Trial Outcomes & Findings for Fluticasone Furoate/GW642444 Inhalation Powder Long-Term Safety Study (NCT NCT01018186)

NCT ID: NCT01018186

Last Updated: 2018-02-15

Results Overview

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 503 participants
• Primary outcome timeframe: From the start of study medication until Visit 11 (Week 52)/Early Withdrawal
• Results posted on: 2018-02-15

Participant Flow

Participants were randomized in a 2:2:1 ratio to Fluticasone Furoate/GW642444 Inhalation Powder (two strengths: 200/25 micrograms (µg) once daily and 100/25 µg once daily) and fluticasone propionate 500 µg twice daily, respectively.

Participants meeting all inclusion criteria and none of the exclusion criteria during the screening visit entered a 2-week Run-in Period for completion of Baseline safety evaluations and to obtain Baseline measures of asthma status. At Visit 2, participants were randomized to a 52-week Double-blind Treatment Period.

Participant milestones

Measure	Current Asthma Therapy at a Fixed Dose Participants were instructed to continue using an approved fixed dose of an inhaled corticosteroid (ICS) with or without an additional controller medication (i.e., long-acting beta-agonist, leukotriene modifier, etc.) for 2 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Run-in Period.	FF/VI 100/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
2-week Run-in Period STARTED	617	0	0	0
2-week Run-in Period COMPLETED	503	0	0	0
2-week Run-in Period NOT COMPLETED	114	0	0	0
52-week Double-blind Treatment Period STARTED	0	201	202	100
52-week Double-blind Treatment Period COMPLETED	0	161	161	71
52-week Double-blind Treatment Period NOT COMPLETED	0	40	41	29

Reasons for withdrawal

Measure	Current Asthma Therapy at a Fixed Dose Participants were instructed to continue using an approved fixed dose of an inhaled corticosteroid (ICS) with or without an additional controller medication (i.e., long-acting beta-agonist, leukotriene modifier, etc.) for 2 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Run-in Period.	FF/VI 100/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
2-week Run-in Period Protocol Violation	1	0	0	0
2-week Run-in Period Lost to Follow-up	2	0	0	0
2-week Run-in Period Physician Decision	3	0	0	0
2-week Run-in Period Withdrawal by Subject	11	0	0	0
2-week Run-in Period Did Not Meet Continuation Criteria	97	0	0	0
52-week Double-blind Treatment Period Adverse Event	0	5	3	6
52-week Double-blind Treatment Period Lack of Efficacy	0	1	4	1
52-week Double-blind Treatment Period Protocol Violation	0	8	8	2
52-week Double-blind Treatment Period Protocol-defined Stopping Criteria	0	14	16	4
52-week Double-blind Treatment Period Lost to Follow-up	0	1	3	4
52-week Double-blind Treatment Period Physician Decision	0	1	0	3
52-week Double-blind Treatment Period Withdrawal by Subject	0	10	7	9

Baseline Characteristics

Fluticasone Furoate/GW642444 Inhalation Powder Long-Term Safety Study

Baseline characteristics by cohort

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	Total n=503 Participants Total of all reporting groups
Age, Continuous	39.7 Years STANDARD_DEVIATION 15.85 • n=5 Participants	38.5 Years STANDARD_DEVIATION 15.64 • n=7 Participants	38.6 Years STANDARD_DEVIATION 15.97 • n=5 Participants	39.0 Years STANDARD_DEVIATION 15.77 • n=4 Participants
Sex: Female, Male Female	130 Participants n=5 Participants	124 Participants n=7 Participants	62 Participants n=5 Participants	316 Participants n=4 Participants
Sex: Female, Male Male	71 Participants n=5 Participants	78 Participants n=7 Participants	38 Participants n=5 Participants	187 Participants n=4 Participants
Race/Ethnicity, Customized African American/African Heritage	15 participants n=5 Participants	17 participants n=7 Participants	6 participants n=5 Participants	38 participants n=4 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	50 participants n=5 Participants	51 participants n=7 Participants	24 participants n=5 Participants	125 participants n=4 Participants
Race/Ethnicity, Customized Asian - Mixed Race	0 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	1 participants n=4 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	4 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	5 participants n=4 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	129 participants n=5 Participants	132 participants n=7 Participants	68 participants n=5 Participants	329 participants n=4 Participants
Race/Ethnicity, Customized White - Mixed Race	2 participants n=5 Participants	1 participants n=7 Participants	0 participants n=5 Participants	3 participants n=4 Participants
Race/Ethnicity, Customized Mixed Race	1 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants

PRIMARY outcome

Timeframe: From the start of study medication until Visit 11 (Week 52)/Early Withdrawal

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect. Medical or scientific judgment should be exercised in deciding whether reporting is appropriate in other situations. Refer to the General Adverse AE/SAE module for a complete list of AEs and SAEs.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period Any AE	139 participants	134 participants	73 participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period Any SAE	3 participants	1 participants	7 participants

PRIMARY outcome

Timeframe: From the start of study medication until Visit 11 (Week 52)/Early Withdrawal

Population: ITT Population

A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets, suspension, or injection) for at least 3 days or an in-patient hospitalization or emergency department visit due to asthma that required systemic corticosteroids. Courses of corticosteroids separated by 1 week or more were treated as separate severe exacerbations.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With Severe Asthma Exacerbations During the Treatment Period	3 participants	6 participants	3 participants

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of albumin and total protein values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Albumin, Week 28, n=180, 176, 79	-0.2 Grams per liter (G/L) Standard Deviation 2.68	-0.3 Grams per liter (G/L) Standard Deviation 2.79	-0.4 Grams per liter (G/L) Standard Deviation 2.76
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Albumin, Week 52, n=157, 159, 67	-0.1 Grams per liter (G/L) Standard Deviation 2.81	-0.8 Grams per liter (G/L) Standard Deviation 2.72	-0.5 Grams per liter (G/L) Standard Deviation 2.54
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Total Protein, Week 12, n=172, 182, 87	-0.6 Grams per liter (G/L) Standard Deviation 4.13	-0.1 Grams per liter (G/L) Standard Deviation 4.50	-0.6 Grams per liter (G/L) Standard Deviation 3.96
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Total Protein, Week 28, n=180, 176, 79	-1.1 Grams per liter (G/L) Standard Deviation 3.90	-1.0 Grams per liter (G/L) Standard Deviation 4.47	-0.5 Grams per liter (G/L) Standard Deviation 4.33
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Total Protein, Week 52, n=157, 159, 67	-0.7 Grams per liter (G/L) Standard Deviation 4.53	-1.4 Grams per liter (G/L) Standard Deviation 4.60	-1.0 Grams per liter (G/L) Standard Deviation 4.38
Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal Albumin, Week 12, n=172, 182, 87	0.1 Grams per liter (G/L) Standard Deviation 2.69	0.2 Grams per liter (G/L) Standard Deviation 2.87	-0.5 Grams per liter (G/L) Standard Deviation 2.64

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of ALP, ALT, AST, CK, and GGT values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALP, Week 12, n=158, 165, 84	-3.0 International units per liter (IU/L) Standard Deviation 18.76	-2.6 International units per liter (IU/L) Standard Deviation 29.65	-4.7 International units per liter (IU/L) Standard Deviation 24.47
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALP, Week 28, n=180, 176, 79	-1.0 International units per liter (IU/L) Standard Deviation 32.68	-5.8 International units per liter (IU/L) Standard Deviation 30.56	-5.7 International units per liter (IU/L) Standard Deviation 24.33
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALP, Week 52, n=157, 157, 67	-4.0 International units per liter (IU/L) Standard Deviation 30.67	-7.2 International units per liter (IU/L) Standard Deviation 34.65	-9.3 International units per liter (IU/L) Standard Deviation 27.54
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALT, Week 12, n=172, 182, 87	-1.0 International units per liter (IU/L) Standard Deviation 10.43	-0.2 International units per liter (IU/L) Standard Deviation 13.51	-0.3 International units per liter (IU/L) Standard Deviation 12.03
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALT, Week 28, n=180, 176, 79	-1.6 International units per liter (IU/L) Standard Deviation 10.08	-0.1 International units per liter (IU/L) Standard Deviation 10.59	0.4 International units per liter (IU/L) Standard Deviation 11.96
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal ALT, Week 52, n=157, 159, 67	-1.8 International units per liter (IU/L) Standard Deviation 12.40	-1.3 International units per liter (IU/L) Standard Deviation 11.13	-0.1 International units per liter (IU/L) Standard Deviation 9.78
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal AST, Week 12, n=171, 181, 87	-0.9 International units per liter (IU/L) Standard Deviation 8.07	-0.3 International units per liter (IU/L) Standard Deviation 12.05	0.3 International units per liter (IU/L) Standard Deviation 8.69
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal AST, Week 28, n=179, 176, 79	-1.4 International units per liter (IU/L) Standard Deviation 8.42	-0.9 International units per liter (IU/L) Standard Deviation 11.60	1.3 International units per liter (IU/L) Standard Deviation 10.65
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal AST, Week 52, n=156, 158, 67	-1.8 International units per liter (IU/L) Standard Deviation 8.78	-1.9 International units per liter (IU/L) Standard Deviation 11.21	-0.2 International units per liter (IU/L) Standard Deviation 9.22
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal GGT, Week 12, n=172, 182, 87	0.9 International units per liter (IU/L) Standard Deviation 12.90	-0.1 International units per liter (IU/L) Standard Deviation 18.23	-1.7 International units per liter (IU/L) Standard Deviation 12.12
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal GGT, Week 28, n=180, 176, 79	3.3 International units per liter (IU/L) Standard Deviation 33.79	-0.6 International units per liter (IU/L) Standard Deviation 17.63	-0.2 International units per liter (IU/L) Standard Deviation 11.85
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal GGT, Week 52, n=157, 159, 67	2.7 International units per liter (IU/L) Standard Deviation 40.34	-2.7 International units per liter (IU/L) Standard Deviation 15.99	-0.5 International units per liter (IU/L) Standard Deviation 13.30
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine Kinase, Week 12, n=172, 181, 87	10.8 International units per liter (IU/L) Standard Deviation 92.06	-11.5 International units per liter (IU/L) Standard Deviation 254.71	-18.3 International units per liter (IU/L) Standard Deviation 223.59
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine Kinase, Week 52, n=157, 159, 67	-0.7 International units per liter (IU/L) Standard Deviation 69.12	-16.8 International units per liter (IU/L) Standard Deviation 266.48	-27.7 International units per liter (IU/L) Standard Deviation 274.14
Change From Baseline in Alkaline Phosphatase (ALP), Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST), Creatine Kinase (CK), and Gamma Glutamyltransferase (GGT) at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine Kinase, Week 28, n=180, 176, 79	2.0 International units per liter (IU/L) Standard Deviation 68.72	-9.9 International units per liter (IU/L) Standard Deviation 247.61	15.3 International units per liter (IU/L) Standard Deviation 441.68

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of direct bilirubin, indirect bilirubin, total bilirubin, and creatinine values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Direct bilirubin, Week 28, n=180, 176, 79	-0.3 Micromoles per liter (µmol/L) Standard Deviation 0.97	-0.2 Micromoles per liter (µmol/L) Standard Deviation 1.01	-0.1 Micromoles per liter (µmol/L) Standard Deviation 0.94
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Total Bilirubin, Week 12, n=172, 182, 87	-1.7 Micromoles per liter (µmol/L) Standard Deviation 3.62	-1.1 Micromoles per liter (µmol/L) Standard Deviation 3.46	-0.8 Micromoles per liter (µmol/L) Standard Deviation 3.44
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Total Bilirubin, Week 28, n=180, 175, 79	-1.6 Micromoles per liter (µmol/L) Standard Deviation 3.61	-1.2 Micromoles per liter (µmol/L) Standard Deviation 3.55	-0.5 Micromoles per liter (µmol/L) Standard Deviation 3.46
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Total Bilirubin, Week 52, n=157, 159, 67	-2.4 Micromoles per liter (µmol/L) Standard Deviation 3.58	-2.0 Micromoles per liter (µmol/L) Standard Deviation 2.93	-1.0 Micromoles per liter (µmol/L) Standard Deviation 3.14
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine, Week 12, n=172, 181, 87	3.00 Micromoles per liter (µmol/L) Standard Deviation 10.214	3.18 Micromoles per liter (µmol/L) Standard Deviation 7.983	3.99 Micromoles per liter (µmol/L) Standard Deviation 8.056
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine, Week 28, n=180, 176, 79	7.03 Micromoles per liter (µmol/L) Standard Deviation 19.264	5.10 Micromoles per liter (µmol/L) Standard Deviation 10.316	17.43 Micromoles per liter (µmol/L) Standard Deviation 92.175
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Creatinine, Week 52, n=157, 159, 67	2.74 Micromoles per liter (µmol/L) Standard Deviation 9.450	3.14 Micromoles per liter (µmol/L) Standard Deviation 11.310	3.32 Micromoles per liter (µmol/L) Standard Deviation 9.982
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Direct bilirubin, Week 12, n=172, 182, 87	-0.3 Micromoles per liter (µmol/L) Standard Deviation 0.99	-0.3 Micromoles per liter (µmol/L) Standard Deviation 0.98	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.93
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Direct bilirubin, Week 52, n=157, 159, 67	-0.4 Micromoles per liter (µmol/L) Standard Deviation 0.99	-0.4 Micromoles per liter (µmol/L) Standard Deviation 1.00	-0.2 Micromoles per liter (µmol/L) Standard Deviation 0.90
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Indirect bilirubin, Week 12, n=172, 182, 87	-1.4 Micromoles per liter (µmol/L) Standard Deviation 3.11	-0.8 Micromoles per liter (µmol/L) Standard Deviation 2.86	-0.6 Micromoles per liter (µmol/L) Standard Deviation 3.04
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Indirect bilirubin, Week 28, n=180, 175, 79	-1.3 Micromoles per liter (µmol/L) Standard Deviation 3.09	-0.9 Micromoles per liter (µmol/L) Standard Deviation 2.87	-0.4 Micromoles per liter (µmol/L) Standard Deviation 3.14
Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal Indirect bilirubin, Week 52, n=157, 159, 67	-2.0 Micromoles per liter (µmol/L) Standard Deviation 3.08	-1.6 Micromoles per liter (µmol/L) Standard Deviation 2.51	-0.8 Micromoles per liter (µmol/L) Standard Deviation 2.68

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of chloride, carbon dioxide (CO2) content/bicarbonate, glucose, potassium, sodium, and urea/BUN values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Chloride, Week 12, n=172, 182, 87	-0.7 Millimoles per liter (mmol/L) Standard Deviation 3.43	-0.4 Millimoles per liter (mmol/L) Standard Deviation 3.50	0.1 Millimoles per liter (mmol/L) Standard Deviation 2.28
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Chloride, Week 28, n=180, 176, 79	-0.1 Millimoles per liter (mmol/L) Standard Deviation 2.50	0.2 Millimoles per liter (mmol/L) Standard Deviation 2.73	-0.1 Millimoles per liter (mmol/L) Standard Deviation 2.54
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Chloride, Week 52, n=157, 159, 67	-0.5 Millimoles per liter (mmol/L) Standard Deviation 2.51	0.0 Millimoles per liter (mmol/L) Standard Deviation 2.67	-0.3 Millimoles per liter (mmol/L) Standard Deviation 2.31
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal CO2 content/bicarbonate, Week 12, n=171, 181, 87	-0.7 Millimoles per liter (mmol/L) Standard Deviation 3.13	-0.8 Millimoles per liter (mmol/L) Standard Deviation 2.91	-0.2 Millimoles per liter (mmol/L) Standard Deviation 2.72
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal CO2 content/bicarbonate, Week 28, n=179, 176, 79	0.3 Millimoles per liter (mmol/L) Standard Deviation 2.90	0.1 Millimoles per liter (mmol/L) Standard Deviation 2.61	0.9 Millimoles per liter (mmol/L) Standard Deviation 2.60
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal CO2 content/bicarbonate, Week 52, n=156, 158, 67	-0.1 Millimoles per liter (mmol/L) Standard Deviation 2.53	0.1 Millimoles per liter (mmol/L) Standard Deviation 2.51	0.5 Millimoles per liter (mmol/L) Standard Deviation 2.55
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Glucose, Week 12, n=172, 181, 87	0.33 Millimoles per liter (mmol/L) Standard Deviation 1.873	0.17 Millimoles per liter (mmol/L) Standard Deviation 2.085	0.10 Millimoles per liter (mmol/L) Standard Deviation 1.233
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Glucose, Week 28, n=180, 175, 79	0.21 Millimoles per liter (mmol/L) Standard Deviation 1.547	0.16 Millimoles per liter (mmol/L) Standard Deviation 1.556	0.02 Millimoles per liter (mmol/L) Standard Deviation 1.442
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Glucose, Week 52, n=157, 159, 67	0.45 Millimoles per liter (mmol/L) Standard Deviation 1.839	0.11 Millimoles per liter (mmol/L) Standard Deviation 1.426	-0.20 Millimoles per liter (mmol/L) Standard Deviation 1.191
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Potassium, Week 12, n=157, 165, 84	-0.09 Millimoles per liter (mmol/L) Standard Deviation 0.572	0.00 Millimoles per liter (mmol/L) Standard Deviation 0.721	-0.03 Millimoles per liter (mmol/L) Standard Deviation 0.606
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Potassium, Week 28, n=179, 176, 79	-0.12 Millimoles per liter (mmol/L) Standard Deviation 0.467	-0.15 Millimoles per liter (mmol/L) Standard Deviation 0.449	0.02 Millimoles per liter (mmol/L) Standard Deviation 0.617
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Potassium, Week 52, n=156, 156, 67	-0.18 Millimoles per liter (mmol/L) Standard Deviation 0.461	-0.12 Millimoles per liter (mmol/L) Standard Deviation 0.535	-0.10 Millimoles per liter (mmol/L) Standard Deviation 0.446
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Sodium, Week 12, n=172, 182, 87	-0.1 Millimoles per liter (mmol/L) Standard Deviation 2.47	0.2 Millimoles per liter (mmol/L) Standard Deviation 2.61	-0.0 Millimoles per liter (mmol/L) Standard Deviation 2.24
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Sodium, Week 28, n=180, 176, 79	0.0 Millimoles per liter (mmol/L) Standard Deviation 2.46	0.2 Millimoles per liter (mmol/L) Standard Deviation 2.65	0.3 Millimoles per liter (mmol/L) Standard Deviation 2.74
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Sodium, Week 52, n=157, 159, 67	-0.2 Millimoles per liter (mmol/L) Standard Deviation 2.57	0.1 Millimoles per liter (mmol/L) Standard Deviation 2.52	0.0 Millimoles per liter (mmol/L) Standard Deviation 2.80
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Urea/BUN, Week 12, n=172, 182, 87	0.24 Millimoles per liter (mmol/L) Standard Deviation 1.299	0.36 Millimoles per liter (mmol/L) Standard Deviation 1.237	0.02 Millimoles per liter (mmol/L) Standard Deviation 1.757
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Urea/BUN, Week 28, n=180, 176, 79	0.16 Millimoles per liter (mmol/L) Standard Deviation 1.460	0.14 Millimoles per liter (mmol/L) Standard Deviation 1.124	0.41 Millimoles per liter (mmol/L) Standard Deviation 2.676
Change From Baseline in Chloride, Carbon Dioxide Content/Bicarbonate, Glucose, Potassium, Sodium, and Urea/Blood Urea Nitrogen (BUN) at Week 12, Week 28, and Week 52/Early Withdrawal Urea/BUN, Week 52, n=157, 159, 67	0.15 Millimoles per liter (mmol/L) Standard Deviation 1.244	0.13 Millimoles per liter (mmol/L) Standard Deviation 1.479	-0.04 Millimoles per liter (mmol/L) Standard Deviation 1.900

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of the percentage of basophils, eosinophils, hematocrit, lymphocytes, monocytes, and segmented neutrophils in the blood at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=101 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Basophils, Week 12, n=171, 170, 86	-0.01 Percentage Standard Deviation 0.330	-0.06 Percentage Standard Deviation 0.331	-0.08 Percentage Standard Deviation 0.320
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Basophils, Week 28, n=169, 169, 77	-0.01 Percentage Standard Deviation 0.319	0.00 Percentage Standard Deviation 0.338	-0.06 Percentage Standard Deviation 0.310
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Basophils, Week 52, n=155, 155, 71	0.02 Percentage Standard Deviation 0.314	-0.03 Percentage Standard Deviation 0.279	-0.07 Percentage Standard Deviation 0.319
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophils, Week 12, n=171, 170, 86	-0.35 Percentage Standard Deviation 4.048	-0.88 Percentage Standard Deviation 3.825	-1.23 Percentage Standard Deviation 3.391
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophils, Week 28, n=169, 169, 77	-0.97 Percentage Standard Deviation 3.991	-1.34 Percentage Standard Deviation 3.774	-1.63 Percentage Standard Deviation 3.574
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophils, Week 52, n=155, 155, 71	-0.84 Percentage Standard Deviation 4.096	-0.90 Percentage Standard Deviation 3.946	-1.19 Percentage Standard Deviation 3.611
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Lymphocytes, Week 12, n=171, 170, 86	-0.57 Percentage Standard Deviation 9.280	-0.91 Percentage Standard Deviation 8.414	-1.72 Percentage Standard Deviation 8.449
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Lymphocytes, Week 28, n=169, 169, 77	-1.11 Percentage Standard Deviation 8.816	-1.31 Percentage Standard Deviation 10.200	-1.66 Percentage Standard Deviation 11.054
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Lymphocytes, Week 52, n=155, 155, 71	1.34 Percentage Standard Deviation 9.389	-0.03 Percentage Standard Deviation 10.137	-0.97 Percentage Standard Deviation 8.532
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Monocytes, Week 12, n=171, 170, 86	-0.60 Percentage Standard Deviation 2.692	-0.47 Percentage Standard Deviation 2.500	-0.86 Percentage Standard Deviation 3.147
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Monocytes, Week 28, n=169, 169, 77	-0.66 Percentage Standard Deviation 2.594	-0.53 Percentage Standard Deviation 2.706	-0.84 Percentage Standard Deviation 3.063
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Monocytes, Week 52, n=155, 155, 71	-0.19 Percentage Standard Deviation 2.439	0.31 Percentage Standard Deviation 2.598	-0.30 Percentage Standard Deviation 2.337
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Segmented neutrophils, Week 12, n=171, 170, 86	1.54 Percentage Standard Deviation 10.883	2.32 Percentage Standard Deviation 9.635	3.89 Percentage Standard Deviation 11.397
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Segmented neutrophils, Week 28, n=169, 169, 77	2.71 Percentage Standard Deviation 10.221	3.18 Percentage Standard Deviation 12.008	4.19 Percentage Standard Deviation 13.745
Change From Baseline in the Percentage of Basophils, Eosinophils, Hematocrit, Lymphocytes, Monocytes, and Segmented Neutrophils in the Blood at Week 12, Week 28, and Week 52/Early Withdrawal Segmented neutrophils, Week 52, n=155, 155, 71	-0.33 Percentage Standard Deviation 10.687	0.66 Percentage Standard Deviation 11.768	2.54 Percentage Standard Deviation 10.112

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed for different parameters, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected to determine the eosinophil count, total ANC, platelet count, and WBC count at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Platelet Count, Week 12, n=167, 159, 78	-1.3 10^9 cells per liter (GI/L) Standard Deviation 39.44	1.5 10^9 cells per liter (GI/L) Standard Deviation 68.10	1.5 10^9 cells per liter (GI/L) Standard Deviation 43.26
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophil count, Week 12, n=171, 170, 86	-0.010 10^9 cells per liter (GI/L) Standard Deviation 0.3226	-0.057 10^9 cells per liter (GI/L) Standard Deviation 0.3841	-0.073 10^9 cells per liter (GI/L) Standard Deviation 0.2220
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophil count, Week 28, n=169, 169, 77	-0.039 10^9 cells per liter (GI/L) Standard Deviation 0.3310	-0.083 10^9 cells per liter (GI/L) Standard Deviation 0.3698	-0.083 10^9 cells per liter (GI/L) Standard Deviation 0.2363
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Eosinophil count, Week 52, n=155, 155, 71	-0.023 10^9 cells per liter (GI/L) Standard Deviation 0.3273	-0.037 10^9 cells per liter (GI/L) Standard Deviation 0.3171	-0.044 10^9 cells per liter (GI/L) Standard Deviation 0.2539
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Total ANC, Week 12, n=171, 170, 86	0.392 10^9 cells per liter (GI/L) Standard Deviation 1.6161	0.469 10^9 cells per liter (GI/L) Standard Deviation 1.6904	0.493 10^9 cells per liter (GI/L) Standard Deviation 1.7488
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Total ANC, Week 52, n=136, 136, 60	0.524 10^9 cells per liter (GI/L) Standard Deviation 1.4589	0.612 10^9 cells per liter (GI/L) Standard Deviation 1.9100	0.748 10^9 cells per liter (GI/L) Standard Deviation 1.7946
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Platelet Count, Week 52, n=147, 151, 68	1.8 10^9 cells per liter (GI/L) Standard Deviation 43.80	4.6 10^9 cells per liter (GI/L) Standard Deviation 38.49	16.4 10^9 cells per liter (GI/L) Standard Deviation 50.99
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal WBC Count, Week 12, n=173, 170, 86	0.51 10^9 cells per liter (GI/L) Standard Deviation 1.744	0.50 10^9 cells per liter (GI/L) Standard Deviation 2.007	0.39 10^9 cells per liter (GI/L) Standard Deviation 1.906
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal WBC Count, Week 28, n=170, 169, 77	0.74 10^9 cells per liter (GI/L) Standard Deviation 1.758	0.74 10^9 cells per liter (GI/L) Standard Deviation 2.103	0.79 10^9 cells per liter (GI/L) Standard Deviation 2.028
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal WBC Count, Week 52, n=156, 156, 71	0.91 10^9 cells per liter (GI/L) Standard Deviation 1.639	0.83 10^9 cells per liter (GI/L) Standard Deviation 2.046	1.01 10^9 cells per liter (GI/L) Standard Deviation 1.909
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Total ANC, Week 28, n=169, 169, 77	0.632 10^9 cells per liter (GI/L) Standard Deviation 1.5922	0.679 10^9 cells per liter (GI/L) Standard Deviation 2.0157	0.750 10^9 cells per liter (GI/L) Standard Deviation 2.0130
Change From Baseline in Eosinophil Count, Total Absolute Neutrophil Count (ANC), Platelet Count, and White Blood Cell (WBC) Count at Week 12, Week 28, and Week 52/Early Withdrawal Platelet Count, Week 28, n=164, 165, 74	1.0 10^9 cells per liter (GI/L) Standard Deviation 44.49	3.5 10^9 cells per liter (GI/L) Standard Deviation 35.06	12.4 10^9 cells per liter (GI/L) Standard Deviation 43.59

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of hematocrit values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Hematocrit at Week 12, Week 28, and Week 52/Early Withdrawal Week 12, n=176, 172, 86	-0.0073 Proportion of 1.0 Standard Deviation 0.02307	-0.0013 Proportion of 1.0 Standard Deviation 0.02654	-0.0025 Proportion of 1.0 Standard Deviation 0.02318
Change From Baseline in Hematocrit at Week 12, Week 28, and Week 52/Early Withdrawal Week 28, n=172, 170, 77	-0.0017 Proportion of 1.0 Standard Deviation 0.02213	-0.0005 Proportion of 1.0 Standard Deviation 0.02464	-0.0028 Proportion of 1.0 Standard Deviation 0.02168
Change From Baseline in Hematocrit at Week 12, Week 28, and Week 52/Early Withdrawal Week 52, n=157, 159, 72	-0.0027 Proportion of 1.0 Standard Deviation 0.02906	-0.0021 Proportion of 1.0 Standard Deviation 0.02467	-0.0045 Proportion of 1.0 Standard Deviation 0.02495

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Blood samples were collected for the measurement of hemoglobin values at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the most recent recorded value at Screening or prior to Day 1. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Hemoglobin at Week 12, Week 28, and Week 52/Early Withdrawal Week 12, n=176, 172, 86	-3.4 Grams per liter (g/L) Standard Deviation 7.48	-1.8 Grams per liter (g/L) Standard Deviation 8.25	-2.0 Grams per liter (g/L) Standard Deviation 7.67
Change From Baseline in Hemoglobin at Week 12, Week 28, and Week 52/Early Withdrawal Week 28, n=172, 170, 77	-2.1 Grams per liter (g/L) Standard Deviation 7.64	-2.2 Grams per liter (g/L) Standard Deviation 8.11	-2.4 Grams per liter (g/L) Standard Deviation 7.72
Change From Baseline in Hemoglobin at Week 12, Week 28, and Week 52/Early Withdrawal Week 52, n=157, 159, 72	-2.6 Grams per liter (g/L) Standard Deviation 10.26	-2.9 Grams per liter (g/L) Standard Deviation 7.47	-3.0 Grams per liter (g/L) Standard Deviation 8.77

PRIMARY outcome

Timeframe: Baseline; Week 12, Week 28, and Week 52/Early Withdrawal

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

A 24-hour urine sample was collected for the measurement of 24-hour urinary cortisol excretion (UCE) at the following scheduled time points: Baseline, Week 12, Week 28, and Week 52/Early Withdrawal. Any visit post-baseline (AVPB) value was derived using laboratory assessments performed at scheduled, unscheduled, and Early Withdrawal visits. Participants who had a shift from Baseline in their post-Baseline UCE values relative to the normal range, are presented in the "To high and To low" categories. Participants whose post-Baseline UCE values were unchanged (e.g., High to High) or whose value became normal, are presented in the "To normal or no change" category. The normal range for UCE is defined as: 11 to 138 nanomoles per 24 hours (nmol/24 hr) for participants >=18 years of age, 8.3 to 151.7 nmol/24 hr for participants 14 to 17 years of age, and 2.8 to 124.2 nmol/24 hr for participants 12 and 13 years of age.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 12: To high, n=139, 140, 78	6 participants Interval 4.5 to 160.6	7 participants Interval 5.9 to 491.8	2 participants Interval 5.3 to 780.5
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 12: To low, n=139, 140, 78	2 participants Interval 4.0 to 602.3	5 participants Interval 10.4 to 549.6	9 participants Interval 3.4 to 396.4
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 28: To high, n=135, 131, 59	8 participants	8 participants	3 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 28: To normal or no change, n=135, 131, 59	123 participants	120 participants	47 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 28: To low, n=135, 131, 59	4 participants	3 participants	9 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 52: To high, n=134, 140, 65	10 participants	7 participants	4 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 52: To normal or no change , n=134, 140, 65	119 participants	131 participants	57 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 52: To low, n=134, 140, 65	5 participants	2 participants	4 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion AVBP: To high, n=156, 156, 83	25 participants	21 participants	8 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion AVBP: To normal or no change, n=156, 156, 83	119 participants	126 participants	58 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion AVBP: To low, n=156, 156, 83	12 participants	9 participants	17 participants
Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion Week 12: To normal or no change, n=139, 140, 78	131 participants Interval 5.7 to 547.4	128 participants Interval 6.1 to 482.5	67 participants Interval 3.8 to 667.5

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Urinary cortisol (UC) Population: participants in the ITT Population whose urine samples did not have confounding factors that affected the interpretation of results. These participants were determined prior to breaking the blind. Only those participants available at the specified time point were analyzed.

A 24-hour urine sample was collected, and the least square geometric mean (LSGM) for 24-hour urinary cortisol excretion (UCE) was calculated at Baseline and at Week 12. The ratio of the Week 12 LSGM to the Baseline LSGM was calculated as the value at Week 12 divided by the value at Baseline. Analysis was performed using analysis of covariance (ANCOVA) with covariates of region, sex, age, treatment, and the log of the Baseline values.

Outcome measures

Measure	FF/VI 100/25 µg OD n=129 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=129 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=71 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Ratio of 24-hour Urinary Cortisol Excretion at Week 12 to Baseline	1.03 Ratio of LSGM of UCE to Baseline	0.93 Ratio of LSGM of UCE to Baseline	0.61 Ratio of LSGM of UCE to Baseline

PRIMARY outcome

Timeframe: Baseline and Week 28

Population: UC Population. Only those participants available at the specified time point were analyzed.

A 24-hour urine sample was collected, and the LSGM for 24-hour UCE was calculated at Baseline and at Week 28. The ratio of the Week 28 LSGM to the Baseline LSGM was calculated as the value at Week 28 divided by the value at Baseline. Analysis was performed using ANCOVA with covariates of region, sex, age, treatment, and the log of the Baseline values.

Outcome measures

Measure	FF/VI 100/25 µg OD n=128 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=121 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=56 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Ratio of 24-hour Urinary Cortisol Excretion at Week 28 to Baseline	1.05 Ratio of LSGM of UCE to Baseline	0.91 Ratio of LSGM of UCE to Baseline	0.64 Ratio of LSGM of UCE to Baseline

PRIMARY outcome

Timeframe: Baseline and Week 52

Population: UC Population. Only those participants available at the specified time point were analyzed.

A 24-hour urine sample was collected, and the LSGM for 24-hour UCE was calculated at Baseline and at Week 52. The ratio of the Week 52 LSGM to the Baseline LSGM was calculated as the value at Week 52 divided by the value at Baseline. Analysis was performed using ANCOVA with covariates of region, sex, age, treatment, and the log of the Baseline values.

Outcome measures

Measure	FF/VI 100/25 µg OD n=125 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=127 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=60 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Ratio of 24-hour Urinary Cortisol Excretion at Week 52 to Baseline	1.00 Ratio of LSGM of UCE to Baseline	1.04 Ratio of LSGM of UCE to Baseline	0.95 Ratio of LSGM of UCE to Baseline

PRIMARY outcome

Timeframe: From Baseline until Visit 11/Early Withdrawal (52 weeks)

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

A detailed oropharyngeal examination was done at all clinic visits for visual/clinical evidence of oral candidiasis over the entire Treatment Period (worst case any time post-Baseline). For participants with visual/clinical evidence of candidiasis during the Treatment Phase of the study, a culture swab was taken and analyzed for infection.

Outcome measures

Measure	FF/VI 100/25 µg OD n=199 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=200 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline Evidence of oral candidiasis	15 participants	14 participants	5 participants
Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline Positive culture swab	13 participants	11 participants	3 participants
Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline Negative culture swab	1 participants	2 participants	2 participants
Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline No swab result available	1 participants	1 participants	0 participants

PRIMARY outcome

Timeframe: From Baseline until Visit 11/Early Withdrawal (52 weeks)

Population: ITT Population

SBP and DBP were measured at the following scheduled time points: Screening, Day 1, Week 2, Week 4, Week 8, Week 12, Week 20, Week 28, Week 36, Week 44, and Week 52/Early Withdrawal. Baseline is defined as the Visit 1 (screening) value. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline. Maximum and minimum change from Baseline for any post-Baseline visit was derived using all scheduled, unscheduled, and Early Withdrawal visits.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Maximum Change From Baseline in Systolic Blood Pressure (SBP) and Minimum Change From Baseline in Diastolic Blood Pressure (DBP) Maximum post-Baseline change in SBP	10.2 Millimeters of mercury (mmHg) Standard Deviation 11.05	10.0 Millimeters of mercury (mmHg) Standard Deviation 10.17	11.3 Millimeters of mercury (mmHg) Standard Deviation 11.09
Maximum Change From Baseline in Systolic Blood Pressure (SBP) and Minimum Change From Baseline in Diastolic Blood Pressure (DBP) Minimum post-Baseline change in DBP	-8.9 Millimeters of mercury (mmHg) Standard Deviation 7.70	-9.0 Millimeters of mercury (mmHg) Standard Deviation 8.44	-8.0 Millimeters of mercury (mmHg) Standard Deviation 7.76

PRIMARY outcome

Timeframe: From Baseline until Visit 11/Early Withdrawal (52 weeks)

Population: ITT Population

Pulse rate was measured at the following scheduled time points: Screening, Day 1, Week 2, Week 4, Week 8, Week 12, Week 20,Week 28, Week 36, Week 44, and Week 52/Early Withdrawal. Baseline is defined as the Visit 1 (screening) value. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline. Maximum change from Baseline for any post-Baseline visit was derived using all scheduled, unscheduled, and Early Withdrawal visits.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Maximum Change From Baseline in Pulse Rate	10.5 Beats per minute Standard Deviation 9.30	10.0 Beats per minute Standard Deviation 10.05	7.5 Beats per minute Standard Deviation 8.29

PRIMARY outcome

Timeframe: Baseline; Week 28, and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

P is defined as the opacification at the back of the lens adjacent to the capsule (or bag) in which the lens sits. An event of P is defined as an increase of >=0.3 from Baseline in LOCS III grade for P in either eye at any time post-Baseline. Per LOC III, P ranges from 0.1 (clear or colorless) to 5.9 (very opaque). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, <0.3, Week 28, n=179, 177, 80	174 participants	175 participants	79 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, >=0.3 and <0.5, Week 28, n=179, 177, 80	5 participants	2 participants	1 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, >=0.5, Week 28, n=179, 177, 80	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, <0.3, Week 28, n=179, 177, 80	175 participants	175 participants	80 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, >=0.3 and <0.5, Week 28, n=179, 177, 80	4 participants	2 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, >=0.5, Week 28, n=179, 177, 80	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, >=0.3 and <0.5, Week 52, n=167, 166, 72	2 participants	1 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, >=0.5, Week 52, n=167, 166, 72	2 participants	1 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, <0.3, Week 52, n=167, 166, 72	163 participants	164 participants	72 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, >=0.5, Week 52, n=167, 166, 72	1 participants	1 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Left eye, <0.3, Week 52, n=167, 166, 72	163 participants	164 participants	72 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Posterior Subcapsular Opacity (P) at Week 28 and Week 52 Right eye, >=0.3 and <0.5, Week 52, n=167, 166, 72	3 participants	1 participants	0 participants

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Intraocular pressure (IOP) is the fluid pressure inside the eye. IOP was measured twice for each eye at Baseline, Week 28, and Week 52 using Goldmann Applanation tonometry. The second IOP reading was used for analysis. The number of participants with a change from Baseline in IOP of <0 mmHg, >=0 to <4 mmHg, >=4 to <7 mmHg, >=7 to <11 mmHg, and >=11 mmHg are presented. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, <0 mmHg, Week 28, n=179, 177, 80	71 participants	78 participants	32 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=11 mmHg, Week 28, n=179, 177, 80	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=0 to <4 mmHg, Week 28, n=179, 177, 80	101 participants	110 participants	38 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=0 to <4 mmHg, Week 28, n=179, 177, 80	101 participants	92 participants	46 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=4 to <7 mmHg, Week 28, n=179, 177, 80	7 participants	6 participants	2 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=7 to <11 mmHg, Week 28, n=179, 177, 80	0 participants	1 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, <0 mmHg, Week 28, n=179, 177, 80	73 participants	61 participants	38 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=4 to <7 mmHg, Week 28, n=179, 177, 80	5 participants	5 participants	4 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=7 to <11 mmHg,Week 28, n=179, 177, 80	0 participants	1 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=11 mmHg, Week 28, n=179, 177, 80	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, <0 mmHg, Week 52, n=167, 166, 72	66 participants	69 participants	33 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=0 to <4 mmHg, Week 52, n=167, 166, 72	88 participants	83 participants	36 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=4 to <7 mmHg, Week 52, n=167, 166, 72	11 participants	14 participants	3 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=7 to <11 mmHg, Week 52, n=167, 166, 72	2 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Left eye, >=11 mmHg, Week 52, n=167, 166, 72	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, <0 mmHg, Week 52, n=167, 166, 72	63 participants	61 participants	32 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=0 to <4 mmHg, Week 52, n=167, 166, 72	94 participants	93 participants	40 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=4 to <7 mmHg, Week 52, n=167, 166, 72	10 participants	12 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=7 to <11 mmHg, Week 52, n=167,166, 72	0 participants	0 participants	0 participants
Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52 Right eye, >=11 mmHg, Week 52, n=167, 166, 72	0 participants	0 participants	0 participants

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Funduscopic examination was performed at Baseline, Week 28, and Week 52 to measure the horizontal cup-to-disc ratio of both eyes. The horizontal cup-to-disc ratio is the ratio of the horizontal diameter of the physiological cup to that of the horizontal diameter of the optic disc. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52 Left eye, Week 52, n=167, 166, 72	0.4 ratio Standard Deviation 5.86	0.2 ratio Standard Deviation 4.89	0.3 ratio Standard Deviation 4.77
Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52 Left eye, Week 28, n=179, 177, 80	0.5 ratio Standard Deviation 4.79	-0.2 ratio Standard Deviation 5.11	0.5 ratio Standard Deviation 4.87
Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52 Right eye, Week 28, n=179, 177, 80	0.2 ratio Standard Deviation 4.17	-0.2 ratio Standard Deviation 6.49	0.5 ratio Standard Deviation 5.10
Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52 Right eye, Week 52, n=167, 166, 72	0.1 ratio Standard Deviation 4.63	0.2 ratio Standard Deviation 5.57	0.0 ratio Standard Deviation 5.26

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

C is defined as the opacification of the cortex (outer layer) of the lens. Per LOC III, C ranges from 0.1 (clear or colorless) to 5.9 (very opaque). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, <0.3, Week 28, n=179, 177, 80	167 participants	166 participants	75 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, >=0.3 and <0.5, Week 28, n=179, 177, 80	6 participants	5 participants	4 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, >=0.5, Week 28, n=179, 177, 80	6 participants	6 participants	1 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, <0.3, Week 28, n=179, 177, 80	169 participants	172 participants	75 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, >=0.3 and <0.5, Week 28, n=179, 177, 80	5 participants	1 participants	4 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, >=0.5, Week 28, n=179, 177, 80	5 participants	4 participants	1 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, <0.3, Week 52, n=167, 166, 72	154 participants	156 participants	66 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, >=0.3 and <0.5, Week 52, n=167, 166, 72	7 participants	4 participants	3 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Left eye, >=0.5, Week 52, n=167, 166, 72	6 participants	6 participants	3 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, <0.3, Week 52, n=167, 166, 72	151 participants	158 participants	69 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, >=0.3 and <0.5, Week 52, n=167, 166, 72	11 participants	2 participants	2 participants
Number of Participants With the Indicated Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Cortical Opacity (C) at Week 28 and Week 52 Right eye, >=0.5, Week 52, n=167, 166, 72	5 participants	6 participants	1 participants

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

NC is the color of the nucleus (central layer) of the lens. Per LOC III, NC ranges from 0.1 (clear or colorless) to 6.9 (very opaque or brunescent). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52 Week 52, Left eye, n=167, 166, 72	0.02 Scores on a scale Standard Deviation 0.281	-0.2 Scores on a scale Standard Deviation 0.357	0.00 Scores on a scale Standard Deviation 0.340
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52 Week 28, Left eye, n=179, 177, 80	0.01 Scores on a scale Standard Deviation 0.282	0.00 Scores on a scale Standard Deviation 0.284	-0.02 Scores on a scale Standard Deviation 0.299
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52 Week 28, Right eye, n=179, 177, 80	0.01 Scores on a scale Standard Deviation 0.292	0.1 Scores on a scale Standard Deviation 0.292	-0.02 Scores on a scale Standard Deviation 0.294
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52 Week 52, Right eye, n=167, 166, 72	0.02 Scores on a scale Standard Deviation 0.304	0.00 Scores on a scale Standard Deviation 0.339	0.01 Scores on a scale Standard Deviation 0.336

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

NO is the opalescence of the nucleus (central layer) of the lens. Per LOC III, NO ranges from 0.1 (clear or colorless) to 6.9 (very opaque or brunescent). Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52 Week 28, Left eye, n=179, 177, 80	0.02 Scores on a scale Standard Deviation 0.236	0.03 Scores on a scale Standard Deviation 0.316	-0.02 Scores on a scale Standard Deviation 0.270
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52 Week 28, Right eye, n=179, 177, 80	0.01 Scores on a scale Standard Deviation 0.256	0.03 Scores on a scale Standard Deviation 0.303	-0.03 Scores on a scale Standard Deviation 0.272
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52 Week 52, Left eye, n=167, 166, 72	0.01 Scores on a scale Standard Deviation 0.330	0.03 Scores on a scale Standard Deviation 0.303	0.01 Scores on a scale Standard Deviation 0.369
Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52 Week 52, Right eye, n=167, 166, 72	0.00 Scores on a scale Standard Deviation 0.351	0.04 Scores on a scale Standard Deviation 0.282	0.02 Scores on a scale Standard Deviation 0.371

PRIMARY outcome

Timeframe: Baseline; Week 28 and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Visual acuity is defined as the acuteness or clearness of vision. The minimum angle of resolution (MAR) is the angle a viewed object subtends at the eye, usually stated in degrees/minutes of arc. Visual acuity was measured using Early Treatment Diabetic Retinopathy Study (ETDRS) charts in decimal numbers. The LogMAR scale is used to express the visual acuity in a linear scale as the logarithm to base 10 of the MAR. A lower score indicates better visual acuity; visual acuity decreases with an increasing score. Change from Baseline was calculated as the value at the post-Baseline time point minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52 Week 28, Left eye, n=179, 176, 80	-0.008 Scores on a scale Standard Deviation 0.0723	-0.010 Scores on a scale Standard Deviation 0.0706	-0.004 Scores on a scale Standard Deviation 0.0685
Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52 Week 28, Right eye, n=179, 176, 80	-0.003 Scores on a scale Standard Deviation 0.0739	-0.001 Scores on a scale Standard Deviation 0.0699	-0.008 Scores on a scale Standard Deviation 0.0584
Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52 Week 52, Left eye, n=167, 165, 72	-0.011 Scores on a scale Standard Deviation 0.0747	-0.012 Scores on a scale Standard Deviation 0.0739	-0.007 Scores on a scale Standard Deviation 0.0638
Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52 Week 52, Right eye, n=167, 165, 72	-0.008 Scores on a scale Standard Deviation 0.0928	0.003 Scores on a scale Standard Deviation 0.0755	-0.012 Scores on a scale Standard Deviation 0.0776

PRIMARY outcome

Timeframe: Baseline; Week 2, Week 12, Week 28, and Week 52/Early Withdrawal

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

The QT interval is an electrocardiogram (ECG) parameter that represents the electrical depolarization and repolarization of the left and right ventricles of the heart. The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the ECG. Corrected QT (QTc) is the QT interval corrected for heart rate by using Bazett's formula (QTcB) and Fridericia's formula (QTcF). 12-lead ECG measurements were perfomed at the following scheduled time points: Baseline; Week 2, Week 12, Week 28, and Week 52/Early Withdrawal. The Baseline value is defined as the value taken pre-dose at screening. The maximum post-Baseline value was derived using all scheduled, unscheduled, and Early Withdrawal ECG assessments. Maximum change from Baseline was calculated as the maximum post-Baseline value minus the value at Baseline.

Outcome measures

Measure	FF/VI 100/25 µg OD n=199 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=198 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Maximum Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF) QTcB	19.0 Milliseconds (msec) Standard Deviation 17.33	16.4 Milliseconds (msec) Standard Deviation 19.49	13.2 Milliseconds (msec) Standard Deviation 16.57
Maximum Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF) QTcF	12.8 Milliseconds (msec) Standard Deviation 14.51	11.6 Milliseconds (msec) Standard Deviation 15.60	11.4 Milliseconds (msec) Standard Deviation 12.81

PRIMARY outcome

Timeframe: 0-24 hours at Screening, Day 1, Week 28, and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Twenty-four hour Holter monitors were obtained using a 12-lead Holter monitor. The Holter monitor is worn by the participant for 24 hours, and the monitor continuously records the heart's rhythm while the monitor is worn. At the end of the 24 hour period, the data from the monitor are downloaded and transmitted to the centralized vendor for analysis and interpretation by a licensed cardiologist.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Week 28, n=95, 90, 39	77.8 beats per minute Standard Deviation 8.90	77.5 beats per minute Standard Deviation 9.01	74.9 beats per minute Standard Deviation 8.54
Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Week 52, n=88, 82, 37	78.8 beats per minute Standard Deviation 8.72	78.0 beats per minute Standard Deviation 10.15	74.8 beats per minute Standard Deviation 8.62
Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Screening, n=111, 116, 49	79.0 beats per minute Standard Deviation 8.23	79.1 beats per minute Standard Deviation 9.55	79.8 beats per minute Standard Deviation 8.75
Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Day 1, n=104, 113, 47	78.6 beats per minute Standard Deviation 7.89	78.7 beats per minute Standard Deviation 9.45	77.4 beats per minute Standard Deviation 7.66

PRIMARY outcome

Timeframe: 0-24 hours at Screening, Day 1, Week 28, and Week 52

Population: ITT Population. Only those participants available at the specified time points were analyzed (represented by n=X in the category titles). Different participants may have been analyzed at different time points, so the overall number of participants analyzed reflects everyone in the ITT Population.

Twenty-four hour Holter monitors were obtained using a 12-lead Holter monitor. Holter monitor data were transmitted to a centralized vendor for analysis and interpretation by a licensed cardiologist.

Outcome measures

Measure	FF/VI 100/25 µg OD n=201 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 Participants Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BID n=100 Participants Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Day 1, n=104, 113, 47	131.2 beats per minute Standard Deviation 18.28	130.8 beats per minute Standard Deviation 19.50	129.2 beats per minute Standard Deviation 18.77
Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Week 28, n=95, 90, 39	127.5 beats per minute Standard Deviation 17.93	127.4 beats per minute Standard Deviation 16.62	123.5 beats per minute Standard Deviation 14.93
Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Week 52, n=88, 82, 37	126.9 beats per minute Standard Deviation 18.16	128.1 beats per minute Standard Deviation 16.63	122.8 beats per minute Standard Deviation 13.89
Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data Screening, n=111, 116, 49	132.6 beats per minute Standard Deviation 17.18	132.1 beats per minute Standard Deviation 17.85	133.0 beats per minute Standard Deviation 16.17

Adverse Events

FF/VI 100/25 µg OD

Serious events: 3 serious events

Other events: 108 other events

Deaths: 0 deaths

FF/VI 200/25 µg OD

Serious events: 1 serious events

Other events: 105 other events

Deaths: 0 deaths

FP 500 µg BD

Serious events: 7 serious events

Other events: 61 other events

Deaths: 0 deaths

Serious adverse events

Measure	FF/VI 100/25 µg OD n=201 participants at risk Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 participants at risk Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BD n=100 participants at risk Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Infections and infestations Dengue Fever	0.50% 1/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Pneumonia	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Pyelonephritis Acute	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.50% 1/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Asthma	0.50% 1/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 2/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast Cancer	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Fibroadenoma of Breast	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Hepatobiliary disorders Hepatitis	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	0.50% 1/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Vascular disorders Deep Vein Thrombosis	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.

Other adverse events

Measure	FF/VI 100/25 µg OD n=201 participants at risk Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 100/25 micrograms (µg) inhalation powder once daily (OD) in the evening via the Dry Powder Inhaler (DPI), plus a placebo via DISKUS/ACCUHALER twice daily (BID), for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FF/VI 200/25 µg OD n=202 participants at risk Participants received FF/VI 200/25 µg inhalation powder OD in the evening via the DPI, plus a placebo via DISKUS/ACCUHALER BID, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.	FP 500 µg BD n=100 participants at risk Participants received Fluticasone Propionate (FP) 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Infections and infestations Upper respiratory tract infection	16.9% 34/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	14.9% 30/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	18.0% 18/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Nasopharyngitis	12.4% 25/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	9.4% 19/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	10.0% 10/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Oral candidiasis	6.0% 12/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.4% 11/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 2/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Bronchitis	3.5% 7/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	4.5% 9/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.0% 5/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Respiratory tract infection	3.0% 6/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.5% 5/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	7.0% 7/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Infections and infestations Sinusitis	4.5% 9/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 4/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.0% 5/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Nervous system disorders Headache	19.4% 39/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	17.3% 35/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	23.0% 23/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Nervous system disorders Tension headache	0.50% 1/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.00% 0/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	4.5% 9/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.4% 11/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	13.0% 13/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	3.5% 7/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.9% 12/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	11.0% 11/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Dysphonia	4.0% 8/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 6/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Respiratory, thoracic and mediastinal disorders Rhinitis allergic	3.5% 7/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 4/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 2/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Gastrointestinal disorders Abdominal pain upper	4.0% 8/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	5.4% 11/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	1.0% 1/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Gastrointestinal disorders Diarrhoea	3.5% 7/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 6/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	2.0% 2/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	4.0% 8/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	6.4% 13/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Musculoskeletal and connective tissue disorders Myalgia	2.0% 4/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.99% 2/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
General disorders Pyrexia	4.0% 8/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	6.4% 13/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	6.0% 6/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Cardiac disorders Extrasystoles	2.0% 4/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	7.4% 15/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.
Ear and labyrinth disorders Ear pain	0.00% 0/201 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	0.50% 1/202 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.	3.0% 3/100 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 52 weeks of treatment). SAEs and non-serious AEs were collected in the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received at least one dose of study medication.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER