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Trial record 1 of 1 for:    205715
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A Phase III Parallel Group Study, Comparing the Efficacy, Safety and Tolerability of the Fixed Dose Combination (FDC) of Fluticasone Furoate+Umeclidinium Bromide+Vilanterol (FF/UMEC/VI) With the FDC of FF/VI in Subjects With Inadequately Controlled Asthma

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ClinicalTrials.gov Identifier: NCT02924688
Recruitment Status : Completed
First Posted : October 5, 2016
Results First Posted : February 21, 2020
Last Update Posted : March 26, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Asthma
Interventions Drug: FF/UMEC/VI (100/31.25/25) mcg
Drug: FF/UMEC/VI (100/62.5/25) mcg
Drug: FF/UMEC/VI (200/31.25/25) mcg
Drug: FF/UMEC/VI (200/62.5/25) mcg
Drug: FF/VI (100/25) mcg
Drug: FF/VI (200/25) mcg
Drug: Fluticasone/salmeterol (FSC)
Drug: Albuterol/salbutamol
Device: ELLIPTA DPI
Device: DISKUS DPI
Device: METERED-DOSE INHALER (MDI)
Enrollment 2436
Recruitment Details Participants were enrolled from 322 centers across 15 countries.
Pre-assignment Details Total 5185 participants were screened and 2436 participants were enrolled into the study and received the study treatment.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Period Title: Overall Study
Started 407 405 406 406 404 408
Completed 374 374 383 378 381 384
Not Completed 33 31 23 28 23 24
Reason Not Completed
Adverse Event             9             3             2             2             3             2
Lack of Efficacy             2             3             4             2             1             1
Protocol Violation             3             7             5             6             2             2
Protocol defined withdrawal criteria met             1             0             1             1             1             0
Lost to Follow-up             2             4             2             4             2             4
Physician Decision             2             1             0             1             1             1
Withdrawal by Subject             14             13             9             12             13             14
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg Total
Hide Arm/Group Description Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Total of all reporting groups
Overall Number of Baseline Participants 407 405 406 406 404 408 2436
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 407 participants 405 participants 406 participants 406 participants 404 participants 408 participants 2436 participants
53.3  (13.03) 51.7  (13.27) 52.9  (13.39) 53.9  (13.30) 53.5  (13.12) 53.7  (12.50) 53.2  (13.11)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 407 participants 405 participants 406 participants 406 participants 404 participants 408 participants 2436 participants
Female
254
  62.4%
262
  64.7%
248
  61.1%
252
  62.1%
240
  59.4%
258
  63.2%
1514
  62.2%
Male
153
  37.6%
143
  35.3%
158
  38.9%
154
  37.9%
164
  40.6%
150
  36.8%
922
  37.8%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race Number Analyzed 407 participants 405 participants 406 participants 406 participants 404 participants 408 participants 2436 participants
Black or African American (AA)
20
   4.9%
21
   5.2%
17
   4.2%
26
   6.4%
11
   2.7%
24
   5.9%
119
   4.9%
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.5%
2
   0.5%
4
   0.2%
Asian-Central/South Asian Heritage (H.)
5
   1.2%
4
   1.0%
1
   0.2%
5
   1.2%
9
   2.2%
0
   0.0%
24
   1.0%
Asian-Japanese H./East Asian H./SouthEast Asian H.
54
  13.3%
55
  13.6%
50
  12.3%
53
  13.1%
55
  13.6%
52
  12.7%
319
  13.1%
Mixed Asian Race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
0
   0.0%
1
   0.0%
Native Hawaiian or other Pacific Islander
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.2%
1
   0.2%
3
   0.1%
White
326
  80.1%
319
  78.8%
338
  83.3%
316
  77.8%
325
  80.4%
326
  79.9%
1950
  80.0%
American Indian or Alaska Native and Black or AA
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.0%
American Indian or Alaska Native and White
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.5%
3
   0.1%
Asian and Black or African American and White
0
   0.0%
1
   0.2%
0
   0.0%
2
   0.5%
0
   0.0%
0
   0.0%
3
   0.1%
Asian and White
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.0%
Black or African American and White
1
   0.2%
2
   0.5%
0
   0.0%
3
   0.7%
0
   0.0%
1
   0.2%
7
   0.3%
Missing
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.2%
0
   0.0%
0
   0.0%
1
   0.0%
1.Primary Outcome
Title Mean Change From Baseline in Trough Forced Expiratory Volume in 1 Second (FEV1) at Week 24
Hide Description FEV1 is a measure of lung function and is defined as the maximal volume of air that can be forcefully exhaled in one second. Trough FEV1 on treatment is defined as the highest FEV1 value obtained prior to the morning dose of investigational product. Baseline value is the last acceptable/borderline acceptable pre-dose FEV1 prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at Week 24 minus the Baseline value. Intent-to-Treat (ITT) Population comprised of all randomized participants, excluding those who were randomized in error, who did not receive the study drug. Treatment policy estimand was assessed, including all on- and post-treatment data. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement. Mixed Model Repeated Measures(MMRM) was used.
Time Frame Baseline (pre-dose at Day 1) and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data point were analyzed. Participants with Baseline value and at least one post-baseline measurement were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 400 399 404 403 399 405
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.024  (0.0157) 0.120  (0.0157) 0.134  (0.0155) 0.076  (0.0156) 0.157  (0.0156) 0.168  (0.0155)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study inhaled corticosteroids (ICS) dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.096
Confidence Interval (2-Sided) 95%
0.052 to 0.139
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0222
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.110
Confidence Interval (2-Sided) 95%
0.066 to 0.153
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0221
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.082
Confidence Interval (2-Sided) 95%
0.039 to 0.125
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0221
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.092
Confidence Interval (2-Sided) 95%
0.049 to 0.135
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0220
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Annualized Rate of Moderate and Severe Asthma Exacerbations
Hide Description A moderate asthma exacerbation is considered to be a deterioration in asthma symptoms or in lung function, or increased rescue bronchodilator use lasting for at least 2 days or more, but not be severe enough to warrant systemic corticosteroid use (or a doubling or more of the maintenance systemic corticosteroid dose, if applicable) for 3 days or more and/or hospitalization. It is an event that, when recognized, should result in a temporary change in treatment, to prevent it from becoming severe. A severe asthma exacerbation is defined as the deterioration of asthma requiring the use of systemic corticosteroids (tablets,suspension or injection), or an increase from a stable maintenance dose (For participants receiving maintenance systemic corticosteroids, at least double the maintenance systemic corticosteroid dose for at least 3 days is required), for at least 3 days or an inpatient hospitalization or emergency department visit because of asthma, requiring systemic corticosteroids.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only participants with at least one day on study post-randomization were analyzed. Analysis used pooled data from two FF/UMEC/VI arms for each fixed UMEC dose compared to pooled data from two FF/VI arms to provide a more precise estimate for the treatment effect of the addition of UMEC to FF/VI.
Arm/Group Title FF/VI FF/UMEC/VI (UMEC 31.25 mcg) FF/UMEC/VI (UMEC 62.5 mcg)
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg or 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/31.25/25 mcg or 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/62.5/25 mcg or 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 813 809 814
Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per year
0.70
(0.61 to 0.80)
0.68
(0.60 to 0.78)
0.61
(0.53 to 0.70)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 31.25 mcg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.778
Comments p-value was calculated using Generalized linear model with covariates for age, sex, region, treatment group, stratification by pre-study ICS dosage at screening, and severe asthma exacerbations in the previous year (0, 1, >=2).
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.97
Confidence Interval (2-Sided) 95%
0.81 to 1.17
Estimation Comments Treatment policy estimand was assessed, including all on- and post-treatment data.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 62.5 mcg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.151
Comments p-value was calculated using Generalized linear model with covariates for age, sex, region, treatment group, stratification by pre-study ICS dosage at screening, and severe asthma exacerbations in the previous year (0, 1, >=2).
Method Negative Binomial Model
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.72 to 1.05
Estimation Comments Treatment policy estimand was assessed, including all on- and post-treatment data.
3.Secondary Outcome
Title Mean Change From Baseline in Clinic FEV1 at 3 Hours Post Study Treatment at Week 24
Hide Description FEV1 is a measure of lung function and is defined as the maximal volume of air that can be forcefully exhaled in one second. Baseline value is the last acceptable/borderline acceptable pre-dose FEV1 prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at Week 24 (recorded at 3 hours post dose) minus the Baseline value.
Time Frame Baseline (pre-dose at Day 1) and 3 hours post dose at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with available Baseline and on-treatment data at Week 24 were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 369 375 379 377 371 378
Least Squares Mean (Standard Error)
Unit of Measure: Liters
0.132  (0.0160) 0.220  (0.0159) 0.243  (0.0158) 0.168  (0.0159) 0.256  (0.0160) 0.286  (0.0158)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using Analysis of Covariance (ANCOVA) with covariates of treatment, age, sex, region, Baseline value, and pre-study ICS dosage at screening.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.088
Confidence Interval (2-Sided) 95%
0.044 to 0.132
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0226
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using ANCOVA with covariates of treatment, age, sex, region, Baseline value, and pre-study ICS dosage at screening.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.111
Confidence Interval (2-Sided) 95%
0.067 to 0.155
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0225
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using ANCOVA with covariates of treatment, age, sex, region, Baseline value, and pre-study ICS dosage at screening.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.088
Confidence Interval (2-Sided) 95%
0.044 to 0.132
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0225
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments p-value was calculated using ANCOVA with covariates of treatment, age, sex, region, Baseline value, and pre-study ICS dosage at screening.
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.118
Confidence Interval (2-Sided) 95%
0.074 to 0.162
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0224
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Mean Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) Total Score at Week 24
Hide Description The ACQ-7 consists of 7 attributes of asthma control, of which 6 to be self-completed by participant in a 6-item questionnaire, enquire about frequency and/or severity of symptoms over the previous week on: nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath, wheeze, and rescue medication use. The seventh attribute measures the lung function, which was included via pre-bronchodilator FEV1 % predicted value. All 7 items of ACQ have response on 0-6 ordinal scale (0=no impairment/limitation, 6=total impairment/limitation). The total score is calculated as the average of all non-missing item responses, ranges from 0 to 6. Higher score indicates worst symptoms. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was at randomization visit (pre-dose,Day 1). Change from Baseline was defined as value at Week 24 minus Baseline value.
Time Frame Baseline (pre-dose at Day 1) and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with available data at Baseline and at least one time point post-baseline were analyzed. Analysis used pooled data from two FF/UMEC/VI arms for each fixed UMEC dose compared to pooled data from two FF/VI arms to provide a more precise estimate for the treatment effect of the addition of UMEC to FF/VI.
Arm/Group Title FF/VI FF/UMEC/VI (UMEC 31.25 mcg) FF/UMEC/VI (UMEC 62.5 mcg)
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg or 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/31.25/25 mcg or 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/62.5/25 mcg or 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 784 784 790
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-0.678  (0.0240) -0.734  (0.0240) -0.767  (0.0238)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 31.25 mcg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.094
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.057
Confidence Interval (2-Sided) 95%
-0.124 to 0.010
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0340
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 62.5 mcg)
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.089
Confidence Interval (2-Sided) 95%
-0.156 to -0.023
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.0338
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Mean Change From Baseline in Saint George's Respiratory Questionnaire (SGRQ) Total Score at Week 24
Hide Description The SGRQ had 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure quality of life (QoL) of participants with airway obstruction, measuring symptoms, impact, and activity. The questions are designed to be self-completed by the participant with a recall over the past 3 months. SGRQ total score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100. SGRQ total score ranges from 0 to 100 where 0 indicates best and 100 indicates worst health. A change of 4 points is considered a clinically relevant change. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was at randomization visit (pre-dose at Day 1). Change from Baseline value is the value at Week 24 minus the Baseline value.
Time Frame Baseline (pre-dose at Day 1) and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with a Baseline value and at least one post-baseline measurement were analyzed. Analysis used pooled data from two FF/UMEC/VI arms for each fixed UMEC dose compared to pooled data from two FF/VI arms to provide a more precise estimate for the treatment effect of the addition of UMEC to FF/VI.
Arm/Group Title FF/VI FF/UMEC/VI (UMEC 31.25 mcg) FF/UMEC/VI (UMEC 62.5 mcg)
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg or 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/31.25/25 mcg or 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/62.5/25 mcg or 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 784 782 795
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-11.39  (0.491) -10.29  (0.494) -11.69  (0.487)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 31.25 mcg)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.115
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
-0.27 to 2.47
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.697
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 62.5 mcg)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.662
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.30
Confidence Interval (2-Sided) 95%
-1.66 to 1.05
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.692
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Mean Change From Baseline in Evaluating Respiratory Symptoms (E-RS) Total Score Over Weeks 21 to 24 (Inclusive) of the Treatment Period
Hide Description The E-RS in Chronic Obstructive Pulmonary Disease (COPD) consists of 11 items. E-RS captures information related to respiratory symptoms, i.e. breathlessness, cough, sputum production, chest congestion and chest tightness. The E-RS was completed daily and data was derived by 4-weekly intervals, requiring at least 50% of data to be present during a period. 7 items are scored from 0 (not at all) to 4 (extreme) and 4 items are scored from 0 (not at all) to 3 (extreme). The E-RS total score was calculated by taking sum of all the items. The E-RS total score has a scoring range of 0 to 40, with higher scores indicating more severe respiratory symptoms. Treatment policy estimand was assessed, including all on- and post-treatment data. Baseline value was the mean value of 14 days prior to randomization. Change from Baseline was calculated as post-baseline value (mean of daily E-RS total scores during Week 21 to 24 ) minus Baseline value.
Time Frame Baseline (14 days prior to randomization) and Weeks 21 to 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Participants with a Baseline value and at least one post-baseline measurement were analyzed. Analysis used pooled data from two FF/UMEC/VI arms for each fixed UMEC dose compared to pooled data from two FF/VI arms to provide a more precise estimate for the treatment effect of the addition of UMEC to FF/VI.
Arm/Group Title FF/VI FF/UMEC/VI (UMEC 31.25 mcg) FF/UMEC/VI (UMEC 62.5 mcg)
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg or 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/31.25/25 mcg or 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 100/62.5/25 mcg or 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 787 796 802
Least Squares Mean (Standard Error)
Unit of Measure: Scores on a scale
-2.47  (0.131) -2.60  (0.130) -2.89  (0.130)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 31.25 mcg)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.479
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and 4-weekly period, interaction terms for Baseline value by 4-weekly period and treatment by 4-weekly period.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.49 to 0.23
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.185
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI, FF/UMEC/VI (UMEC 62.5 mcg)
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.023
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and 4-weekly period, interaction terms for Baseline value by 4-weekly period and treatment by 4-weekly period.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.42
Confidence Interval (2-Sided) 95%
-0.78 to -0.06
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.184
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Any Serious Adverse Event (SAE) and Common (>=3%) Non-SAE
Hide Description Adverse event (AE) is any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, events associated with liver injury and impaired liver function, or any other situation according to medical or scientific judgment were categorized as SAE. Number of participants with any SAE and common (>=3%) non-SAEs are presented.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 407 405 406 406 404 408
Measure Type: Count of Participants
Unit of Measure: Participants
Common non-SAE
136
  33.4%
150
  37.0%
135
  33.3%
122
  30.0%
127
  31.4%
122
  29.9%
SAE
25
   6.1%
18
   4.4%
23
   5.7%
21
   5.2%
23
   5.7%
21
   5.1%
8.Secondary Outcome
Title Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Hide Description Twelve-lead ECGs were performed during the study using an automated ECG machine. All ECG measurements were made with the participant in a supine position having rested in this position for approximately 5 minutes before each reading. The number of participants with worst case post-Baseline abnormal ECG findings were reported.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time point were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 401 398 398 397 399 404
Measure Type: Count of Participants
Unit of Measure: Participants
115
  28.7%
118
  29.6%
109
  27.4%
109
  27.5%
106
  26.6%
108
  26.7%
9.Secondary Outcome
Title Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Week 24
Hide Description Blood pressure (systolic and diastolic) was measured in the sitting position after approximately 5 minutes rest. Baseline value is the last acceptable/borderline acceptable value prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at the clinic visit minus the Baseline value. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement.
Time Frame Baseline (pre-dose at Day 1) and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data point were analyzed. Participants with a Baseline value and at least one post-baseline measurement were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 401 398 399 397 399 402
Least Squares Mean (Standard Error)
Unit of Measure: Millimeter of mercury
SBP 1.6  (0.53) 0.6  (0.53) 1.1  (0.52) 0.2  (0.53) 0.8  (0.53) 0.9  (0.52)
DBP 0.4  (0.39) 0.1  (0.39) 1.3  (0.39) 0.4  (0.39) 0.2  (0.40) 0.8  (0.39)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.172
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-2.5 to 0.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.75
Estimation Comments Comparison for SBP
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.436
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-2.0 to 0.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.74
Estimation Comments Comparison for SBP
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.426
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.6
Confidence Interval (2-Sided) 95%
-0.9 to 2.1
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.75
Estimation Comments Comparison for SBP
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-0.8 to 2.2
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.74
Estimation Comments Comparison for SBP
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.482
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-1.5 to 0.7
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments Comparison for DBP
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.142
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.8
Confidence Interval (2-Sided) 95%
-0.3 to 1.9
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments Comparison for DBP
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.806
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.1
Confidence Interval (2-Sided) 95%
-1.2 to 1.0
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.56
Estimation Comments Comparison for DBP
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.447
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.4
Confidence Interval (2-Sided) 95%
-0.7 to 1.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.55
Estimation Comments Comparison for DBP
10.Secondary Outcome
Title Mean Change From Baseline in Pulse Rate at Week 24
Hide Description Pulse Rate was measured in the sitting position after approximately 5 minutes rest. Baseline value is the last acceptable/borderline acceptable value prior to randomized treatment start date (pre-dose at Day 1). Change from Baseline value is the value at the clinic visit minus the Baseline value. Different participants may have been analyzed at different time points; thus, overall number of participants analyzed reflects everyone in ITT Population without missing covariate information, with Baseline and at least one post-baseline measurement.
Time Frame Baseline (pre-dose at Day 1) and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified data point were analyzed. Participants with a Baseline value and at least one post-baseline measurement were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 401 398 399 397 399 402
Least Squares Mean (Standard Error)
Unit of Measure: Beats per minute
-1.1  (0.43) 0.2  (0.43) -1.0  (0.43) -0.7  (0.43) -1.3  (0.44) -0.5  (0.43)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.034
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 1.3
Confidence Interval (2-Sided) 95%
0.1 to 2.5
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg, FF/UMEC/VI 100/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.839
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.1
Confidence Interval (2-Sided) 95%
-1.1 to 1.3
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/ 31.25/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.349
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 0.6
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection FF/VI 200/25 mcg, FF/UMEC/VI 200/62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.768
Comments p-value was calculated using MMRM with covariates of treatment, age, sex, region, Baseline value, pre-study ICS dosage at screening, and visit, interaction terms for Baseline value by visit and treatment by visit.
Method Mixed Model Repeated Measures
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-1.0 to 1.4
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.61
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Number of Participants With Abnormal Clinical Chemistry Values
Hide Description Blood samples were collected for assessment of clinical chemistry parameters, which included albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), direct bilirubin, total bilirubin, calcium, creatinine, glucose, potassium, protein, sodium and urea. Abnormal laboratory results are categorized as high or low with respect to their normal ranges. Participants having High and Low values from normal ranges for any parameter at any time post-baseline visits are presented.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time point were analyzed.
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 391 392 394 390 391 397
Measure Type: Count of Participants
Unit of Measure: Participants
Albumin, low
2
   0.5%
0
   0.0%
0
   0.0%
1
   0.3%
0
   0.0%
0
   0.0%
Albumin, high
1
   0.3%
6
   1.5%
5
   1.3%
2
   0.5%
3
   0.8%
1
   0.3%
ALT, low
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
ALT, high
41
  10.5%
29
   7.4%
24
   6.1%
28
   7.2%
27
   6.9%
30
   7.6%
AST, low
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
AST, high
29
   7.4%
27
   6.9%
14
   3.6%
21
   5.4%
23
   5.9%
16
   4.0%
ALP, low
1
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.3%
0
   0.0%
ALP, high
21
   5.4%
15
   3.8%
10
   2.5%
12
   3.1%
16
   4.1%
12
   3.0%
Direct bilirubin, low
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Direct bilirubin, high
1
   0.3%
1
   0.3%
0
   0.0%
2
   0.5%
2
   0.5%
1
   0.3%
Bilirubin, low
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Bilirubin, high
9
   2.3%
12
   3.1%
5
   1.3%
15
   3.8%
17
   4.3%
13
   3.3%
Calcium, low
4
   1.0%
9
   2.3%
7
   1.8%
7
   1.8%
4
   1.0%
3
   0.8%
Calcium, high
4
   1.0%
12
   3.1%
10
   2.5%
11
   2.8%
8
   2.0%
7
   1.8%
Creatinine, low
54
  13.8%
62
  15.8%
49
  12.4%
63
  16.2%
60
  15.3%
64
  16.1%
Creatinine, high
7
   1.8%
7
   1.8%
8
   2.0%
6
   1.5%
9
   2.3%
8
   2.0%
Glucose, low
15
   3.8%
11
   2.8%
11
   2.8%
7
   1.8%
12
   3.1%
7
   1.8%
Glucose, high
74
  18.9%
71
  18.1%
70
  17.8%
76
  19.5%
66
  16.9%
73
  18.4%
Potassium, low
2
   0.5%
3
   0.8%
1
   0.3%
7
   1.8%
7
   1.8%
6
   1.5%
Potassium, high
15
   3.8%
13
   3.3%
11
   2.8%
9
   2.3%
12
   3.1%
19
   4.8%
Protein, low
3
   0.8%
0
   0.0%
5
   1.3%
3
   0.8%
1
   0.3%
2
   0.5%
Protein, high
0
   0.0%
1
   0.3%
3
   0.8%
2
   0.5%
3
   0.8%
1
   0.3%
Sodium, low
5
   1.3%
7
   1.8%
3
   0.8%
5
   1.3%
7
   1.8%
3
   0.8%
Sodium, high
6
   1.5%
7
   1.8%
7
   1.8%
4
   1.0%
5
   1.3%
7
   1.8%
Urea, low
3
   0.8%
4
   1.0%
5
   1.3%
3
   0.8%
3
   0.8%
1
   0.3%
Urea, high
13
   3.3%
17
   4.3%
3
   0.8%
11
   2.8%
11
   2.8%
13
   3.3%
12.Secondary Outcome
Title Number of Participants With Abnormal Hematology Values
Hide Description Blood samples were collected for assessment of hematology parameters, which included Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, Erythrocytes, Hematocrit, Hemoglobin, Leukocytes, Platelets, Mean Corpuscular Hemoglobin (MCH) and Mean Corpuscular Volume (MCV). Abnormal laboratory results are categorized as high or low with respect to their normal ranges. Participants having High and Low values from normal ranges for any parameter at any time post-baseline visits are presented.
Time Frame Up to Week 52
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population. Only those participants with data available at the specified time point were analyzed (represented by n=X in category titles).
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description:
Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period
Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
Overall Number of Participants Analyzed 391 390 392 391 391 397
Measure Type: Count of Participants
Unit of Measure: Participants
Basophils, low, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Basophils, high, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
1
   0.3%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Eosinophils, low, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
26
   6.7%
27
   6.9%
25
   6.4%
31
   8.0%
32
   8.2%
28
   7.1%
Eosinophils, high, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
111
  28.5%
84
  21.5%
102
  26.1%
84
  21.6%
85
  21.9%
78
  19.7%
Lymphocytes, low, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
13
   3.3%
11
   2.8%
13
   3.3%
8
   2.1%
13
   3.3%
10
   2.5%
Lymphocytes, high, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
2
   0.5%
5
   1.3%
1
   0.3%
7
   1.8%
6
   1.5%
6
   1.5%
Monocytes, low, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
60
  15.4%
68
  17.4%
57
  14.6%
64
  16.5%
51
  13.1%
63
  15.9%
Monocytes, high, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
7
   1.8%
1
   0.3%
4
   1.0%
2
   0.5%
7
   1.8%
4
   1.0%
Neutrophils, low, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
14
   3.6%
10
   2.6%
16
   4.1%
10
   2.6%
12
   3.1%
9
   2.3%
Neutrophils, high, n=390,390,391,389,389,396 Number Analyzed 390 participants 390 participants 391 participants 389 participants 389 participants 396 participants
21
   5.4%
20
   5.1%
15
   3.8%
19
   4.9%
15
   3.9%
34
   8.6%
Erythrocytes, low, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
14
   3.6%
16
   4.1%
11
   2.8%
15
   3.8%
21
   5.4%
22
   5.5%
Erythrocytes, high, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
24
   6.1%
21
   5.4%
13
   3.3%
12
   3.1%
17
   4.3%
17
   4.3%
Hematocrit, low, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
21
   5.4%
28
   7.2%
16
   4.1%
20
   5.1%
20
   5.1%
26
   6.5%
Hematocrit, high, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
60
  15.3%
52
  13.3%
50
  12.8%
47
  12.0%
49
  12.5%
49
  12.3%
Hemoglobin, low, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
32
   8.2%
47
  12.1%
40
  10.2%
40
  10.2%
37
   9.5%
34
   8.6%
Hemoglobin, high, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
14
   3.6%
13
   3.3%
8
   2.0%
17
   4.3%
10
   2.6%
13
   3.3%
Leukocytes, low, n=391,390,391,389,391,396 Number Analyzed 391 participants 390 participants 391 participants 389 participants 391 participants 396 participants
9
   2.3%
12
   3.1%
14
   3.6%
9
   2.3%
12
   3.1%
8
   2.0%
Leukocytes, high, n=391,390,391,389,391,396 Number Analyzed 391 participants 390 participants 391 participants 389 participants 391 participants 396 participants
38
   9.7%
29
   7.4%
20
   5.1%
31
   8.0%
26
   6.6%
40
  10.1%
Platelets, low, n=391,388,389,391,388,396 Number Analyzed 391 participants 388 participants 389 participants 391 participants 388 participants 396 participants
4
   1.0%
2
   0.5%
3
   0.8%
4
   1.0%
5
   1.3%
4
   1.0%
Platelets, high, n=391,388,389,391,388,396 Number Analyzed 391 participants 388 participants 389 participants 391 participants 388 participants 396 participants
17
   4.3%
16
   4.1%
19
   4.9%
21
   5.4%
19
   4.9%
21
   5.3%
MCH, low, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
40
  10.2%
47
  12.1%
24
   6.1%
34
   8.7%
41
  10.5%
25
   6.3%
MCH, high, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
18
   4.6%
32
   8.2%
22
   5.6%
17
   4.3%
25
   6.4%
32
   8.1%
MCV, low, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
20
   5.1%
22
   5.6%
10
   2.6%
15
   3.8%
19
   4.9%
14
   3.5%
MCV, high, n=391,390,392,391,391,397 Number Analyzed 391 participants 390 participants 392 participants 391 participants 391 participants 397 participants
29
   7.4%
41
  10.5%
25
   6.4%
29
   7.4%
26
   6.6%
37
   9.3%
Time Frame Non-serious AEs and serious AEs were collected from start of study treatment (Week 0) up to Week 52
Adverse Event Reporting Description Non-serious AEs and serious AEs were collected for ITT Population.
 
Arm/Group Title FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Hide Arm/Group Description Participants received Fluticasone Furoate/ Vilanterol (FF/VI) 100/25 micrograms (mcg) inhalation powder via dry powder inhaler (DPI), once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received Fluticasone Furoate/Umeclidinium/Vilanterol (FF/UMEC/VI) 100/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 100/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/VI 200/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/31.25/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period. Participants received FF/UMEC/VI 200/62.5/25 mcg inhalation powder via DPI, once daily in the morning up to 52 weeks. Participants were allowed to take albuterol/salbutamol as a rescue medication when needed during the treatment period.
All-Cause Mortality
FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/407 (0.00%)   2/405 (0.49%)   0/406 (0.00%)   1/406 (0.25%)   0/404 (0.00%)   0/408 (0.00%) 
Hide Serious Adverse Events
FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   25/407 (6.14%)   18/405 (4.44%)   23/406 (5.67%)   21/406 (5.17%)   23/404 (5.69%)   21/408 (5.15%) 
Cardiac disorders             
Angina unstable † 1  2/407 (0.49%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Myocardial infarction † 1  0/407 (0.00%)  0/405 (0.00%)  2/406 (0.49%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Acute coronary syndrome † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Acute myocardial infarction † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Angina pectoris † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Atrial fibrillation † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Atrial flutter † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Congenital, familial and genetic disorders             
Hypertrophic cardiomyopathy † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Eye disorders             
Retinal detachment † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Gastrointestinal disorders             
Pancreatitis † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Abdominal pain † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Chronic gastritis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Colitis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Colitis ulcerative † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Gastrointestinal ulcer haemorrhage † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Hiatus hernia † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Intestinal haemorrhage † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Intestinal obstruction † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Irritable bowel syndrome † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Pancreatitis acute † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Hepatobiliary disorders             
Cholecystitis acute † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  1/408 (0.25%) 
Immune system disorders             
Anaphylactic reaction † 1  0/407 (0.00%)  1/405 (0.25%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Infections and infestations             
Pneumonia † 1  2/407 (0.49%)  0/405 (0.00%)  3/406 (0.74%)  3/406 (0.74%)  4/404 (0.99%)  1/408 (0.25%) 
Pneumonia bacterial † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Acute sinusitis † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Anal abscess † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Bronchitis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Cellulitis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Chronic sinusitis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Diverticulitis † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Metapneumovirus infection † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Periodontitis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Pneumonia influenzal † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Respiratory tract infection † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Sepsis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Soft tissue infection † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Viral upper respiratory tract infection † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Wound sepsis † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Injury, poisoning and procedural complications             
Ankle fracture † 1  1/407 (0.25%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Limb injury † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Clavicle fracture † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Facial bones fracture † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Hip fracture † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Jaw fracture † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Joint injury † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Ligament sprain † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Musculoskeletal foreign body † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Pulmonary contusion † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Rib fracture † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Spinal compression fracture † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Investigations             
Hepatic enzyme increased † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Metabolism and nutrition disorders             
Diabetes mellitus inadequate control † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Hyperglycaemia † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Musculoskeletal and connective tissue disorders             
Foot deformity † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Osteoarthritis † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Polymyalgia rheumatica † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Spinal disorder † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Trigger finger † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)             
Prostate cancer † 1  1/407 (0.25%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Adenocarcinoma of colon † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Bladder cancer † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Breast cancer † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Endometrial cancer † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Intestinal adenocarcinoma † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Lip and/or oral cavity cancer † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Lung adenocarcinoma † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Pancreatic carcinoma † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Rectal cancer † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Tumour haemorrhage † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  1/404 (0.25%)  0/408 (0.00%) 
Nervous system disorders             
Cerebrovascular disorder † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Facial paralysis † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Haemorrhagic stroke † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Hypertensive encephalopathy † 1  0/407 (0.00%)  0/405 (0.00%)  1/406 (0.25%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Sciatica † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Renal and urinary disorders             
Nephrolithiasis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Nephropathy toxic † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Stress urinary incontinence † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Reproductive system and breast disorders             
Endometrial hyperplasia † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Uterine haemorrhage † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Respiratory, thoracic and mediastinal disorders             
Asthma † 1  7/407 (1.72%)  7/405 (1.73%)  7/406 (1.72%)  6/406 (1.48%)  5/404 (1.24%)  4/408 (0.98%) 
Nasal polyps † 1  0/407 (0.00%)  0/405 (0.00%)  2/406 (0.49%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Pulmonary embolism † 1  0/407 (0.00%)  1/405 (0.25%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  2/408 (0.49%) 
Chronic rhinosinusitis with nasal polyps † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Status asthmaticus † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
Skin and subcutaneous tissue disorders             
Urticaria † 1  1/407 (0.25%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  0/408 (0.00%) 
Vascular disorders             
Circulatory collapse † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  1/406 (0.25%)  0/404 (0.00%)  0/408 (0.00%) 
Hypertensive crisis † 1  0/407 (0.00%)  0/405 (0.00%)  0/406 (0.00%)  0/406 (0.00%)  0/404 (0.00%)  1/408 (0.25%) 
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
FF/VI 100/25 mcg FF/UMEC/VI 100/ 31.25/25 mcg FF/UMEC/VI 100/62.5/25 mcg FF/VI 200/25 mcg FF/UMEC/VI 200/ 31.25/25 mcg FF/UMEC/VI 200/62.5/25 mcg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   136/407 (33.42%)   150/405 (37.04%)   135/406 (33.25%)   122/406 (30.05%)   127/404 (31.44%)   122/408 (29.90%) 
Infections and infestations             
Nasopharyngitis † 1  63/407 (15.48%)  56/405 (13.83%)  60/406 (14.78%)  53/406 (13.05%)  51/404 (12.62%)  51/408 (12.50%) 
Upper respiratory tract infection † 1  21/407 (5.16%)  24/405 (5.93%)  15/406 (3.69%)  13/406 (3.20%)  15/404 (3.71%)  19/408 (4.66%) 
Bronchitis † 1  14/407 (3.44%)  18/405 (4.44%)  15/406 (3.69%)  19/406 (4.68%)  16/404 (3.96%)  22/408 (5.39%) 
Respiratory tract infection viral † 1  11/407 (2.70%)  17/405 (4.20%)  10/406 (2.46%)  7/406 (1.72%)  12/404 (2.97%)  9/408 (2.21%) 
Influenza † 1  13/407 (3.19%)  12/405 (2.96%)  15/406 (3.69%)  9/406 (2.22%)  8/404 (1.98%)  6/408 (1.47%) 
Pharyngitis † 1  8/407 (1.97%)  10/405 (2.47%)  9/406 (2.22%)  14/406 (3.45%)  11/404 (2.72%)  9/408 (2.21%) 
Musculoskeletal and connective tissue disorders             
Back pain † 1  16/407 (3.93%)  12/405 (2.96%)  13/406 (3.20%)  6/406 (1.48%)  14/404 (3.47%)  9/408 (2.21%) 
Nervous system disorders             
Headache † 1  30/407 (7.37%)  31/405 (7.65%)  36/406 (8.87%)  23/406 (5.67%)  27/404 (6.68%)  19/408 (4.66%) 
1
Term from vocabulary, MedDRA 21.1
†
Indicates events were collected by systematic assessment
[Not Specified]
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
EMail: GSKClinicalSupportHD@gsk.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02924688    
Other Study ID Numbers: 205715
2016-001304-37 ( EudraCT Number )
First Submitted: September 12, 2016
First Posted: October 5, 2016
Results First Submitted: February 4, 2020
Results First Posted: February 21, 2020
Last Update Posted: March 26, 2021