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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01054885
• Collaborator: (none)
• Enrollment: 1,226
• Locations: 149
• Arms: 6
• Duration (Months): 15.7
• Patients Per Site: 8.2
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The Purpose of this study is to assess the efficacy and safety of two strengths of the FF/GW642444 Inhalation Powder in subject with Chronic Obstructive Pulmonary Disease (COPD)

Condition or Disease	Intervention/Treatment	Phase
Pulmonary Disease, Chronic Obstructive	Drug: FF Inhalation Powder; Drug: FF/GW642444 Inhalation Powder; Drug: GW642444 Inhalation Powder; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1226 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A 24-Week Study to Evaluate the Efficacy and Safety of Fluticasone Furoate (FF)/GW642444 Inhalation Powder and the Individual Components Delivered Once Daily (AM) Via a Novel Dry Powder Inhaler Compared With Placebo in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
• Study Start Date: Oct 19, 2009
• Actual Primary Completion Date: Feb 1, 2011
• Actual Study Completion Date: Feb 8, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fluticasone Furoate Inhalation Powder Inhaled Corticosteroid (ICS)	Drug: FF Inhalation Powder; Inhaled Corticosteroid (ICS)
Experimental: FF Inhalation Pwdr Inhaled Corticosteroid (ICS)	Drug: FF Inhalation Powder; Inhaled Corticosteroid (ICS)
Experimental: Fluticasone Furoate/GW642444 Inhalation Powder Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA)	Drug: FF/GW642444 Inhalation Powder; Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA) for COPD
Experimental: FF/GW642444 Inhalation Pwdr Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA)	Drug: FF/GW642444 Inhalation Powder; Inhaled Corticosteroid (ICS)/ Long Acting Beta Agonist(LABA) for COPD
Experimental: GW642444 Inhalation Powder Long Acting Beta Agonist(LABA)	Drug: GW642444 Inhalation Powder; Long Acting Beta Agonist(LABA)
Placebo Comparator: Placebo Placebo	Drug: Placebo; Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Weighted Mean FEV1 Over 0-4 Hours (h) Post-dose at Day 168 [Baseline (BL) to Day 168]

   Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Serial FEV1 measurements were taken electronically by spirometry at BL, weeks 2, 8, 12, and 84 (Day 168). Weighted mean (WM) was calculated using the 0 - 4 h post-dose FEV1 measurements that included the pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits:23 and 24 h after previous morning dose) and post-dose (5, 15, and 30 min and 1, 2, and 4 h) assessments. BL FEV1 is the mean of the two assessments made 30 and 5 min pre-dose at Day 1. WM change from BL was the WM at the visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL- mean of the two assessments made 30 and 5 min pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.

2. Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 169 [Baseline to Day 169]

   Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 7, 14, 28, 56, 84, 112, 140, 168, and 169. BL was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.

Secondary Outcome Measures

1. Change From Baseline in Chronic Respiratory Disease Questionnaire Self-administered Standardized (CRQ-SAS) Dyspnea Score at Day 168 [Baseline to Day 168]

   Considered an 'Other' endpoint by FDA. CRQ-SAS measures 4 domains (mastery, fatigue, emotional function, and dyspnea) of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately. Current assessment was done only for dyspnea domain. BL scores are the derived scores for each domain and total at Day 1 pre-dose. Change from BL was calculated as the average at each visit minus the BL value. Analysis performed used a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL (derived scores at Day 1 pre-dose), centre grouping, Day, Day by BL and Day by treatment interactions.

2. Change From Baseline in Peak Post-dose FEV1 (0-4 Hour) on Day 1 [Baseline and Day 1]

   Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. BL FEV1 is defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. If one of these two assessments was missing then BL was defined as the single pre-dose FEV1 value on Day 1. Peak post-dose FEV1 (0-4 hours) is the maximum post-dose FEV1 recorded over the nominal timepoints of 5, 15 and 30 min, 1, 2 and 4 hours post the Day 1 dose. Change from BL is calculated as the peak post-dose FEV1 (0-4 hour) on Day 1 minus BL FEV1. Analysis performed used an Analysis of Covariance (ANCOVA) model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, and centre grouping.

3. Time to Onset (Increase of 100 Milliliter [mL] From Baseline in 0-4 Hours Post-dose FEV1) on Treatment Day 1 [Baseline and Day 1]

   Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. Time to onset on Treatment Day 1 is defined as a 100 mL increase from Baseline in FEV1. Time to increase of 100 mL from Baseline was calculated over the 5, 15, 30 minutes, and 1, 2, and 4 hours time points. A participant who had at least one post-dose FEV1 on Day 1, but did not achieve a 100 mL or more increase from Baseline at any scheduled time-point at which FEV1 was assessed up to and including 4 hours was censored.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type of subject: outpatient

• Informed consent: Subjects must give their signed and dated written informed consent to participate.

• Gender: Male or female subjects A female is eligible to enter and participate in the study if she is of:

• Non-child bearing potential OR

• Child bearing potential, has a negative pregnancy test at screening, and agrees to one of the acceptable contraceptive methods defined in the protocol

• Age: ≥40 years of age at Screening (Visit 1)

• COPD diagnosis: Subjects with a clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society [Celli, 2004]

• Tobacco use: Subjects with a current or prior history of ≥10 pack-years of cigarette smoking at Screening (Visit 1).

• Severity of Disease: Subjects with a Screening (Visit 1) measured post-albuterol/salbutamol:

• FEV1/FVC ratio of ≤0.70 and

• FEV1 ≤70% of predicted normal values

• Dyspnea: Achieved a score of ≥2 on the Modified Medical Research Council Dyspnea Scale (mMRC) at Screening (Visit 1).

Exclusion Criteria:

Subjects meeting any of the following criteria must not be enrolled in the study:

• Pregnancy: Women who are pregnant or lactating or are planning on becoming pregnant during the study.

• Asthma: Subjects with a current diagnosis of asthma

• α1-antitrypsin deficiency: Subjects with α1-antitrypsin deficiency as the underlying cause of COPD

• Other respiratory disorders: Subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases

• Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Screening (Visit 1)

• Chest X-ray (or CT scan): Subjects with a chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities not believed to be due to the presence of COPD.

• Hospitalization: Subjects who are hospitalized due to poorly controlled COPD within 12 weeks of Visit 1.

• Poorly controlled COPD: Subjects with poorly controlled COPD, defined as the occurrence of the following in the 6 weeks prior to Visit 1: Acute worsening of COPD that is managed by subject with corticosteroids or antibiotics or that requires treatment prescribed by a physician.

• Lower respiratory tract infection: Subjects with lower respiratory tract infection that required the use of antibiotics within 6 weeks prior to Visit 1.

• Other diseases/abnormalities: Subjects with historical or current evidence of clinically significant cardiovascular (i.e., pacemaker), neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled.

• Peptic Ulcer disease: Subjects with clinically significant peptic ulcer disease that is uncontrolled.

• Hypertension: Subjects with clinically significant hypertension that is uncontrolled.

• Cancer: Subjects with carcinoma that has not been in complete remission for at least 5 years. Carcinoma in situ of the cervix, squamous cell carcinoma and basal cell carcinoma of the skin would not be excluded if the subject has been considered cured within 5 years since diagnosis.

• Drug/food allergy: Subjects with a history of hypersensitivity to any of the study medication or components of the inhalation powder

• Drug/alcohol abuse: Subjects with a known or suspected history of alcohol or drug abuse within the last 2 years

• Medication prior to spirometry: Subjects who are medically unable to withhold their albuterol/salbutamol and/or their ipratropium 4 hours prior to spirometry testing at each study visit

• Additional medication: Use of certain medications such as bronchodilators and corticosteroids for the protocol-specified times prior to Visit 1 (the Investigator will discuss the specific medications)

• Oxygen therapy: Subjects receiving treatment with long-term oxygen therapy (LTOT) or nocturnal oxygen therapy required for greater than 12 hours a day. Oxygen prn use (i.e., ≤12 hours per day) is not exclusionary.

• Sleep apnea: Subjects with clinically significant sleep apnea who require use of continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.

• Pulmonary rehabilitation: Subjects who have participated in the acute phase of a Pulmonary Rehabilitation Program within 4 weeks prior to Screening (Visit 1) or who will enter the acute phase of a Pulmonary Rehabilitation Program during the study.

• Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

• Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.

• Prior use of study medication/other investigational drugs

• Affiliation with investigator site: Study investigators, sub-investigators, study coordinators, employees of a participating investigator or immediate family members of the aforementioned are excluded from participating in this study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35235
2	GSK Investigational Site	Jasper	Alabama	United States	35501
3	GSK Investigational Site	Lakewood	California	United States	90712
4	GSK Investigational Site	Long Beach	California	United States	90808
5	GSK Investigational Site	Los Angeles	California	United States	90048
6	GSK Investigational Site	Monterey Park	California	United States	91754
7	GSK Investigational Site	National City	California	United States	91950
8	GSK Investigational Site	Oxnard	California	United States	93030-5841
9	GSK Investigational Site	San Diego	California	United States	92120
10	GSK Investigational Site	Santa Monica	California	United States	90404
11	GSK Investigational Site	Wilmington	Delaware	United States	19805
12	GSK Investigational Site	Bay Pines	Florida	United States	33744
13	GSK Investigational Site	Brandon	Florida	United States	33511
14	GSK Investigational Site	Clearwater	Florida	United States	33756
15	GSK Investigational Site	Cocoa	Florida	United States	32927
16	GSK Investigational Site	Fort Lauderdale	Florida	United States	33316
17	GSK Investigational Site	Pensacola	Florida	United States	32503
18	GSK Investigational Site	Decatur	Georgia	United States
19	GSK Investigational Site	Gainesville	Georgia	United States
20	GSK Investigational Site	Martinez	Georgia	United States	30907
21	GSK Investigational Site	Lenexa	Kansas	United States	66215
22	GSK Investigational Site	Wheaton	Maryland	United States	20902
23	GSK Investigational Site	Saint Charles	Missouri	United States	63301
24	GSK Investigational Site	Cherry Hill	New Jersey	United States	08003
25	GSK Investigational Site	Ocean City	New Jersey	United States	7712
26	GSK Investigational Site	Brooklyn	New York	United States	11229
27	GSK Investigational Site	Elizabeth City	North Carolina	United States	27909
28	GSK Investigational Site	Statesville	North Carolina	United States	28625
29	GSK Investigational Site	Cincinnati	Ohio	United States	45231
30	GSK Investigational Site	Dayton	Ohio	United States	45439
31	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73103
32	GSK Investigational Site	Tulsa	Oklahoma	United States	74136-8303
33	GSK Investigational Site	Medford	Oregon	United States	97504
34	GSK Investigational Site	Portland	Oregon	United States	97213
35	GSK Investigational Site	Columbia	South Carolina	United States	29203
36	GSK Investigational Site	Easley	South Carolina	United States	29640
37	GSK Investigational Site	Gaffney	South Carolina	United States	29340
38	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
39	GSK Investigational Site	Seneca	South Carolina	United States	29678
40	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
41	GSK Investigational Site	Union	South Carolina	United States	29379
42	GSK Investigational Site	Johnson City	Tennessee	United States	37601
43	GSK Investigational Site	New Tazewell	Tennessee	United States	37825
44	GSK Investigational Site	Boerne	Texas	United States	78006
45	GSK Investigational Site	Corsicana	Texas	United States	75110
46	GSK Investigational Site	Kingwood	Texas	United States	77339
47	GSK Investigational Site	Temple	Texas	United States	76508
48	GSK Investigational Site	Fredericksburg	Virginia	United States	22401
49	GSK Investigational Site	Morgantown	West Virginia	United States	26505
50	GSK Investigational Site	Cipolletti	Río Negro	Argentina	R8324EMB
51	GSK Investigational Site	Buenos Aires		Argentina	C1425BEN
52	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1121ABE
53	GSK Investigational Site	San Miguel de Tucumán		Argentina	4000
54	GSK Investigational Site	Brno		Czechia	625 00
55	GSK Investigational Site	Jindrichuv Hradec		Czechia	377 01
56	GSK Investigational Site	Kralupy nad Vltavou		Czechia	278 01
57	GSK Investigational Site	Liberec		Czechia	460 01
58	GSK Investigational Site	Ostrava - Poruba		Czechia	70868
59	GSK Investigational Site	Plzen		Czechia	301 00
60	GSK Investigational Site	Plzen		Czechia	323 00
61	GSK Investigational Site	Praha 8		Czechia	180 81
62	GSK Investigational Site	Praha 8		Czechia	182 00
63	GSK Investigational Site	Rokycany		Czechia	337 01
64	GSK Investigational Site	Tabor		Czechia	390 19
65	GSK Investigational Site	Muenchen	Bayern	Germany	80339
66	GSK Investigational Site	Darmstadt	Hessen	Germany	64287
67	GSK Investigational Site	Frankfurt	Hessen	Germany	60389
68	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
69	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
70	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19055
71	GSK Investigational Site	Koeln	Nordrhein-Westfalen	Germany	51069
72	GSK Investigational Site	Rhaunen	Rheinland-Pfalz	Germany	55624
73	GSK Investigational Site	Dresden	Sachsen	Germany	01307
74	GSK Investigational Site	Leipzg	Sachsen	Germany	04109
75	GSK Investigational Site	Radebeul	Sachsen	Germany	01445
76	GSK Investigational Site	Geesthacht	Schleswig-Holstein	Germany	21502
77	GSK Investigational Site	Berlin		Germany	10117
78	GSK Investigational Site	Berlin		Germany	10367
79	GSK Investigational Site	Berlin		Germany	10717
80	GSK Investigational Site	Berlin		Germany	10787
81	GSK Investigational Site	Berlin		Germany	12043
82	GSK Investigational Site	Berlin		Germany	12203
83	GSK Investigational Site	Berlin		Germany	13086
84	GSK Investigational Site	Berlin		Germany	13125
85	GSK Investigational Site	Berlin		Germany	13581
86	GSK Investigational Site	Berlin		Germany	14057
87	GSK Investigational Site	Hamburg		Germany	22143
88	GSK Investigational Site	Hamburg		Germany	22299
89	GSK Investigational Site	Hamburg		Germany	22335
90	GSK Investigational Site	Chiba		Japan	296-8602
91	GSK Investigational Site	Ehime		Japan	791-0281
92	GSK Investigational Site	Fukuoka		Japan	811-3195
93	GSK Investigational Site	Ibaraki		Japan	306-0433
94	GSK Investigational Site	Kyoto		Japan	602-8026
95	GSK Investigational Site	Kyoto		Japan	612-0026
96	GSK Investigational Site	Mie		Japan	514-1101
97	GSK Investigational Site	Okinawa		Japan	901-2132
98	GSK Investigational Site	Okinawa		Japan	904-2143
99	GSK Investigational Site	Osaka		Japan	530-0001
100	GSK Investigational Site	Osaka		Japan	591-8555
101	GSK Investigational Site	Shizuoka		Japan	434-8511
102	GSK Investigational Site	Tokyo		Japan	158-0083
103	GSK Investigational Site	Czestochowa		Poland	42-200
104	GSK Investigational Site	Gdansk		Poland	80-952
105	GSK Investigational Site	Gidle		Poland	97-540
106	GSK Investigational Site	Gizycko		Poland	11-500
107	GSK Investigational Site	Lomza		Poland	18-400
108	GSK Investigational Site	Piekary Slaskie		Poland	41-940
109	GSK Investigational Site	Szczecin		Poland	71-124
110	GSK Investigational Site	Warszawa		Poland	01-138
111	GSK Investigational Site	Warszawa		Poland	02-097
112	GSK Investigational Site	Brasov		Romania	500112
113	GSK Investigational Site	Bucharest		Romania	011794
114	GSK Investigational Site	Bucharest		Romania	020125
115	GSK Investigational Site	Bucharest		Romania	020201
116	GSK Investigational Site	Bucharest		Romania	030317
117	GSK Investigational Site	Bucharest		Romania	031298
118	GSK Investigational Site	Bucharest		Romania	050159
119	GSK Investigational Site	Bucuresti		Romania	010816
120	GSK Investigational Site	Bucuresti		Romania	70000
121	GSK Investigational Site	Cluj-Napoca		Romania	400349
122	GSK Investigational Site	Cluj-Napoca		Romania	400371
123	GSK Investigational Site	Constanta		Romania	900002
124	GSK Investigational Site	Deva		Romania	330160
125	GSK Investigational Site	Iasi		Romania	700115
126	GSK Investigational Site	Popesti Leordeni		Romania	077160
127	GSK Investigational Site	Suceava		Romania	720284
128	GSK Investigational Site	Timisoara		Romania	300310
129	GSK Investigational Site	Chelyabinsk		Russian Federation	454106
130	GSK Investigational Site	Ivanovo		Russian Federation	153005
131	GSK Investigational Site	Kazan		Russian Federation	420015
132	GSK Investigational Site	Kemerovo		Russian Federation	650000
133	GSK Investigational Site	Krasnoyarsk		Russian Federation	660022
134	GSK Investigational Site	Moscow		Russian Federation	105077
135	GSK Investigational Site	Moscow		Russian Federation	119 048
136	GSK Investigational Site	Moscow		Russian Federation	127018
137	GSK Investigational Site	Saint-Petersburg		Russian Federation	193231
138	GSK Investigational Site	Saint-Petersburg		Russian Federation	194354
139	GSK Investigational Site	Yaroslavl		Russian Federation
140	GSK Investigational Site	Dnipropetrovsk		Ukraine	49051
141	GSK Investigational Site	Kharkiv		Ukraine	61035
142	GSK Investigational Site	Kiev		Ukraine	03680
143	GSK Investigational Site	Kyiv		Ukraine	01114
144	GSK Investigational Site	Kyiv		Ukraine	02091
145	GSK Investigational Site	Kyiv		Ukraine	03038
146	GSK Investigational Site	Kyiv		Ukraine	03115
147	GSK Investigational Site	Odesa		Ukraine	65117
148	GSK Investigational Site	Simferopol		Ukraine	95043
149	GSK Investigational Site	Vinnytsia		Ukraine	21029

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

• Martinez FJ, Boscia J, Feldman G, Scott-Wilson C, Kilbride S, Fabbri L, Crim C, Calverley PM. Fluticasone furoate/vilanterol (100/25; 200/25 μg) improves lung function in COPD: a randomised trial. Respir Med. 2013 Apr;107(4):550-9. doi: 10.1016/j.rmed.2012.12.016. Epub 2013 Jan 16. Erratum in: Respir Med. 2013 Dec;107(12):2092-3.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01054885
• Other Study ID Numbers: 112207
• First Posted: Jan 22, 2010
• Last Update Posted: Jan 24, 2018
• Last Verified: Jan 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: COPD; Chronic Obstructive Pulmonary Disease; Efficacy; FEV1; Safety
• Additional relevant MeSH terms: Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Pre-assignment Detail	Eligible participants (par.) completed a 2-week single-blind (placebo) Run-in Period (RIP) to assess Baseline rescue use, symptoms, disease stability. Par. were then randomized to a 24-week Treatment Period. A total of 1909 par. were screened, 1577 entered the RIP, of whom 1226 were randomized, 1224 received at least one dose of study medication.

Arm/Group Title	Placebo Run-in	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo once daily (OD) in the morning for 2 weeks.	Participants received placebo once daily (OD) in the morning from the dry powder inhaler (DPI) for 24 weeks.	Participants received Fluticasone Furoate (FF) 100 micrograms (µg) OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received Vilanterol (VI [GW642444]) 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Period Title: 2-week, Single-blind Run-In Period
STARTED	1577	0	0	0	0	0	0
COMPLETED	1226	0	0	0	0	0	0
NOT COMPLETED	351	0	0	0	0	0	0
Period Title: 2-week, Single-blind Run-In Period
STARTED	0	205	204	203	203	204	205
COMPLETED	0	146	155	160	161	144	158
NOT COMPLETED	0	59	49	43	42	60	47

Baseline Characteristics

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD	Total
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.	Total of all reporting groups
Overall Participants	205	204	203	203	204	205	1224
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	61.9 (8.14)	61.8 (8.28)	61.8 (9.02)	61.2 (8.62)	61.9 (8.79)	61.1 (8.67)	61.6 (8.58)
Sex: Female, Male (Count of Participants)
Female	53 25.9%	54 26.5%	52 25.6%	52 25.6%	60 29.4%	68 33.2%	339 27.7%
Male	152 74.1%	150 73.5%	151 74.4%	151 74.4%	144 70.6%	137 66.8%	885 72.3%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage (HER)	0 0%	2 1%	5 2.5%	3 1.5%	4 2%	2 1%	16 1.3%
American Indian or Alaska Native	0 0%	0 0%	1 0.5%	0 0%	2 1%	0 0%	3 0.2%
Japanese/East Asian HER/South East Asian HER	8 3.9%	5 2.5%	14 6.9%	4 2%	8 3.9%	11 5.4%	50 4.1%
White	197 96.1%	197 96.6%	183 90.1%	196 96.6%	190 93.1%	192 93.7%	1155 94.4%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Weighted Mean FEV1 Over 0-4 Hours (h) Post-dose at Day 168
Description	Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Serial FEV1 measurements were taken electronically by spirometry at BL, weeks 2, 8, 12, and 84 (Day 168). Weighted mean (WM) was calculated using the 0 - 4 h post-dose FEV1 measurements that included the pre-dose (Day 1: 30 minutes [min] and 5 min prior to dosing; other serial visits:23 and 24 h after previous morning dose) and post-dose (5, 15, and 30 min and 1, 2, and 4 h) assessments. BL FEV1 is the mean of the two assessments made 30 and 5 min pre-dose at Day 1. WM change from BL was the WM at the visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL- mean of the two assessments made 30 and 5 min pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.
Time Frame	Baseline (BL) to Day 168

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Measure Participants	147	154	162	160	146	158
Least Squares Mean (Standard Error) [Liters]	-0.012 (0.0189)	0.034 (0.0187)	0.029 (0.0185)	0.173 (0.0184)	0.202 (0.0190)	0.197 (0.0184)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 100 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.085
	Comments
	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	0.046
	Confidence Interval	(2-Sided) 95%; -0.006 to 0.098
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 200 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.123
	Comments
	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%; -0.011 to 0.093
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI 25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	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	0.185
	Confidence Interval	(2-Sided) 95%; 0.133 to 0.237
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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	0.214
	Confidence Interval	(2-Sided) 95%; 0.161 to 0.266
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	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	0.209
	Confidence Interval	(2-Sided) 95%; 0.157 to 0.261
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	FF 100 µg OD, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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	0.168
	Confidence Interval	(2-Sided) 95%; 0.116 to 0.220
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	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	0.168
	Confidence Interval	(2-Sided) 95%; 0.117 to 0.219
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg OD, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.274
	Comments
	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	0.029
	Confidence Interval	(2-Sided) 95%; -0.023 to 0.081
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.357
	Comments
	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	0.024
	Confidence Interval	(2-Sided) 95%; -0.027 to 0.075
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Clinic Visit Trough (Pre-bronchodilator and Pre-dose) FEV1 at Day 169
Description	Co-Primary Endpoint: Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 7, 14, 28, 56, 84, 112, 140, 168, and 169. BL was defined as the mean of the assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Trough FEV1 was defined as the mean of the FEV1 values obtained 23 and 24 hours after previous morning's dosing. Change from BL was calculated as the average at each visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, centre grouping, Day, Day by BL and Day by treatment interactions.
Time Frame	Baseline to Day 169

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Measure Participants	142	148	155	150	137	153
Least Squares Mean (Standard Error) [Liters]	0.004 (0.0189)	0.048 (0.0187)	0.012 (0.0185)	0.103 (0.0185)	0.148 (0.0191)	0.135 (0.0185)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 100 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	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	0.044
	Confidence Interval	(2-Sided) 95%; -0.008 to 0.097
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF 200 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.756
	Comments
	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	0.008
	Confidence Interval	(2-Sided) 95%; -0.044 to 0.060
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, VI 25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	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	0.100
	Confidence Interval	(2-Sided) 95%; 0.048 to 0.151
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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	0.144
	Confidence Interval	(2-Sided) 95%; 0.091 to 0.197
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Placebo, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	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	0.131
	Confidence Interval	(2-Sided) 95%; 0.080 to 0.183
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	FF 100 µg OD, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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	0.100
	Confidence Interval	(2-Sided) 95%; 0.047 to 0.152
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	FF 200 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
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	0.123
	Confidence Interval	(2-Sided) 95%; 0.072 to 0.174
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg OD, FF/VI 100/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.093
	Comments
	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	0.045
	Confidence Interval	(2-Sided) 95%; -0.008 to 0.097
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	VI 25 µg OD, FF/VI 200/25 µg OD
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments
	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	0.032
	Confidence Interval	(2-Sided) 95%; -0.019 to 0.083
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Chronic Respiratory Disease Questionnaire Self-administered Standardized (CRQ-SAS) Dyspnea Score at Day 168
Description	Considered an 'Other' endpoint by FDA. CRQ-SAS measures 4 domains (mastery, fatigue, emotional function, and dyspnea) of functioning of participants with COPD: mastery (amount of control the participant feels he/she has over COPD symptoms); fatigue (how tired the participant feels); emotional function (how anxious/depressed the participant feels); and dyspnea (how short of breath the participant feels during physical activities). Each domain is measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Each domain score is calculated separately. Current assessment was done only for dyspnea domain. BL scores are the derived scores for each domain and total at Day 1 pre-dose. Change from BL was calculated as the average at each visit minus the BL value. Analysis performed used a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL (derived scores at Day 1 pre-dose), centre grouping, Day, Day by BL and Day by treatment interactions.
Time Frame	Baseline to Day 168

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represent those with data available at the time point being presented; however, all par. in the ITT population without missing covariate information and with at least one post BL measurement are included in the analysis

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Measure Participants	146	154	161	161	146	156
Least Squares Mean (Standard Error) [Scores on a scale]	0.21 (0.077)	0.10 (0.076)	0.21 (0.075)	0.28 (0.075)	0.45 (0.078)	0.31 (0.075)

4. Secondary Outcome

Title	Change From Baseline in Peak Post-dose FEV1 (0-4 Hour) on Day 1
Description	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. BL FEV1 is defined as the mean of the assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. If one of these two assessments was missing then BL was defined as the single pre-dose FEV1 value on Day 1. Peak post-dose FEV1 (0-4 hours) is the maximum post-dose FEV1 recorded over the nominal timepoints of 5, 15 and 30 min, 1, 2 and 4 hours post the Day 1 dose. Change from BL is calculated as the peak post-dose FEV1 (0-4 hour) on Day 1 minus BL FEV1. Analysis performed used an Analysis of Covariance (ANCOVA) model with covariates of treatment, smoking status at screening (stratum), BL - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, and centre grouping.
Time Frame	Baseline and Day 1

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of study medication. Only those participants available at the indicated time point and without missing covariate information were analyzed.

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	FVI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Measure Participants	204	203	202	201	203	205
Least Squares Mean (Standard Error) [Liters]	0.120 (0.0108)	0.144 (0.0109)	0.127 (0.0109)	0.267 (0.0109)	0.272 (0.0109)	0.261 (0.0108)

5. Secondary Outcome

Title	Time to Onset (Increase of 100 Milliliter [mL] From Baseline in 0-4 Hours Post-dose FEV1) on Treatment Day 1
Description	Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled from the lungs in one second. Baseline FEV1 is defined as the mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1. Time to onset on Treatment Day 1 is defined as a 100 mL increase from Baseline in FEV1. Time to increase of 100 mL from Baseline was calculated over the 5, 15, 30 minutes, and 1, 2, and 4 hours time points. A participant who had at least one post-dose FEV1 on Day 1, but did not achieve a 100 mL or more increase from Baseline at any scheduled time-point at which FEV1 was assessed up to and including 4 hours was censored.
Time Frame	Baseline and Day 1

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all randomized participants who received at least one dose of study medication. Only those participants available at the indicated time point were assessed.

Arm/Group Title	Placebo	FF 100 µg OD	FF 200 µg OD	VI 25 µg OD	FF/VI 100/25 µg OD	FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.	Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.	Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.	Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.	Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
Measure Participants	204	203	202	201	203	205
Median (Full Range) [Minutes]	NA	231	242	17	16	17

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication through the end of treatment (up to Week 24).
Adverse Event Reporting Description	An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Arm/Group Title	Placebo		FF 100 µg OD		FF 200 µg OD		VI 25 µg OD		FF/VI 100/25 µg OD		FF/VI 200/25 µg OD
Arm/Group Description	Participants received placebo OD in the morning from the DPI for 24 weeks.		Participants received FF 100 µg OD in the morning from the DPI for 24 weeks.		Participants received FF 200 µg OD in the morning from the DPI for 24 weeks.		Participants received VI 25 µg OD in the morning from the DPI for 24 weeks.		Participants received FF/VI 100/25 µg OD in the morning from the DPI for 24 weeks.		Participants received FF/VI 200/25 µg OD in the morning from the DPI for 24 weeks.
All Cause Mortality
	Placebo		FF 100 µg OD		FF 200 µg OD		VI 25 µg OD		FF/VI 100/25 µg OD		FF/VI 200/25 µg OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		FF 100 µg OD		FF 200 µg OD		VI 25 µg OD		FF/VI 100/25 µg OD		FF/VI 200/25 µg OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/205 (4.9%)		6/204 (2.9%)		10/203 (4.9%)		16/203 (7.9%)		12/204 (5.9%)		15/205 (7.3%)
Blood and lymphatic system disorders
Leukocytosis	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Cardiac disorders
Myocardial infarction	1/205 (0.5%)		1/204 (0.5%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		1/205 (0.5%)
Acute myocardial infarction	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Atrial fibrillation	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Atrioventricular block first degree	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Bradycardia	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Cardiac failure chronic	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Cardiac failure congestive	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Myocardial ischaemia	1/205 (0.5%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Supraventricular extrasystoles	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Ear and labyrinth disorders
Vertigo	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Gastrointestinal disorders
Abdominal hernia	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Enteritis	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Hiatus hernia	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Inguinal hernia	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Oesophagitis	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Pancreatitis	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Peritonitis	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Rectal haemorrhage	1/205 (0.5%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
General disorders
Chest discomfort	1/205 (0.5%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Device occlusion	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Immune system disorders
Anaphylactic reaction	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Infections and infestations
Pneumonia	0/205 (0%)		0/204 (0%)		2/203 (1%)		2/203 (1%)		0/204 (0%)		3/205 (1.5%)
Infective exacerbation of chronic obstructive airway disease	1/205 (0.5%)		0/204 (0%)		1/203 (0.5%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Appendicitis	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		1/205 (0.5%)
Sepsis	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Injury, poisoning and procedural complications
Accidental poisoning	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Fibula fracture	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Incisional hernia	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Joint dislocation	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Subdural haematoma	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Tibia fracture	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Metabolism and nutrition disorders
Hyperglycaemia	0/205 (0%)		0/204 (0%)		1/203 (0.5%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Metabolic disorder	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Type 2 diabetes mellitus	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Musculoskeletal and connective tissue disorders
Osteoporosis	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Spinal osteoarthritis	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Gastric cancer	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Oesophageal carcinoma	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Prostate cancer	0/205 (0%)		1/204 (0.5%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Nervous system disorders
Syncope	0/205 (0%)		0/204 (0%)		2/203 (1%)		0/203 (0%)		0/204 (0%)		0/205 (0%)
Cerebral infarction	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Cerebrovascular accident	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Thrombotic stroke	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		1/204 (0.5%)		0/205 (0%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	5/205 (2.4%)		0/204 (0%)		2/203 (1%)		5/203 (2.5%)		5/204 (2.5%)		5/205 (2.4%)
Pneumothorax	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		1/205 (0.5%)
Bronchiectasis	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Pleural effusion	0/205 (0%)		0/204 (0%)		0/203 (0%)		0/203 (0%)		0/204 (0%)		1/205 (0.5%)
Vascular disorders
Venous insufficiency	0/205 (0%)		0/204 (0%)		0/203 (0%)		1/203 (0.5%)		0/204 (0%)		0/205 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		FF 100 µg OD		FF 200 µg OD		VI 25 µg OD		FF/VI 100/25 µg OD		FF/VI 200/25 µg OD
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	39/205 (19%)		32/204 (15.7%)		46/203 (22.7%)		43/203 (21.2%)		36/204 (17.6%)		40/205 (19.5%)
Infections and infestations
Nasopharyngitis	17/205 (8.3%)		14/204 (6.9%)		20/203 (9.9%)		19/203 (9.4%)		13/204 (6.4%)		13/205 (6.3%)
Upper respiratory tract infection	5/205 (2.4%)		3/204 (1.5%)		5/203 (2.5%)		9/203 (4.4%)		8/204 (3.9%)		7/205 (3.4%)
Oral candidiasis	2/205 (1%)		5/204 (2.5%)		5/203 (2.5%)		2/203 (1%)		8/204 (3.9%)		4/205 (2%)
Oropharyngeal candidiasis	3/205 (1.5%)		0/204 (0%)		7/203 (3.4%)		1/203 (0.5%)		3/204 (1.5%)		4/205 (2%)
Nervous system disorders
Headache	15/205 (7.3%)		13/204 (6.4%)		11/203 (5.4%)		20/203 (9.9%)		11/204 (5.4%)		15/205 (7.3%)
Vascular disorders
Hypertension	3/205 (1.5%)		3/204 (1.5%)		7/203 (3.4%)		0/203 (0%)		3/204 (1.5%)		1/205 (0.5%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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.