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Fluticasone Furoate/GW642444 Inhalation Powder Long-Term Safety Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01018186
Recruitment Status : Completed
First Posted : November 23, 2009
Results First Posted : October 29, 2013
Last Update Posted : February 15, 2018
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: Fluticasone Furoate/GW642444
Drug: Fluticasone propionate
Enrollment 503
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Current Asthma Therapy at a Fixed Dose FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description 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. 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. 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. 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.
Period Title: 2-week Run-in Period
Started 617 0 0 0
Completed 503 0 0 0
Not Completed 114 0 0 0
Reason Not Completed
Protocol Violation             1             0             0             0
Lost to Follow-up             2             0             0             0
Physician Decision             3             0             0             0
Withdrawal by Subject             11             0             0             0
Did Not Meet Continuation Criteria             97             0             0             0
Period Title: 52-week Double-blind Treatment Period
Started 0 201 202 100
Completed 0 161 161 71
Not Completed 0 40 41 29
Reason Not Completed
Adverse Event             0             5             3             6
Lack of Efficacy             0             1             4             1
Protocol Violation             0             8             8             2
Protocol-defined Stopping Criteria             0             14             16             4
Lost to Follow-up             0             1             3             4
Physician Decision             0             1             0             3
Withdrawal by Subject             0             10             7             9
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID Total
Hide Arm/Group Description 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. 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. 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 of all reporting groups
Overall Number of Baseline Participants 201 202 100 503
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 201 participants 202 participants 100 participants 503 participants
39.7  (15.85) 38.5  (15.64) 38.6  (15.97) 39.0  (15.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 201 participants 202 participants 100 participants 503 participants
Female
130
  64.7%
124
  61.4%
62
  62.0%
316
  62.8%
Male
71
  35.3%
78
  38.6%
38
  38.0%
187
  37.2%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 201 participants 202 participants 100 participants 503 participants
African American/African Heritage 15 17 6 38
Asian - East Asian Heritage 0 0 1 1
Asian - South East Asian Heritage 50 51 24 125
Asian - Mixed Race 0 0 1 1
White - Arabic/North African Heritage 4 1 0 5
White - White/Caucasian/European Heritage 129 132 68 329
White - Mixed Race 2 1 0 3
Mixed Race 1 0 0 1
1.Primary Outcome
Title Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) During the Treatment Period
Hide Description 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.
Time Frame From the start of study medication until Visit 11 (Week 52)/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study medication
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
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.
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.
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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
Any AE 139 134 73
Any SAE 3 1 7
2.Primary Outcome
Title Number of Participants With Severe Asthma Exacerbations During the Treatment Period
Hide Description 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.
Time Frame From the start of study medication until Visit 11 (Week 52)/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
3 6 3
3.Primary Outcome
Title Change From Baseline in Albumin and Total Protein at Week 12, Week 28, and Week 52/Early Withdrawal
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Grams per liter (G/L)
Albumin, Week 12, n=172, 182, 87 0.1  (2.69) 0.2  (2.87) -0.5  (2.64)
Albumin, Week 28, n=180, 176, 79 -0.2  (2.68) -0.3  (2.79) -0.4  (2.76)
Albumin, Week 52, n=157, 159, 67 -0.1  (2.81) -0.8  (2.72) -0.5  (2.54)
Total Protein, Week 12, n=172, 182, 87 -0.6  (4.13) -0.1  (4.50) -0.6  (3.96)
Total Protein, Week 28, n=180, 176, 79 -1.1  (3.90) -1.0  (4.47) -0.5  (4.33)
Total Protein, Week 52, n=157, 159, 67 -0.7  (4.53) -1.4  (4.60) -1.0  (4.38)
4.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: International units per liter (IU/L)
ALP, Week 12, n=158, 165, 84 -3.0  (18.76) -2.6  (29.65) -4.7  (24.47)
ALP, Week 28, n=180, 176, 79 -1.0  (32.68) -5.8  (30.56) -5.7  (24.33)
ALP, Week 52, n=157, 157, 67 -4.0  (30.67) -7.2  (34.65) -9.3  (27.54)
ALT, Week 12, n=172, 182, 87 -1.0  (10.43) -0.2  (13.51) -0.3  (12.03)
ALT, Week 28, n=180, 176, 79 -1.6  (10.08) -0.1  (10.59) 0.4  (11.96)
ALT, Week 52, n=157, 159, 67 -1.8  (12.40) -1.3  (11.13) -0.1  (9.78)
AST, Week 12, n=171, 181, 87 -0.9  (8.07) -0.3  (12.05) 0.3  (8.69)
AST, Week 28, n=179, 176, 79 -1.4  (8.42) -0.9  (11.60) 1.3  (10.65)
AST, Week 52, n=156, 158, 67 -1.8  (8.78) -1.9  (11.21) -0.2  (9.22)
GGT, Week 12, n=172, 182, 87 0.9  (12.90) -0.1  (18.23) -1.7  (12.12)
GGT, Week 28, n=180, 176, 79 3.3  (33.79) -0.6  (17.63) -0.2  (11.85)
GGT, Week 52, n=157, 159, 67 2.7  (40.34) -2.7  (15.99) -0.5  (13.30)
Creatinine Kinase, Week 12, n=172, 181, 87 10.8  (92.06) -11.5  (254.71) -18.3  (223.59)
Creatinine Kinase, Week 28, n=180, 176, 79 2.0  (68.72) -9.9  (247.61) 15.3  (441.68)
Creatinine Kinase, Week 52, n=157, 159, 67 -0.7  (69.12) -16.8  (266.48) -27.7  (274.14)
5.Primary Outcome
Title Change From Baseline in Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, and Creatinine at Week 12, Week 28, and Week 52/Early Withdrawal
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Micromoles per liter (µmol/L)
Direct bilirubin, Week 12, n=172, 182, 87 -0.3  (0.99) -0.3  (0.98) -0.2  (0.93)
Direct bilirubin, Week 28, n=180, 176, 79 -0.3  (0.97) -0.2  (1.01) -0.1  (0.94)
Direct bilirubin, Week 52, n=157, 159, 67 -0.4  (0.99) -0.4  (1.00) -0.2  (0.90)
Indirect bilirubin, Week 12, n=172, 182, 87 -1.4  (3.11) -0.8  (2.86) -0.6  (3.04)
Indirect bilirubin, Week 28, n=180, 175, 79 -1.3  (3.09) -0.9  (2.87) -0.4  (3.14)
Indirect bilirubin, Week 52, n=157, 159, 67 -2.0  (3.08) -1.6  (2.51) -0.8  (2.68)
Total Bilirubin, Week 12, n=172, 182, 87 -1.7  (3.62) -1.1  (3.46) -0.8  (3.44)
Total Bilirubin, Week 28, n=180, 175, 79 -1.6  (3.61) -1.2  (3.55) -0.5  (3.46)
Total Bilirubin, Week 52, n=157, 159, 67 -2.4  (3.58) -2.0  (2.93) -1.0  (3.14)
Creatinine, Week 12, n=172, 181, 87 3.00  (10.214) 3.18  (7.983) 3.99  (8.056)
Creatinine, Week 28, n=180, 176, 79 7.03  (19.264) 5.10  (10.316) 17.43  (92.175)
Creatinine, Week 52, n=157, 159, 67 2.74  (9.450) 3.14  (11.310) 3.32  (9.982)
6.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Millimoles per liter (mmol/L)
Chloride, Week 12, n=172, 182, 87 -0.7  (3.43) -0.4  (3.50) 0.1  (2.28)
Chloride, Week 28, n=180, 176, 79 -0.1  (2.50) 0.2  (2.73) -0.1  (2.54)
Chloride, Week 52, n=157, 159, 67 -0.5  (2.51) 0.0  (2.67) -0.3  (2.31)
CO2 content/bicarbonate, Week 12, n=171, 181, 87 -0.7  (3.13) -0.8  (2.91) -0.2  (2.72)
CO2 content/bicarbonate, Week 28, n=179, 176, 79 0.3  (2.90) 0.1  (2.61) 0.9  (2.60)
CO2 content/bicarbonate, Week 52, n=156, 158, 67 -0.1  (2.53) 0.1  (2.51) 0.5  (2.55)
Glucose, Week 12, n=172, 181, 87 0.33  (1.873) 0.17  (2.085) 0.10  (1.233)
Glucose, Week 28, n=180, 175, 79 0.21  (1.547) 0.16  (1.556) 0.02  (1.442)
Glucose, Week 52, n=157, 159, 67 0.45  (1.839) 0.11  (1.426) -0.20  (1.191)
Potassium, Week 12, n=157, 165, 84 -0.09  (0.572) 0.00  (0.721) -0.03  (0.606)
Potassium, Week 28, n=179, 176, 79 -0.12  (0.467) -0.15  (0.449) 0.02  (0.617)
Potassium, Week 52, n=156, 156, 67 -0.18  (0.461) -0.12  (0.535) -0.10  (0.446)
Sodium, Week 12, n=172, 182, 87 -0.1  (2.47) 0.2  (2.61) -0.0  (2.24)
Sodium, Week 28, n=180, 176, 79 0.0  (2.46) 0.2  (2.65) 0.3  (2.74)
Sodium, Week 52, n=157, 159, 67 -0.2  (2.57) 0.1  (2.52) 0.0  (2.80)
Urea/BUN, Week 12, n=172, 182, 87 0.24  (1.299) 0.36  (1.237) 0.02  (1.757)
Urea/BUN, Week 28, n=180, 176, 79 0.16  (1.460) 0.14  (1.124) 0.41  (2.676)
Urea/BUN, Week 52, n=157, 159, 67 0.15  (1.244) 0.13  (1.479) -0.04  (1.900)
7.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 101
Mean (Standard Deviation)
Unit of Measure: Percentage
Basophils, Week 12, n=171, 170, 86 -0.01  (0.330) -0.06  (0.331) -0.08  (0.320)
Basophils, Week 28, n=169, 169, 77 -0.01  (0.319) 0.00  (0.338) -0.06  (0.310)
Basophils, Week 52, n=155, 155, 71 0.02  (0.314) -0.03  (0.279) -0.07  (0.319)
Eosinophils, Week 12, n=171, 170, 86 -0.35  (4.048) -0.88  (3.825) -1.23  (3.391)
Eosinophils, Week 28, n=169, 169, 77 -0.97  (3.991) -1.34  (3.774) -1.63  (3.574)
Eosinophils, Week 52, n=155, 155, 71 -0.84  (4.096) -0.90  (3.946) -1.19  (3.611)
Lymphocytes, Week 12, n=171, 170, 86 -0.57  (9.280) -0.91  (8.414) -1.72  (8.449)
Lymphocytes, Week 28, n=169, 169, 77 -1.11  (8.816) -1.31  (10.200) -1.66  (11.054)
Lymphocytes, Week 52, n=155, 155, 71 1.34  (9.389) -0.03  (10.137) -0.97  (8.532)
Monocytes, Week 12, n=171, 170, 86 -0.60  (2.692) -0.47  (2.500) -0.86  (3.147)
Monocytes, Week 28, n=169, 169, 77 -0.66  (2.594) -0.53  (2.706) -0.84  (3.063)
Monocytes, Week 52, n=155, 155, 71 -0.19  (2.439) 0.31  (2.598) -0.30  (2.337)
Segmented neutrophils, Week 12, n=171, 170, 86 1.54  (10.883) 2.32  (9.635) 3.89  (11.397)
Segmented neutrophils, Week 28, n=169, 169, 77 2.71  (10.221) 3.18  (12.008) 4.19  (13.745)
Segmented neutrophils, Week 52, n=155, 155, 71 -0.33  (10.687) 0.66  (11.768) 2.54  (10.112)
8.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: 10^9 cells per liter (GI/L)
Eosinophil count, Week 12, n=171, 170, 86 -0.010  (0.3226) -0.057  (0.3841) -0.073  (0.2220)
Eosinophil count, Week 28, n=169, 169, 77 -0.039  (0.3310) -0.083  (0.3698) -0.083  (0.2363)
Eosinophil count, Week 52, n=155, 155, 71 -0.023  (0.3273) -0.037  (0.3171) -0.044  (0.2539)
Total ANC, Week 12, n=171, 170, 86 0.392  (1.6161) 0.469  (1.6904) 0.493  (1.7488)
Total ANC, Week 28, n=169, 169, 77 0.632  (1.5922) 0.679  (2.0157) 0.750  (2.0130)
Total ANC, Week 52, n=136, 136, 60 0.524  (1.4589) 0.612  (1.9100) 0.748  (1.7946)
Platelet Count, Week 12, n=167, 159, 78 -1.3  (39.44) 1.5  (68.10) 1.5  (43.26)
Platelet Count, Week 28, n=164, 165, 74 1.0  (44.49) 3.5  (35.06) 12.4  (43.59)
Platelet Count, Week 52, n=147, 151, 68 1.8  (43.80) 4.6  (38.49) 16.4  (50.99)
WBC Count, Week 12, n=173, 170, 86 0.51  (1.744) 0.50  (2.007) 0.39  (1.906)
WBC Count, Week 28, n=170, 169, 77 0.74  (1.758) 0.74  (2.103) 0.79  (2.028)
WBC Count, Week 52, n=156, 156, 71 0.91  (1.639) 0.83  (2.046) 1.01  (1.909)
9.Primary Outcome
Title Change From Baseline in Hematocrit at Week 12, Week 28, and Week 52/Early Withdrawal
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Proportion of 1.0
Week 12, n=176, 172, 86 -0.0073  (0.02307) -0.0013  (0.02654) -0.0025  (0.02318)
Week 28, n=172, 170, 77 -0.0017  (0.02213) -0.0005  (0.02464) -0.0028  (0.02168)
Week 52, n=157, 159, 72 -0.0027  (0.02906) -0.0021  (0.02467) -0.0045  (0.02495)
10.Primary Outcome
Title Change From Baseline in Hemoglobin at Week 12, Week 28, and Week 52/Early Withdrawal
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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. Participnts were provided albuterol/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Participants received FP 500 µg BID via DISKUS/ACCUHALER, plus a placebo via the DPI OD in the evening, for 52 weeks. Participants were provided albutero/salbutamol inhalation aerosol to be used as rescue medication during the Treatment Period.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Grams per liter (g/L)
Week 12, n=176, 172, 86 -3.4  (7.48) -1.8  (8.25) -2.0  (7.67)
Week 28, n=172, 170, 77 -2.1  (7.64) -2.2  (8.11) -2.4  (7.72)
Week 52, n=157, 159, 72 -2.6  (10.26) -2.9  (7.47) -3.0  (8.77)
11.Primary Outcome
Title Number of Participants With the Indicated Shift From Baseline to High, Normal or no Change, and Low Post-Baseline Values for Urinary Cortisol Excretion
Hide Description 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.
Time Frame Baseline; Week 12, Week 28, and Week 52/Early Withdrawal
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
Week 12: To high, n=139, 140, 78 6 7 2
Week 12: To normal or no change, n=139, 140, 78 131 128 67
Week 12: To low, n=139, 140, 78 2 5 9
Week 28: To high, n=135, 131, 59 8 8 3
Week 28: To normal or no change, n=135, 131, 59 123 120 47
Week 28: To low, n=135, 131, 59 4 3 9
Week 52: To high, n=134, 140, 65 10 7 4
Week 52: To normal or no change , n=134, 140, 65 119 131 57
Week 52: To low, n=134, 140, 65 5 2 4
AVBP: To high, n=156, 156, 83 25 21 8
AVBP: To normal or no change, n=156, 156, 83 119 126 58
AVBP: To low, n=156, 156, 83 12 9 17
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
1.34 to 2.08
Estimation Comments Ratio of FF/VI 100/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 12
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.29 to 2.13
Estimation Comments Ratio of FF/VI 100/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 28
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.83 to 1.33
Estimation Comments Ratio of FF/VI 100/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 52
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
1.22 to 1.89
Estimation Comments Ratio of FF/VI 200/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 12
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
1.11 to 1.84
Estimation Comments Ratio of FF/VI 200/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 28
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.87 to 1.38
Estimation Comments Ratio of FF/VI 200/25 OD versus FP 500 BD to Baseline of 24-Hour Urinary Cortisol Excretion at Week 52
12.Primary Outcome
Title Ratio of 24-hour Urinary Cortisol Excretion at Week 12 to Baseline
Hide Description 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.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 129 129 71
Measure Type: Number
Unit of Measure: Ratio of LSGM of UCE to Baseline
1.03 0.93 0.61
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.67
Confidence Interval (2-Sided) 95%
1.34 to 2.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.52
Confidence Interval (2-Sided) 95%
1.22 to 1.89
Estimation Comments [Not Specified]
13.Primary Outcome
Title Ratio of 24-hour Urinary Cortisol Excretion at Week 28 to Baseline
Hide Description 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.
Time Frame Baseline and Week 28
Hide Outcome Measure Data
Hide Analysis Population Description
UC Population. Only those participants available at the specified time point were analyzed.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 128 121 56
Measure Type: Number
Unit of Measure: Ratio of LSGM of UCE to Baseline
1.05 0.91 0.64
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.65
Confidence Interval (2-Sided) 95%
1.29 to 2.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.006
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.43
Confidence Interval (2-Sided) 95%
1.11 to 1.84
Estimation Comments [Not Specified]
14.Primary Outcome
Title Ratio of 24-hour Urinary Cortisol Excretion at Week 52 to Baseline
Hide Description 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.
Time Frame Baseline and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
UC Population. Only those participants available at the specified time point were analyzed.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 125 127 60
Measure Type: Number
Unit of Measure: Ratio of LSGM of UCE to Baseline
1.00 1.04 0.95
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.674
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.83 to 1.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 µg OD, FP 500 µg BID
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.444
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Ratio of LSGM to Baseline
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.87 to 1.38
Estimation Comments [Not Specified]
15.Primary Outcome
Title Number of Participants With Evidence of Oral Candidiasis at Any Time Post-Baseline
Hide Description 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.
Time Frame From Baseline until Visit 11/Early Withdrawal (52 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 199 200 100
Measure Type: Number
Unit of Measure: participants
Evidence of oral candidiasis 15 14 5
Positive culture swab 13 11 3
Negative culture swab 1 2 2
No swab result available 1 1 0
16.Primary Outcome
Title Maximum Change From Baseline in Systolic Blood Pressure (SBP) and Minimum Change From Baseline in Diastolic Blood Pressure (DBP)
Hide Description 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.
Time Frame From Baseline until Visit 11/Early Withdrawal (52 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Millimeters of mercury (mmHg)
Maximum post-Baseline change in SBP 10.2  (11.05) 10.0  (10.17) 11.3  (11.09)
Minimum post-Baseline change in DBP -8.9  (7.70) -9.0  (8.44) -8.0  (7.76)
17.Primary Outcome
Title Maximum Change From Baseline in Pulse Rate
Hide Description 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.
Time Frame From Baseline until Visit 11/Early Withdrawal (52 weeks)
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Beats per minute
10.5  (9.30) 10.0  (10.05) 7.5  (8.29)
18.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 28, and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
Left eye, <0.3, Week 28, n=179, 177, 80 174 175 79
Left eye, >=0.3 and <0.5, Week 28, n=179, 177, 80 5 2 1
Left eye, >=0.5, Week 28, n=179, 177, 80 0 0 0
Right eye, <0.3, Week 28, n=179, 177, 80 175 175 80
Right eye, >=0.3 and <0.5, Week 28, n=179, 177, 80 4 2 0
Right eye, >=0.5, Week 28, n=179, 177, 80 0 0 0
Left eye, <0.3, Week 52, n=167, 166, 72 163 164 72
Left eye, >=0.3 and <0.5, Week 52, n=167, 166, 72 2 1 0
Left eye, >=0.5, Week 52, n=167, 166, 72 2 1 0
Right eye, <0.3, Week 52, n=167, 166, 72 163 164 72
Right eye, >=0.3 and <0.5, Week 52, n=167, 166, 72 3 1 0
Right eye, >=0.5, Week 52, n=167, 166, 72 1 1 0
19.Primary Outcome
Title Number of Participants With the Indicated Change From Baseline in Intraocular Pressure (IOP) at Week 28 and Week 52
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
Left eye, <0 mmHg, Week 28, n=179, 177, 80 71 78 32
Left eye, >=0 to <4 mmHg, Week 28, n=179, 177, 80 101 92 46
Left eye, >=4 to <7 mmHg, Week 28, n=179, 177, 80 7 6 2
Left eye, >=7 to <11 mmHg, Week 28, n=179, 177, 80 0 1 0
Left eye, >=11 mmHg, Week 28, n=179, 177, 80 0 0 0
Right eye, <0 mmHg, Week 28, n=179, 177, 80 73 61 38
Right eye, >=0 to <4 mmHg, Week 28, n=179, 177, 80 101 110 38
Right eye, >=4 to <7 mmHg, Week 28, n=179, 177, 80 5 5 4
Right eye, >=7 to <11 mmHg,Week 28, n=179, 177, 80 0 1 0
Right eye, >=11 mmHg, Week 28, n=179, 177, 80 0 0 0
Left eye, <0 mmHg, Week 52, n=167, 166, 72 66 69 33
Left eye, >=0 to <4 mmHg, Week 52, n=167, 166, 72 88 83 36
Left eye, >=4 to <7 mmHg, Week 52, n=167, 166, 72 11 14 3
Left eye, >=7 to <11 mmHg, Week 52, n=167, 166, 72 2 0 0
Left eye, >=11 mmHg, Week 52, n=167, 166, 72 0 0 0
Right eye, <0 mmHg, Week 52, n=167, 166, 72 63 61 32
Right eye, >=0 to <4 mmHg, Week 52, n=167, 166, 72 94 93 40
Right eye, >=4 to <7 mmHg, Week 52, n=167, 166, 72 10 12 0
Right eye, >=7 to <11 mmHg, Week 52, n=167,166, 72 0 0 0
Right eye, >=11 mmHg, Week 52, n=167, 166, 72 0 0 0
20.Primary Outcome
Title Change From Baseline in Horizontal Cup-to-disc Ratio at Week 28 and Week 52
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: ratio
Left eye, Week 28, n=179, 177, 80 0.5  (4.79) -0.2  (5.11) 0.5  (4.87)
Right eye, Week 28, n=179, 177, 80 0.2  (4.17) -0.2  (6.49) 0.5  (5.10)
Left eye, Week 52, n=167, 166, 72 0.4  (5.86) 0.2  (4.89) 0.3  (4.77)
Right eye, Week 52, n=167, 166, 72 0.1  (4.63) 0.2  (5.57) 0.0  (5.26)
21.Primary Outcome
Title 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
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Measure Type: Number
Unit of Measure: participants
Left eye, <0.3, Week 28, n=179, 177, 80 167 166 75
Left eye, >=0.3 and <0.5, Week 28, n=179, 177, 80 6 5 4
Left eye, >=0.5, Week 28, n=179, 177, 80 6 6 1
Right eye, <0.3, Week 28, n=179, 177, 80 169 172 75
Right eye, >=0.3 and <0.5, Week 28, n=179, 177, 80 5 1 4
Right eye, >=0.5, Week 28, n=179, 177, 80 5 4 1
Left eye, <0.3, Week 52, n=167, 166, 72 154 156 66
Left eye, >=0.3 and <0.5, Week 52, n=167, 166, 72 7 4 3
Left eye, >=0.5, Week 52, n=167, 166, 72 6 6 3
Right eye, <0.3, Week 52, n=167, 166, 72 151 158 69
Right eye, >=0.3 and <0.5, Week 52, n=167, 166, 72 11 2 2
Right eye, >=0.5, Week 52, n=167, 166, 72 5 6 1
22.Primary Outcome
Title Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Color (NC) at Week 28 and Week 52
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 28, Left eye, n=179, 177, 80 0.01  (0.282) 0.00  (0.284) -0.02  (0.299)
Week 28, Right eye, n=179, 177, 80 0.01  (0.292) 0.1  (0.292) -0.02  (0.294)
Week 52, Left eye, n=167, 166, 72 0.02  (0.281) -0.2  (0.357) 0.00  (0.340)
Week 52, Right eye, n=167, 166, 72 0.02  (0.304) 0.00  (0.339) 0.01  (0.336)
23.Primary Outcome
Title Change From Baseline in Lens Opacities Classification System, Version III (LOCS III) Nuclear Opalescence (NO) at Week 28 and Week 52
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 28, Left eye, n=179, 177, 80 0.02  (0.236) 0.03  (0.316) -0.02  (0.270)
Week 28, Right eye, n=179, 177, 80 0.01  (0.256) 0.03  (0.303) -0.03  (0.272)
Week 52, Left eye, n=167, 166, 72 0.01  (0.330) 0.03  (0.303) 0.01  (0.369)
Week 52, Right eye, n=167, 166, 72 0.00  (0.351) 0.04  (0.282) 0.02  (0.371)
24.Primary Outcome
Title Change From Baseline in the Logarithm of the Minimum Angle of Resolution (LogMAR) Visual Acuity at Week 28 and Week 52
Hide Description 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.
Time Frame Baseline; Week 28 and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 28, Left eye, n=179, 176, 80 -0.008  (0.0723) -0.010  (0.0706) -0.004  (0.0685)
Week 28, Right eye, n=179, 176, 80 -0.003  (0.0739) -0.001  (0.0699) -0.008  (0.0584)
Week 52, Left eye, n=167, 165, 72 -0.011  (0.0747) -0.012  (0.0739) -0.007  (0.0638)
Week 52, Right eye, n=167, 165, 72 -0.008  (0.0928) 0.003  (0.0755) -0.012  (0.0776)
25.Primary Outcome
Title Maximum Change From Baseline in the QT Interval Using Bazett's Correction (QTcB) and QT Interval Using Fridericia's Correction (QTcF)
Hide Description 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.
Time Frame Baseline; Week 2, Week 12, Week 28, and Week 52/Early Withdrawal
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Hide Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 199 198 100
Mean (Standard Deviation)
Unit of Measure: Milliseconds (msec)
QTcB 19.0  (17.33) 16.4  (19.49) 13.2  (16.57)
QTcF 12.8  (14.51) 11.6  (15.60) 11.4  (12.81)
26.Primary Outcome
Title Mean 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data
Hide Description 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.
Time Frame 0-24 hours at Screening, Day 1, Week 28, and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: beats per minute
Screening, n=111, 116, 49 79.0  (8.23) 79.1  (9.55) 79.8  (8.75)
Day 1, n=104, 113, 47 78.6  (7.89) 78.7  (9.45) 77.4  (7.66)
Week 28, n=95, 90, 39 77.8  (8.90) 77.5  (9.01) 74.9  (8.54)
Week 52, n=88, 82, 37 78.8  (8.72) 78.0  (10.15) 74.8  (8.62)
27.Primary Outcome
Title Maximum 24 Hour Holter Heart Rate for Participants With at Least 16 Hours of Recorded Data
Hide Description 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.
Time Frame 0-24 hours at Screening, Day 1, Week 28, and Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BID
Hide Arm/Group Description:
Participants received FF/VI 100/25 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.
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.
Participants received 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.
Overall Number of Participants Analyzed 201 202 100
Mean (Standard Deviation)
Unit of Measure: beats per minute
Screening, n=111, 116, 49 132.6  (17.18) 132.1  (17.85) 133.0  (16.17)
Day 1, n=104, 113, 47 131.2  (18.28) 130.8  (19.50) 129.2  (18.77)
Week 28, n=95, 90, 39 127.5  (17.93) 127.4  (16.62) 123.5  (14.93)
Week 52, n=88, 82, 37 126.9  (18.16) 128.1  (16.63) 122.8  (13.89)
Time Frame 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).
Adverse Event Reporting Description 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.
 
Arm/Group Title FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BD
Hide Arm/Group Description 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. 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. 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.
All-Cause Mortality
FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/201 (1.49%)   1/202 (0.50%)   7/100 (7.00%) 
Hepatobiliary disorders       
Hepatitis  1  0/201 (0.00%)  0/202 (0.00%)  1/100 (1.00%) 
Infections and infestations       
Dengue Fever  1  1/201 (0.50%)  0/202 (0.00%)  0/100 (0.00%) 
Pneumonia  1  0/201 (0.00%)  0/202 (0.00%)  1/100 (1.00%) 
Pyelonephritis Acute  1  0/201 (0.00%)  1/202 (0.50%)  0/100 (0.00%) 
Musculoskeletal and connective tissue disorders       
Myalgia  1  1/201 (0.50%)  0/202 (0.00%)  0/100 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Breast Cancer  1  0/201 (0.00%)  0/202 (0.00%)  1/100 (1.00%) 
Fibroadenoma of Breast  1  0/201 (0.00%)  0/202 (0.00%)  1/100 (1.00%) 
Respiratory, thoracic and mediastinal disorders       
Asthma  1  1/201 (0.50%)  0/202 (0.00%)  2/100 (2.00%) 
Vascular disorders       
Deep Vein Thrombosis  1  0/201 (0.00%)  0/202 (0.00%)  1/100 (1.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
FF/VI 100/25 µg OD FF/VI 200/25 µg OD FP 500 µg BD
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   108/201 (53.73%)   105/202 (51.98%)   61/100 (61.00%) 
Cardiac disorders       
Extrasystoles  1  4/201 (1.99%)  15/202 (7.43%)  3/100 (3.00%) 
Ear and labyrinth disorders       
Ear pain  1  0/201 (0.00%)  1/202 (0.50%)  3/100 (3.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  8/201 (3.98%)  11/202 (5.45%)  1/100 (1.00%) 
Diarrhoea  1  7/201 (3.48%)  6/202 (2.97%)  2/100 (2.00%) 
General disorders       
Pyrexia  1  8/201 (3.98%)  13/202 (6.44%)  6/100 (6.00%) 
Infections and infestations       
Upper respiratory tract infection  1  34/201 (16.92%)  30/202 (14.85%)  18/100 (18.00%) 
Nasopharyngitis  1  25/201 (12.44%)  19/202 (9.41%)  10/100 (10.00%) 
Oral candidiasis  1  12/201 (5.97%)  11/202 (5.45%)  2/100 (2.00%) 
Bronchitis  1  7/201 (3.48%)  9/202 (4.46%)  5/100 (5.00%) 
Respiratory tract infection  1  6/201 (2.99%)  5/202 (2.48%)  7/100 (7.00%) 
Sinusitis  1  9/201 (4.48%)  4/202 (1.98%)  5/100 (5.00%) 
Musculoskeletal and connective tissue disorders       
Back pain  1  8/201 (3.98%)  13/202 (6.44%)  3/100 (3.00%) 
Myalgia  1  4/201 (1.99%)  2/202 (0.99%)  3/100 (3.00%) 
Nervous system disorders       
Headache  1  39/201 (19.40%)  35/202 (17.33%)  23/100 (23.00%) 
Tension headache  1  1/201 (0.50%)  0/202 (0.00%)  3/100 (3.00%) 
Respiratory, thoracic and mediastinal disorders       
Cough  1  9/201 (4.48%)  11/202 (5.45%)  13/100 (13.00%) 
Oropharyngeal pain  1  7/201 (3.48%)  12/202 (5.94%)  11/100 (11.00%) 
Dysphonia  1  8/201 (3.98%)  6/202 (2.97%)  3/100 (3.00%) 
Rhinitis allergic  1  7/201 (3.48%)  4/202 (1.98%)  2/100 (2.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
Results Point of Contact
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Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01018186    
Other Study ID Numbers: 106839
First Submitted: November 5, 2009
First Posted: November 23, 2009
Results First Submitted: June 6, 2013
Results First Posted: October 29, 2013
Last Update Posted: February 15, 2018