaluations and measures of asthma status. Participants were then randomized to a 12-week Treatment Period. 1110 participants were screened, 610 were randomized, and 609 received \>=1 dose of study treatment.

Participant milestones

Participant milestones
Measure	Placebo Participants (par.) received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Overall Study STARTED	203	205	201
Overall Study COMPLETED	151	185	179
Overall Study NOT COMPLETED	52	20	22

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants (par.) received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Overall Study Adverse Event	1	0	2
Overall Study Lack of Efficacy	32	6	7
Overall Study Protocol Violation	7	0	2
Overall Study Lost to Follow-up	0	1	2
Overall Study Physician Decision	6	7	6
Overall Study Withdrawal by Subject	6	6	3

Baseline Characteristics

Study HZA106827: Efficacy/Safety Study of Fluticasone Furoate/Vilanterol (GW642444) in Adult and Adolescent Asthmatics

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=203 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	Total n=609 Participants Total of all reporting groups
Age, Continuous	38.1 Years STANDARD_DEVIATION 16.49 • n=5 Participants	40.4 Years STANDARD_DEVIATION 16.78 • n=7 Participants	40.7 Years STANDARD_DEVIATION 16.38 • n=5 Participants	39.7 Years STANDARD_DEVIATION 16.56 • n=4 Participants
Sex: Female, Male Female	111 Participants n=5 Participants	126 Participants n=7 Participants	116 Participants n=5 Participants	353 Participants n=4 Participants
Sex: Female, Male Male	92 Participants n=5 Participants	79 Participants n=7 Participants	85 Participants n=5 Participants	256 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	14 participants n=5 Participants	16 participants n=7 Participants	13 participants n=5 Participants	43 participants n=4 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	19 participants n=5 Participants	16 participants n=7 Participants	15 participants n=5 Participants	50 participants n=4 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	169 participants n=5 Participants	170 participants n=7 Participants	172 participants n=5 Participants	511 participants n=4 Participants
Race/Ethnicity, Customized Mixed Race	1 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	2 participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment, who received at least one dose of the study medication. Only those participants with non-missing covariates and post-Baseline FEV1 data were analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=193 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=203 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=200 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Mean Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) Forced Expiratory Volume in One Second (FEV1) at Week 12	0.196 Liters Standard Error 0.0310	0.332 Liters Standard Error 0.0302	0.368 Liters Standard Error 0.0304

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population. Weighted mean serial FEV1 was calculated for the subset of participants for whom serial FEV1 was performed at Week 12.

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 12 clinic visits. Weighted mean was calculated using the 24-hour serial FEV1 measurements that included the pre-dose assessment (within 30 minutes prior to dosing at Baseline and within 5 minutes prior to dosing at Week 12) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, 4, 5, 12, 16, 20, 23, and 24 hours. At each time point, the highest of 3 technically acceptable measurements was recorded. Baseline was the value obtained at Visit 3. Change from Baseline was calculated as the average Week 12 FEV1 value minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline FEV1, region, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=95 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=106 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=108 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Week 12	0.212 Liters Standard Error 0.0456	0.398 Liters Standard Error 0.0432	0.513 Liters Standard Error 0.0430

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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 group.

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=204 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Mean Change From Baseline in the Percentage of Rescue-free 24-hour (hr) Periods During the 12-week Treatment Period	17.8 Percentage of rescue-free 24-hr periods Standard Error 2.26	26.5 Percentage of rescue-free 24-hr periods Standard Error 2.25	37.1 Percentage of rescue-free 24-hr periods Standard Error 2.26

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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 group.

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=204 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in the Percentage of Symptom-free 24-hour (hr) Periods During the 12-week Treatment Period	14.6 Percentage of symptom-free 24-hr periods Standard Error 2.15	20.4 Percentage of symptom-free 24-hr periods Standard Error 2.13	32.5 Percentage of symptom-free 24-hr periods Standard Error 2.14

SECONDARY outcome

Timeframe: Baseline and Week 12/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.

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 age 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 Week 12 minus the total score at Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=149 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=184 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=180 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in the Total Asthma Quality of Life Questionnaire (AQLQ) (+12) Score at Week 12/Early Withdrawal	0.61 Score on a scale Standard Error 0.061	0.76 Score on a scale Standard Error 0.055	0.91 Score on a scale Standard Error 0.055

SECONDARY outcome

Timeframe: From the first dose of the study medication up to Week 12/Early Withdrawal

Population: ITT Population

The number of participants whose primary reason for withdrawal was lack of efficacy was analyzed.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants Who Withdrew Due to Lack of Efficacy During the 12-week Treatment Period	32 participants	6 participants	7 participants

SECONDARY outcome

Timeframe: Randomization

Population: ITT Population. Serial FEV1 was calculated for the subset of participants for whom serial FEV1 was performed. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at Randomization. Serial FEV1 measurements after 5, 15, and 30 minutes and 1 hour post-dose were assessed. At each time point, the highest of 3 technically acceptable measurements was recorded. The analysis was performed using a repeated measures model adjusted for baseline, region, sex, age, treatment group, and planned time points.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Serial FEV1 Over 0-1 Hour Post-dose at Randomization 1 Hour, n=119, 116, 119	2.552 Liters Standard Error 0.0344	2.571 Liters Standard Error 0.0350	2.674 Liters Standard Error 0.0344
Serial FEV1 Over 0-1 Hour Post-dose at Randomization 5 Minutes, n=117, 112, 117	2.489 Liters Standard Error 0.0308	2.493 Liters Standard Error 0.0314	2.484 Liters Standard Error 0.0308
Serial FEV1 Over 0-1 Hour Post-dose at Randomization 15 Minutes, n=118, 115, 117	2.491 Liters Standard Error 0.0336	2.529 Liters Standard Error 0.0342	2.566 Liters Standard Error 0.0336
Serial FEV1 Over 0-1 Hour Post-dose at Randomization 30 Minutes, n=118, 116, 118	2.532 Liters Standard Error 0.0354	2.552 Liters Standard Error 0.0359	2.596 Liters Standard Error 0.0354

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 12

Population: ITT Population. 12-hour post-dose FEV1 was analyzed in the subset of participants for whom serial FEV1 at Week 12 was performed.

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. 12-hour post-dose FEV1 measurements were taken electronically by spirometry at the Week 12 clinic visit. The highest of 3 technically acceptable measurements was recorded. The analysis was performed using an ANCOVA model with covariates of Baseline FEV1, region, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=93 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=104 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=108 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Clinic Visit 12-hour Post-dose FEV1 at Week 12	2.462 Liters Standard Error 0.0502	2.674 Liters Standard Error 0.0475	2.830 Liters Standard Error 0.0468

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: ITT Population. Weighted mean serial FEV1 was calculated in the subset of participants for whom serial FEV1 was performed.

Outcome measures

Outcome measures
Measure	Placebo n=119 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=116 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=119 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Weighted Mean Serial FEV1 Over 0-24 Hours Post-dose at Baseline	2.543 Liters Standard Deviation 0.8494	2.552 Liters Standard Deviation 0.7527	2.709 Liters Standard Deviation 0.8153

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 12

Population: ITT Population. Weighted mean serial FEV1 was calculated in the subset of participants for whom serial FEV1 at Week 12 was performed. Only those participants available at the specified time points were analyzed.

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry at the Baseline and Week 12 clinic visits. Weighted mean serial FEV1 over 0-4 hours was calculated using the serial FEV1 measurements that included the pre-dose assessment (within 30 minutes prior to dosing at Baseline and within 5 minutes prior to dosing at Week 12) and post-dose assessments after 5, 15, and 30 minutes and 1, 2, 3, and 4 hours. At each time point, the highest of 3 technically acceptable measurements were recorded. Baseline was the value obtained at Visit 3.

Outcome measures

Outcome measures
Measure	Placebo n=120 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=115 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=119 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Weighted Mean Serial FEV1 Over 0-4 Hours Post-dose at Baseline and Week 12 Baseline, n=120, 115, 119	2.563 Liters Standard Deviation 0.8194	2.522 Liters Standard Deviation 0.7479	2.693 Liters Standard Deviation 0.7626
Weighted Mean Serial FEV1 Over 0-4 Hours Post-dose at Baseline and Week 12 Week 12, n=96, 105, 109	2.636 Liters Standard Deviation 0.8519	2.657 Liters Standard Deviation 0.7912	2.894 Liters Standard Deviation 0.8383

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline

Population: ITT Population. Only the subset of participants performing serial measurements were analyzed.

Bronchodilator effect is defined as an increase of FEV1 (defined as the maximal amount of air that can be forcefully exhaled in one second) from Baseline of both 12% and 200 milliliters (mL) during 24 hours, which was evaluated using the serial FEV1 measurements at Baseline (Visit 3).

Outcome measures

Outcome measures
Measure	Placebo n=120 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=116 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=120 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With Bronchodilator Effect	73 participants Interval 0.0 to 272.0	77 participants Interval 0.0 to 270.0	97 participants Interval 0.0 to 62.0

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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

Outcome measures

Outcome measures
Measure	Placebo n=103 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=204 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Mean Change From Baseline in Daily Morning (AM) Peak Expiratory Flow (PEF) Averaged Over the 12-week Treatment Period	-0.4 Liters per minute Standard Error 2.42	18.3 Liters per minute Standard Error 2.41	32.9 Liters per minute Standard Error 2.42

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 12

Population: ITT Population. Only those participants available at the specified time points were analyzed.

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. 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 (at Week 12) minus the Baseline value. The analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age, and treatment group.

Outcome measures

Outcome measures
Measure	Placebo n=202 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=204 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Mean Change From Baseline in Daily Evening (PM) PEF Averaged Over the 12-week Treatment Period	-1.8 Liters per minute Standard Error 2.36	14.1 Liters per minute Standard Error 2.34	26.4 Liters per minute Standard Error 2.35

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 12/Early Withdrawal

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 total score at Week 12/Early Withdrawal minus the total score at Baseline.

Outcome measures

Outcome measures
Measure	Placebo n=154 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=189 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=185 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in the Asthma Control Test (ACT) Score at Week 12	2.5 Scores on a scale Standard Error 0.26	3.8 Scores on a scale Standard Error 0.23	4.4 Scores on a scale Standard Error 0.23

OTHER_PRE_SPECIFIED outcome

Timeframe: Week 4, Week 8, and Week 12/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed.

At the end of Week 4, Week 8, and Week 12/Early Withdrawal, the Global Assessment of Change Questionnaire that assesses changes in asthma symptoms (AS) and rescue medication use (RMU) was completed by the participants. The number of participants who chose the following answers to the questionnaire were determined: much better, somewhat better, a little better, the same, a little worse, somewhat worse, much worse (to assess the changes in asthma symptom); much less often , somewhat less often , a little less often , the same , a little more often , somewhat more often , much more often (to assess the changes in the frequency of rescue medication use).

Outcome measures

Outcome measures
Measure	Placebo n=174 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=198 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=191 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - A little better, n=174, 198, 191	42 participants	47 participants	37 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - The same, n=174, 198, 191	33 participants	29 participants	23 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - A little worse, n=174, 198, 191	6 participants	10 participants	3 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - Much worse, n=174, 198, 191	6 participants	0 participants	0 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - Much less often, n=174, 198, 191	39 participants	59 participants	75 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - A little more often, n=174, 198, 191	13 participants	6 participants	4 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - Much better, n=174, 198, 191	34 participants	47 participants	65 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - Somewhat better, n=174, 198, 191	45 participants	65 participants	61 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, AS - Somewhat worse, n=174, 198, 191	8 participants	0 participants	2 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - Somewhat less often, n=174, 198, 191	40 participants	48 participants	51 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - A little less often, n=174, 198, 191	35 participants	49 participants	32 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - The same, n=174, 198, 191	31 participants	33 participants	28 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - Somewhat more often, n=174, 198, 191	11 participants	3 participants	1 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 4, RMU - Much more often, n=174, 198, 191	5 participants	0 participants	0 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - Much better, n=159, 192, 184	36 participants	54 participants	69 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - Somewhat better, n=159, 192, 184	44 participants	60 participants	63 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - A little better, n=159, 192, 184	38 participants	40 participants	22 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - The same, n=159, 192, 184	29 participants	33 participants	24 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - A little worse, n=159, 192, 184	7 participants	5 participants	3 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - Somewhat worse, n=159, 192, 184	4 participants	0 participants	2 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, AS - Much worse, n=159, 192, 184	1 participants	0 participants	1 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - Much less often, n=159, 191, 184	37 participants	65 participants	86 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - Somewhat less often, n=159, 191, 184	32 participants	48 participants	43 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - A little less often, n=159, 191, 184	37 participants	34 participants	25 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - The same, n=159, 191, 184	36 participants	39 participants	23 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - A little more often, n=159, 191, 184	12 participants	1 participants	5 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - Somewhat more often, n=159, 191, 184	4 participants	4 participants	0 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 8, RMU - Much more often, n=159, 191, 184	1 participants	0 participants	2 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - Much better, n=152, 187, 182	38 participants	66 participants	86 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - Somewhat better, n=152, 187, 182	37 participants	49 participants	52 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - A little better, n=152, 187, 182	29 participants	35 participants	13 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - The same, n=152, 187, 182	29 participants	30 participants	23 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - A little worse, n=152, 187, 182	9 participants	7 participants	7 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - Somewhat worse, n=152, 187, 182	6 participants	0 participants	1 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, AS - Much worse, n=152, 187, 182	4 participants	0 participants	0 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU - Much less often, n=150, 187, 182	42 participants	76 participants	89 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU -Somewhat less often, n=150, 187, 182	32 participants	46 participants	43 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU -A little less often, n=150, 187, 182	24 participants	25 participants	21 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU - The same, n=150, 187, 182	34 participants	32 participants	23 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU -A little more often, n=150, 187, 182	12 participants	6 participants	5 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU -Somewhat more often, n=150, 187, 182	3 participants	1 participants	1 participants
Number of Participants With the Indicated Global Assessment of Change Responses at Week 4, Week 8, and Week 12/Early Withdrawal Week 12, RMU - Much more often, n=150, 187, 182	3 participants	1 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: From Baseline up to Week 12/Early Withdrawal

Population: ITT Population

All unscheduled asthma-related visits to a physician's office, visits to urgent care, visits to the emergency department, and hospitalizations (ICU=intensive care unit; GW=general ward) associated with severe asthma exacerbations or other asthma-related healthcare were recorded.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Home Visits (Day)	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Home Visits (Night)	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Physician Office/Practice Visits	0.0 Number of visits Standard Deviation 0.24	0.0 Number of visits Standard Deviation 0.39	0.0 Number of visits Standard Deviation 0.10
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Urgent Care/Outpatient Clinic Visits	0.0 Number of visits Standard Deviation 0.07	0.0 Number of visits Standard Deviation 0.07	0.0 Number of visits Standard Deviation 0.00
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Emergency Room Visits	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Inpatient Hospitalization Days (ICU)	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00
Number of the Indicated Unscheduled Asthma-related Healthcare Visits During the Treatment Period Number of Inpatient Hospitalization (GW) Days	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00	0.0 Number of visits Standard Deviation 0.00

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (BL), Week 2 (W2), and Week 4 (W4)

Population: ITT Population. Only those participants available at the specified time points were analyzed.

Participants were given a demonstration of correct inhaler use (using placebo inhalers), and the participants' competence to correctly use the demonstration inhaler was then assessed.

Outcome measures

Outcome measures
Measure	Placebo n=203 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 BL: Used Inhaler Correctly, n=203, 205, 201	194 participants	196 participants	188 participants
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 BL: Used Inhaler Incorrectly, n=203, 205, 201	9 participants	9 participants	13 participants
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 W2: Used Inhaler Correctly, n=190, 203, 200	190 participants	203 participants	200 participants
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 W2: Used Inhaler Incorrectly, n=190, 203, 200	0 participants	0 participants	0 participants
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 W4: Used Inhaler Correctly, n=175, 199, 195	175 participants	199 participants	195 participants
Number of Participants Who Used the Inhaler Correctly or Incorrectly at Baseline, Week 2, and Week 4 W4: Used Inhaler Incorrectly, n=175, 199, 195	0 participants	0 participants	0 participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline, Week 2, and Week 4

Population: ITT Population. Only those participants who used the inhaler incorrectly at the specified time points were analyzed.

Participants were given a demonstration of correct inhaler use (using placebo inhalers), and the participants' competence to correctly use the demonstration inhaler was then assessed based on 3 steps: open the device, inhale the dose, and close the device. If the participants did not perform the maneuvers correctly, the step of the inhaler use that was performed incorrectly by the participants was recorded. The entire procedure was demonstrated once again. and the number of times that the participants required additional instruction (RAI) was recorded.

Outcome measures

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 22 other events

Deaths: 0 deaths

FF 100 µg OD

Serious events: 1 serious events

Other events: 20 other events

Deaths: 0 deaths

FF/VI 100/25 µg OD

Serious events: 0 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=203 participants at risk Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 participants at risk Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 participants at risk Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Gastrointestinal disorders Pancreatitis	0.00% 0/203 • 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.	0.49% 1/205 • 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.	0.00% 0/201 • 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.

Other adverse events

Other adverse events
Measure	Placebo n=203 participants at risk Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=205 participants at risk Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=201 participants at risk Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Infections and infestations Nasopharyngitis	7.4% 15/203 • 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.	6.8% 14/205 • 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.	10.0% 20/201 • 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.
Nervous system disorders Headache	3.9% 8/203 • 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.	4.4% 9/205 • 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.	5.0% 10/201 • 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.

Additional Information

GSK Response Center

GlaxoSmithKline

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

Measure	Placebo n=9 Participants Participants received placebo once daily (OD) in the evening from the dry powder inhaler (DPI) for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF 100 µg OD n=9 Participants Participants received Fluticasone Furoate (FF) 100 microgram (µg) inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 100/25 µg OD n=13 Participants Participants received FF/Vilanterol (VI) 100/25 µg inhalation powder OD in the evening from the DPI for 12 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: Closed the Device Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: Opened the Device Incorrectly, n= 9, 9, 13	8 participants	4 participants	6 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: Inhaled the Dose Incorrectly, n= 9, 9, 13	1 participants	5 participants	6 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: Closed the Device Incorrectly, n= 9, 9, 13	1 participants	0 participants	1 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: RAI once, n= 9, 9, 13	9 participants	5 participants	8 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: RAI 2 Times, n= 9, 9, 13	0 participants	4 participants	4 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: RAI 3 Times, n= 9, 9, 13	0 participants	0 participants	1 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 BL: RAI >3 Times, n= 9, 9, 13	0 participants	0 participants	0 participants
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: Opened the Device Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: Inhaled the Dose Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: Closed the Device Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: RAI once, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: RAI 2 Times, n= 0, 0, 0,	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W2: RAI 3 Times, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 2; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: Opened the Device Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: Inhaled the Dose Incorrectly, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no data can be reported at this time point.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: RAI once, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: RAI 2 Times, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: RAI 3 Times, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.
Number of Participants With the Indicated Reason for Incorrect Inhaler Use and Who Required Additional Instruction the Indicated Number of Times at Baseline, Week 2, and Week 4 W4: RAI >3 Times, n= 0, 0, 0	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.	NA participants No participants used the inhaler incorrectly at Week 4; thus, no participants required additional instruction.