A Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT01009463

Recruitment Status : Completed

First Posted : November 6, 2009

Results First Posted : August 19, 2013

Last Update Posted : November 9, 2017

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
Condition	Pulmonary Disease, Chronic Obstructive
Interventions	Drug: FF/GW642444 Inhalation Powder Drug: GW642444 Inhalation Powder
Enrollment	1626

Participant Flow

Recruitment Details
Pre-assignment Details	At Visit (V) 1, eligible participants (par.) entered a 4-week, open-label Run-In Period (RIP) to establish a stable Baseline. At V 2, eligible par. were randomized to a 52 week, double-blind Treatment Period. 2631 par. were screened, 2071 par. entered the RIP, and 1626 par. were randomized, out of which 1622 received at >= 1 study treatment dose.


Arm/Group Title	FP/SAL 250/50 µg BID	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description	Participants (Par.) were instructed...	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description	Participants (Par.) were instructed to take open label Fluticasone Propionate and Salmeterol (FP/SAL) 250/50 microgram (µg) twice daily (BID) from the ACCUHALER/DISKUS, one inhalation each morning and evening with approximately 12 hours between doses. In addition, all par. were provided supplemental albuterol/salbutamol (metered dose inhaler [MDI] and/or nebules) to be used as needed throughout the study.	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Period Title: 4-week, Open-label Run-In Period
Started	2071	0	0	0	0
Completed	1622	0	0	0	0
Not Completed	449	0	0	0	0
Reason Not Completed
Did Not Meet Continuation Criteria	373	0	0	0	0
Adverse Event	10	0	0	0	0
Lost to Follow-up	6	0	0	0	0
Physician Decision	10	0	0	0	0
Withdrawal by Subject	50	0	0	0	0
Period Title: 52-week, Double-blind Treatment Period
Started	0	409	408	403	402
Completed the Treatment Period	0	295 ^[1]	318 ^[1]	314 ^[1]	303 ^[1]
Completed	0	294 ^[2]	315 ^[2]	312 ^[2]	301 ^[2]
Not Completed	0	115	93	91	101
Reason Not Completed
Adverse Event	0	22	25	29	31
Withdrawal by Subject	0	34	18	17	22
Lack of Efficacy	0	24	16	11	18
Protocol Violation	0	8	7	8	7
Met Protocol-Defined Stopping Criteria	0	10	14	13	10
Study Closed/Terminated	0	2	0	1	0
Lost to Follow-up	0	11	7	6	5
Physician Decision	0	4	6	6	8
[1] Par. completed the treatment period if they attended the last treatment visit (Visit 11). [2] Par. completed the study if they completed the treatment period and safety follow-up phone contact.

Baseline Characteristics

Arm/Group Title		VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD	Total
Arm/Group Description		Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...	Total of all reporting groups
Arm/Group Description		Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Total of all reporting groups
Overall Number of Baseline Participants		409	408	403	402	1622
Baseline Analysis Population Description		[Not Specified]
Baseline Analysis Population Description		[Not Specified]
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	409 participants	408 participants	403 participants	402 participants	1622 participants
		63.6 (9.43)	63.6 (9.06)	63.6 (9.06)	63.8 (9.30)	63.6 (9.21)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	409 participants	408 participants	403 participants	402 participants	1622 participants
	Female	170 41.6%	163 40.0%	172 42.7%	153 38.1%	658 40.6%
	Male	239 58.4%	245 60.0%	231 57.3%	249 61.9%	964 59.4%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	409 participants	408 participants	403 participants	402 participants	1622 participants
White		331	334	332	324	1321
African American/ African Heritage		9	8	6	9	32
Asian		39	37	37	41	154
American Indian or Alaska Native & White		19	16	19	15	69
Asian & White		0	1	0	0	1
American Indian or Alaska Native		10	12	9	12	43
Unknown		1	0	0	1	2

Outcome Measures

1.Primary Outcome


Title	Annual Rate of Moderate and Severe COPD Exacerbations Expressed as Least Square Mean
Description	The annual rate of moderate and severe chronic obstructive pulmonary d...
Description	The annual rate of moderate and severe chronic obstructive pulmonary disease (COPD) exacerbations during the treatment (trt) period (per participant [par.] per year) was assessed. An exacerbation of COPD, is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. The COPD exacerbation was categorized as mild, moderate and severe by the investigator. Mild: worsening symptoms of COPD that were self-managed by the par. without the use of oral corticosteroids or antibiotics; Moderate: worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics; Severe: worsening symptoms of COPD that required treatment with in-patient hospitalization.
Time Frame	From the start of the double blinded study medication until Visit 11 (Week 52)/Early Withdrawal

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all par. randomized who received at least 1 dose of study drug and with available data for analysis. Analysis used a negative binomial regression model with covariates of trt, smoking status at Screening, Baseline pre-dose Day 1 % predicted FEV1 and region and with logarithm of time on trt as an offset variable.


Arm/Group Title	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description:	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description:	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Overall Number of Participants Analyzed	409	408	403	402
Least Squares Mean (95% Confidence Interval) Unit of Measure: Exacerbations per participant per year
	1.05 (0.92 to 1.21)	0.92 (0.80 to 1.06)	0.70 (0.60 to 0.81)	0.90 (0.78 to 1.04)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 50/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.181
	Comments	[Not Specified]
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable.

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 95% 0.72 to 1.06
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 100/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Nominal p-value
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable.

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95% 0.54 to 0.81
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 200/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.109
	Comments	[Not Specified]
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable.

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.70 to 1.04
	Estimation Comments	[Not Specified]

2.Secondary Outcome


Title	Time to First Occurrence of Moderate or Severe COPD Exacerbation
Description	Time to first occurrence analyzed by using a Cox proportional hazards ...
Description	Time to first occurrence analyzed by using a Cox proportional hazards model with covariates of treatment, smoking status at screening (stratum), baseline disease severity (pre-dose Day 1 % predicted FEV1) and centre grouping. An exacerbation of COPD is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptoms (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. A moderate exacerbation is defined as worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics. A severe exacerbation is defined as worsening symptoms of COPD that required treatment with in-patient hospitalization. The number of participants with a moderate or severe COPD exacerbation while on treatment are presented.
Time Frame	From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population


Arm/Group Title	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description:	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description:	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study. )	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Overall Number of Participants Analyzed	409	408	403	402
Measure Type: Number Unit of Measure: Participants
	202	190	160	178

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 50/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.430
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.92
	Confidence Interval	(2-Sided) 95% 0.76 to 1.13
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 100/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.002
	Comments	Nominal p-value
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95% 0.59 to 0.89
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 200/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.114
	Comments	[Not Specified]
	Method	Regression, Cox
	Comments	[Not Specified]

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95% 0.69 to 1.04
	Estimation Comments	[Not Specified]

3.Secondary Outcome


Title	Annual Rate of Exacerbations Requiring Systemic/Oral Corticosteroids Expressed as Least Square Mean
Description	The annual rate of COPD exacerbations during the treatment period (per...
Description	The annual rate of COPD exacerbations during the treatment period (per participant per year) that required systemic/oral corticosteroids was assessed. An exacerbation of COPD is defined as the worsening of two or more major symptoms (dyspnea, sputum volume, sputum purulence [color]) for at least two consecutive days; or the worsening of any one major symptom together with any one of the minor symptom (sore throat, cold, fever without other cause, increased cough, increased wheeze) for at least two consecutive days. The COPD exacerbation was categorized as mild, moderate, and severe by the investigator. Mild: worsening symptoms of COPD that were self-managed by the participant. Mild exacerbations were not associated with the use of oral corticosteroids or antibiotics. Moderate: worsening symptoms of COPD that required treatment with oral corticosteroids and/or antibiotics. Severe: worsening symptoms of COPD that required treatment with in-patient hospitalization.
Time Frame	From the start of the double blind study medication until Visit 11 (Week 52)/Early Withdrawal

Outcome Measure Data

Analysis Population Description


Arm/Group Title	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description:	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description:	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Overall Number of Participants Analyzed	409	408	403	402
Least Squares Mean (95% Confidence Interval) Unit of Measure: Exacerbations per participant per year
	0.84 (0.72 to 0.98)	0.71 (0.60 to 0.83)	0.52 (0.44 to 0.62)	0.68 (0.57 to 0.80)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 50/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.125
	Comments	[Not Specified]
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable.

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.84
	Confidence Interval	(2-Sided) 95% 0.67 to 1.05
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 100/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Nominal p-value
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95% 0.49 to 0.78
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 200/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.064
	Comments	[Not Specified]
	Method	Generalized Linear Model
	Comments	Assuming Negative Binomial distribution with logarithm of time on treatment as an offset variable

Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.81
	Confidence Interval	(2-Sided) 95% 0.64 to 1.01
	Estimation Comments	[Not Specified]

4.Secondary Outcome


Title	Change From Baseline in Trough FEV1 at Week 52 (Visit 11)
Description	Pulmonary function was measured by forced expiratory volume in one sec...
Description	Pulmonary function was measured by forced expiratory volume in one second (FEV1). Trough FEV1 was defined as the 24-hour post-dose FEV1 assessment, which was obtained at each visit. Analysis performed using a repeated measures model with covariates of treatment, smoking status at Screening (stratum), baseline (pre-dose Day 1), centre grouping, Week, Week by Baseline, and Week by treatment interactions.
Time Frame	Baseline to Visit 11 (Week 52)/Early Withdrawal

Outcome Measure Data

Analysis Population Description

ITT Population. Number of participants presented represent those with data available at the time point being presented, however all participants in the ITT population without missing covariate information and with at least one post Baseline measurement are included in the analysis.


Arm/Group Title	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description:	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description:	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
Overall Number of Participants Analyzed	291	308	310	289
Least Squares Mean (Standard Error) Unit of Measure: Liters
	-0.040 (0.0114)	0.000 (0.0112)	0.018 (0.0112)	0.024 (0.0114)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 50/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	0.011
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.041
	Confidence Interval	(2-Sided) 95% 0.009 to 0.072
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 100/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.058
	Confidence Interval	(2-Sided) 95% 0.027 to 0.090
	Estimation Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg QD, FF/VI 200/25 µg QD
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

Statistical Test of Hypothesis	P-Value	<0.001
	Comments	Nominal p-value
	Method	Mixed Models Analysis
	Comments	Restricted maximum likelihood (REML)-based repeated measures approach (MMRM).

Method of Estimation	Estimation Parameter	Least squares mean difference
	Estimated Value	0.064
	Confidence Interval	(2-Sided) 95% 0.033 to 0.096
	Estimation Comments	[Not Specified]

Adverse Events

Time Frame	Serious adverse events (SAEs) and non-serious AEs will be collected from Baseline to the end of the treatment period (up to 52 weeks).
Adverse Event Reporting Description	SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.

Arm/Group Title	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
Arm/Group Description	Participants received a Vilanterol ...	Participants received a Fluticasone...	Participants received a FF/VI 100/2...	Participants received a FF/VI 200/2...
Arm/Group Description	Participants received a Vilanterol (VI) 25 µg dry inhalation powder once daily (QD) in the morning from the Dry Powder Inhaler (DPI) for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a Fluticasone Furoate/Vilanterol (FF/VI) 50/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 100/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.	Participants received a FF/VI 200/25 µg inhalation powder QD in the morning from the DPI for the duration of the 52 weeks. In addition, all participants were provided supplemental albuterol/salbutamol (MDI and/or nebules) to be used as needed throughout the study.
All-Cause Mortality
	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	60/409 (14.67%)	65/408 (15.93%)	56/403 (13.90%)	63/402 (15.67%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	1/402 (0.25%)
Cardiac disorders
Myocardial infarction ^† 1	1/409 (0.24%)	2/408 (0.49%)	2/403 (0.50%)	2/402 (0.50%)
Acute coronary syndrome ^† 1	1/409 (0.24%)	1/408 (0.25%)	1/403 (0.25%)	0/402 (0.00%)
Angina pectoris ^† 1	1/409 (0.24%)	2/408 (0.49%)	0/403 (0.00%)	0/402 (0.00%)
Angina unstable ^† 1	2/409 (0.49%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Acute myocardial infarction ^† 1	1/409 (0.24%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Atrial fibrillation ^† 1	1/409 (0.24%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Cardiac failure congestive ^† 1	1/409 (0.24%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Cardio-respiratory arrest ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Coronary artery stenosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Coronary artery thrombosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Palpitations ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Supraventricular tachycardia ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Arrhythmia ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Cardiac arrest ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Cardiac failure ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Eye disorders
Diplopia ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Gastrointestinal disorders
Rectal haemorrhage ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Upper gastrointestinal haemorrhage ^† 1	1/409 (0.24%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Abdominal pain ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Abdominal pain lower ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Abdominal strangulated hernia ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Constipation ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Diverticulum intestinal ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Gastric ulcer haemorrhage ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Gastritis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Gastritis erosive ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Gastrointestinal haemorrhage ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Gastrooesophageal reflux disease ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Haemorrhoids ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Hiatus hernia ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Ileus ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Melaena ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
AE Term: Salivary gland enlargement ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Small intestinal obstruction ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
General disorders
Chest pain ^† 1	1/409 (0.24%)	2/408 (0.49%)	0/403 (0.00%)	0/402 (0.00%)
Death ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Non-cardiac chest pain ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Hepatobiliary disorders
Bile duct stone ^† 1	1/409 (0.24%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Bile duct obstruction ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Cholecystitis ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Immune system disorders
Anaphylactic shock ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Infections and infestations
Pneumonia ^† 1	2/409 (0.49%)	12/408 (2.94%)	9/403 (2.23%)	12/402 (2.99%)
Cellulitis ^† 1	2/409 (0.49%)	0/408 (0.00%)	4/403 (0.99%)	0/402 (0.00%)
Infective exacerbation of chronic obstructive airway disease ^† 1	2/409 (0.49%)	0/408 (0.00%)	2/403 (0.50%)	0/402 (0.00%)
Bronchitis ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	2/402 (0.50%)
Upper respiratory tract infection ^† 1	2/409 (0.49%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Bronchopneumonia ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	1/402 (0.25%)
Lobar pneumonia ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	1/402 (0.25%)
Lung abscess ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	1/402 (0.25%)
Arthritis bacterial ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Bone tuberculosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Clostridium difficile colitis ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Escherichia sepsis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Gastroenteritis viral ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
H1N1 influenza ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Lower respiratory tract infection ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Mycobacterium avium complex infection ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Pulmonary tuberculosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Pyelonephritis acute ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Respiratory tract infection ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Septic shock ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Tuberculosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Urinary tract infection ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Urinary tract infection bacterial ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Injury, poisoning and procedural complications
Fall ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Foot fracture ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Head injury ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Hip fracture ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Laceration ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Operative haemorrhage ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Pneumothorax traumatic ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Spinal compression fracture ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Toxicity to various agents ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Wrist fracture ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Metabolism and nutrition disorders
Hypokalaemia ^† 1	2/409 (0.49%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Hyperglycaemia ^† 1	0/409 (0.00%)	0/408 (0.00%)	2/403 (0.50%)	0/402 (0.00%)
Diabetes mellitus inadequate control ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Hyponatraemia ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Hypovolaemia ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Ketoacidosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain ^† 1	2/409 (0.49%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Arthritis reactive ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Back pain ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Bursitis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Costochondritis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Intervertebral disc protrusion ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Joint stiffness ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Osteoarthritis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma metastatic ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	1/402 (0.25%)
Squamous cell carcinoma ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	2/402 (0.50%)
Acute lymphocytic leukaemia ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Brain cancer metastatic ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Breast cancer ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Colon cancer ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Laryngeal cancer ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Lung cancer metastatic ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Lung neoplasm malignant ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Malignant hepatobiliary neoplasm ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Malignant melanoma ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Metastases to bone ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Metastases to liver ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Metastases to lung ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Metastatic carcinoma of the bladder ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Non-Hodgkin's lymphoma ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Small cell carcinoma ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Nervous system disorders
Cerebrovascular accident ^† 1	0/409 (0.00%)	0/408 (0.00%)	2/403 (0.50%)	3/402 (0.75%)
Syncope ^† 1	2/409 (0.49%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Carotid artery aneurysm ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Carotid artery stenosis ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Convulsion ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Dizziness ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Loss of consciousness ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Metabolic encephalopathy ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Psychiatric disorders
Depression ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Depression suicidal ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Renal and urinary disorders
Renal failure acute ^† 1	0/409 (0.00%)	3/408 (0.74%)	0/403 (0.00%)	0/402 (0.00%)
Calculus urinary ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Haematuria ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Urethral stenosis ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Reproductive system and breast disorders
Benign prostatic hyperplasia ^† 1	2/409 (0.49%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease ^† 1	28/409 (6.85%)	27/408 (6.62%)	26/403 (6.45%)	30/402 (7.46%)
Acute respiratory failure ^† 1	0/409 (0.00%)	3/408 (0.74%)	3/403 (0.74%)	2/402 (0.50%)
Pleural effusion ^† 1	0/409 (0.00%)	0/408 (0.00%)	2/403 (0.50%)	0/402 (0.00%)
Pneumothorax ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	2/402 (0.50%)
Respiratory failure ^† 1	0/409 (0.00%)	2/408 (0.49%)	0/403 (0.00%)	0/402 (0.00%)
Acute pulmonary oedema ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Asthma ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Bronchitis chronic ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Bronchopleural fistula ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Hypoxia ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Pulmonary embolism ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Pulmonary oedema ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Vocal cord disorder ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Vascular disorders
Hypertension ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	1/402 (0.25%)
Aortic aneurysm rupture ^† 1	0/409 (0.00%)	0/408 (0.00%)	0/403 (0.00%)	1/402 (0.25%)
Haematoma ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Hypertensive crisis ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
Peripheral arterial occlusive disease ^† 1	0/409 (0.00%)	0/408 (0.00%)	1/403 (0.25%)	0/402 (0.00%)
Shock ^† 1	1/409 (0.24%)	0/408 (0.00%)	0/403 (0.00%)	0/402 (0.00%)
Shock haemorrhagic ^† 1	0/409 (0.00%)	1/408 (0.25%)	0/403 (0.00%)	0/402 (0.00%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	VI 25 µg QD	FF/VI 50/25 µg QD	FF/VI 100/25 µg QD	FF/VI 200/25 µg QD
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	197/409 (48.17%)	227/408 (55.64%)	221/403 (54.84%)	225/402 (55.97%)
Gastrointestinal disorders
Diarrhoea ^† 1	15/409 (3.67%)	12/408 (2.94%)	8/403 (1.99%)	15/402 (3.73%)
Nausea ^† 1	10/409 (2.44%)	24/408 (5.88%)	7/403 (1.74%)	10/402 (2.49%)
General disorders
Pyrexia ^† 1	5/409 (1.22%)	17/408 (4.17%)	10/403 (2.48%)	8/402 (1.99%)
Infections and infestations
Nasopharyngitis ^† 1	54/409 (13.20%)	58/408 (14.22%)	60/403 (14.89%)	76/402 (18.91%)
Upper respiratory tract infection ^† 1	45/409 (11.00%)	47/408 (11.52%)	51/403 (12.66%)	39/402 (9.70%)
Oral candidiasis ^† 1	21/409 (5.13%)	39/408 (9.56%)	34/403 (8.44%)	36/402 (8.96%)
Bronchitis ^† 1	20/409 (4.89%)	13/408 (3.19%)	21/403 (5.21%)	23/402 (5.72%)
Sinusitis ^† 1	17/409 (4.16%)	21/408 (5.15%)	22/403 (5.46%)	13/402 (3.23%)
Pneumonia ^† 1	10/409 (2.44%)	17/408 (4.17%)	16/403 (3.97%)	16/402 (3.98%)
Influenza ^† 1	21/409 (5.13%)	10/408 (2.45%)	13/403 (3.23%)	13/402 (3.23%)
Pharyngitis ^† 1	14/409 (3.42%)	8/408 (1.96%)	14/403 (3.47%)	16/402 (3.98%)
Urinary tract infection ^† 1	7/409 (1.71%)	16/408 (3.92%)	10/403 (2.48%)	17/402 (4.23%)
Rhinitis ^† 1	6/409 (1.47%)	9/408 (2.21%)	10/403 (2.48%)	15/402 (3.73%)
Oropharyngeal candidiasis ^† 1	2/409 (0.49%)	14/408 (3.43%)	7/403 (1.74%)	6/402 (1.49%)
Musculoskeletal and connective tissue disorders
Back pain ^† 1	30/409 (7.33%)	21/408 (5.15%)	24/403 (5.96%)	20/402 (4.98%)
Arthralgia ^† 1	13/409 (3.18%)	13/408 (3.19%)	16/403 (3.97%)	13/402 (3.23%)
Nervous system disorders
Headache ^† 1	30/409 (7.33%)	27/408 (6.62%)	25/403 (6.20%)	34/402 (8.46%)
Dizziness ^† 1	8/409 (1.96%)	13/408 (3.19%)	5/403 (1.24%)	3/402 (0.75%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	14/409 (3.42%)	21/408 (5.15%)	16/403 (3.97%)	13/402 (3.23%)
Oropharyngeal pain ^† 1	13/409 (3.18%)	7/408 (1.72%)	14/403 (3.47%)	13/402 (3.23%)
Dyspnoea ^† 1	10/409 (2.44%)	13/408 (3.19%)	6/403 (1.49%)	4/402 (1.00%)
Vascular disorders
Hypertension ^† 1	6/409 (1.47%)	15/408 (3.68%)	19/403 (4.71%)	12/402 (2.99%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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.

Results Point of Contact

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Name/Title:	GSK Response Center
Organization:	GlaxoSmithKline
Phone:	866-435-7343

Publications:

Dransfield MT, Bourbeau J, Jones PW, Hanania NA, Mahler DA, Vestbo J, Wachtel A, Martinez FJ, Barnhart F, Sanford L, Lettis S, Crim C, Calverley PM. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD: two replicate double-blind, parallel-group, randomised controlled trials. Lancet Respir Med. 2013 May;1(3):210-23. doi: 10.1016/S2213-2600(13)70040-7. Epub 2013 Apr 12. Erratum in: Lancet Respir Med. 2013 May;1(3):186.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Largajolli A, Beerahee M, Yang S. Bayesian approach to investigate a two-state mixed model of COPD exacerbations. J Pharmacokinet Pharmacodyn. 2019 Aug;46(4):371-384. doi: 10.1007/s10928-019-09643-6. Epub 2019 Jun 13. Erratum in: J Pharmacokinet Pharmacodyn. 2019 Dec;46(6):627.

Hinds DR, DiSantostefano RL, Le HV, Pascoe S. Identification of responders to inhaled corticosteroids in a chronic obstructive pulmonary disease population using cluster analysis. BMJ Open. 2016 Jun 1;6(6):e010099. doi: 10.1136/bmjopen-2015-010099.

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Layout table for additonal information

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT01009463
Other Study ID Numbers:	102871
First Submitted:	November 5, 2009
First Posted:	November 6, 2009
Results First Submitted:	May 30, 2013
Results First Posted:	August 19, 2013
Last Update Posted:	November 9, 2017

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