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An Efficacy and Safety Study of Fluticasone Furoate/Vilanterol 100/25 Microgram (mcg) Inhalation Powder, Fluticasone Propionate/Salmeterol 250/50 mcg Inhalation Powder, and Fluticasone Propionate 250 mcg Inhalation Powder in Adults and Adolescents With Persistent Asthma

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ClinicalTrials.gov Identifier: NCT02301975
Recruitment Status : Completed
First Posted : November 26, 2014
Results First Posted : June 12, 2017
Last Update Posted : August 6, 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/Vilanterol 100/25 mcg via ELLIPTA inhaler
Drug: Placebo inhalation powders via ELLIPTA inhaler
Drug: Fluticasone Propionate/Salmeterol 250/50 mcg via ACCUHALER/DISKUS inhaler
Drug: Placebo inhalation powder via ACCUHALER/DISKUS inhaler
Drug: Fluticasone Propionate 250 mcg via ACCUHALER/DISKUS inhaler
Enrollment 1526
Recruitment Details Eligible participants at screening and run-in visits entered a 24 Week treatment period and were randomized to receive either Fluticasone furoate/Vilanterol (FF/VI) 100/25 micrograms (mcg) or Fluticasone propionate/salmeterol (FP/S) 250/50mcg or only FP 250mcg followed by a follow-up phase. The total duration for study participation was 30 weeks.
Pre-assignment Details A total of 3162 adult and adolescent participants with asthma were screened, out of which 516 were screen-failures, 1124 were run-in failures, 1522 participants were randomized, and 1504 subjects received at least one dose of study medication to be included in the Intent-to-Treat (ITT) Population.
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Period Title: Overall Study
Started 504 501 499
Completed 473 476 477
Not Completed 31 25 22
Reason Not Completed
Adverse Event             8             3             2
Lack of Efficacy             1             1             1
Protocol Violation             3             5             3
Lost to Follow-up             0             2             2
Physician Decision             4             2             3
Withdrawal by Subject             15             12             11
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily Total
Hide Arm/Group Description Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Total of all reporting groups
Overall Number of Baseline Participants 504 501 499 1504
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Participants
Number Analyzed 504 participants 501 participants 499 participants 1504 participants
44.4  (16.30) 43.0  (15.20) 43.0  (16.58) 43.5  (16.04)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 504 participants 501 participants 499 participants 1504 participants
Female
314
  62.3%
336
  67.1%
314
  62.9%
964
  64.1%
Male
190
  37.7%
165
  32.9%
185
  37.1%
540
  35.9%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 504 participants 501 participants 499 participants 1504 participants
American Indian or Alaska native 0 0 1 1
Asian - East Asian Heritage 8 11 4 23
Asian- Japanese Heritage 1 0 0 1
Asian- South East Asian Heritage 1 0 1 2
Black/African American Heritage 12 14 17 43
White- Arabic/ North African Heritage 0 1 2 3
White- White/Caucasian/European Heritage 415 407 410 1232
White- Mixed White Race 1 0 0 1
African American/ African and White Heritage 0 5 0 5
American Indian/Alaskan Native and White Heritage 66 62 64 192
Asian - East Asian and White Heritage 0 1 0 1
1.Primary Outcome
Title Change From Baseline in Evening (Post Meridiem [PM]) Forced Expiratory Volume in One Second (FEV1) Using Intent-to-Treat (ITT) Population
Hide Description FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the mixed model repeated measures (MMRM) model and least square mean and standard error were calculated. The analysis was performed on ITT Population which comprised of all participants randomized to treatment and who received at least one dose of study medication.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 487 487 479
Least Squares Mean (Standard Error)
Unit of Measure: Liter (L)
0.019  (0.0107) 0.000  (0.0108) -0.104  (0.0109)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit PM FEV1 for FF/VI and FP/S was more than -100 milliliter (mL)
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.019
Confidence Interval (2-Sided) 95%
-0.011 to 0.049
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.123
Confidence Interval (2-Sided) 95%
0.093 to 0.153
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.104
Confidence Interval (2-Sided) 95%
0.074 to 0.134
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline in PM FEV1 Using Per Protocol (PP) Population
Hide Description FEV1 was defined as the volume of air that can be forced out in one second after taking a deep breath. FEV1 (pre-bronchodilator and pre-dose) was measured at Baseline up to Week 24 at evening using spirometry. Repeated Measures analysis was adjusted for Baseline, region, sex, age, treatment, visit, visit by Baseline interaction and visit by treatment interaction. Visit 3 values were taken as Baseline value and change from Baseline was defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Statistical analysis was performed using the MMRM models and least square mean and standard error were calculated. The analysis was performed on PP Population which comprised of all participants in the ITT Population who did not had any full protocol deviations.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
PP Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 425 426 419
Least Squares Mean (Standard Error)
Unit of Measure: L
0.020  (0.0120) 0.014  (0.0120) -0.099  (0.0121)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments Non-inferiority was defined if the lower bound of the 95% CI for the difference between mean change from Baseline in clinic visit for FF/VI and FP/S was more than -100 mL
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.006
Confidence Interval (2-Sided) 95%
-0.027 to 0.040
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.120
Confidence Interval (2-Sided) 95%
0.086 to 0.153
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 0.113
Confidence Interval (2-Sided) 95%
0.080 to 0.147
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in the Percentage of Rescue-free 24-hour Periods
Hide Description The number of inhalations of rescue medication used during the day and night were recorded by participants using an electronic diary (e-diary). A 24-hour (hr) period in which a participant’s responses to both the morning and evening assessments indicated no use of rescue medication was considered to be rescue free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Time Frame Baseline and Weeks 1-24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 500 498 496
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of rescue-free 24-hr periods
-3.0  (0.62) -4.2  (0.62) -5.7  (0.62)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.5 to 3.0
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.002
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
0.9 to 4.4
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.106
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-0.3 to 3.2
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Change From Baseline in the Percentage of Symptom-free 24-hour Periods
Hide Description Change from Baseline in the percentage of symptom-free 24 hour period was evaluated. A 24-hour (hr) period in which a participant’s responses to both the morning and evening assessments indicated no symptoms was considered to be symptom free. The Baseline value was derived from the last 7 days of the daily eDiary prior to the randomization of the participant. Change from Baseline was calculated as the averaged value during the 24-week treatment period minus the Baseline value.Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Time Frame Baseline and Weeks 1-24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 500 498 496
Least Squares Mean (Standard Error)
Unit of Measure: Percentage of symptom-free 24 hour perio
-3.5  (0.67) -4.7  (0.67) -6.2  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-0.7 to 3.1
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 2.7
Confidence Interval (2-Sided) 95%
0.8 to 4.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.115
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 1.5
Confidence Interval (2-Sided) 95%
-0.4 to 3.3
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Morning (Ante Meridiem [AM]) Peak Expiratory Flow (PEF)
Hide Description PEF was measured using an electric flow meter each morning. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily AM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Time Frame Baseline and Weeks 1-24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 501 499 497
Least Squares Mean (Standard Error)
Unit of Measure: Liter per minute (L/min)
8.9  (1.48) 3.7  (1.49) -12.6  (1.49)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 5.2
Confidence Interval (2-Sided) 95%
1.1 to 9.4
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test 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 Least square mean change difference
Estimated Value 21.5
Confidence Interval (2-Sided) 95%
17.4 to 25.6
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test 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 Least square mean change difference
Estimated Value 16.3
Confidence Interval (2-Sided) 95%
12.2 to 20.4
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants With Asthma Control Test (ACT) Score Greater Than or Equal to 20
Hide Description The ACT was a five-item questionnaire developed as a measure of participant’s asthma control. The percentage of participants controlled, defined as having ACT score greater than or equal to 20 at the end of Week 24 were analyzed using logistic regression model with covariates of Baseline ACT score, region, sex, age and treatment group.
Time Frame Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 471 467 461
Measure Type: Number
Unit of Measure: Percentage of participants
92 93 91
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.91
Confidence Interval (2-Sided) 95%
0.53 to 1.54
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.595
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.15
Confidence Interval (2-Sided) 95%
0.69 to 1.90
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.372
Comments [Not Specified]
Method Regression, Logistic
Comments [Not Specified]
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.75 to 2.12
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Change From Baseline in PM PEF
Hide Description PEF was measured using an electric flow meter each evening. Change from Baseline (defined as the last 7 days prior to randomization of the participants) was calculated as the value of the averaged daily PM PEF over the 24-week treatment period minus the Baseline value. Statistical analysis was performed using an ANCOVA model with covariates of Baseline, region, sex, age and treatment and least square mean and standard error were calculated.
Time Frame Baseline and Weeks 1-24
Hide Outcome Measure Data
Hide Analysis Population Description
ITT Population
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description:
Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
Overall Number of Participants Analyzed 501 498 496
Least Squares Mean (Standard Error)
Unit of Measure: L/min
5.5  (1.55) 0.5  (1.55) -13.7  (1.55)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP/S 250/50 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square mean change difference
Estimated Value 5.0
Confidence Interval (2-Sided) 95%
0.7 to 9.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection FF/VI 100/25 mcg Once Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test 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 Least square mean change difference
Estimated Value 19.2
Confidence Interval (2-Sided) 95%
14.9 to 23.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection FP/S 250/50 mcg Twice Daily, FP 250 mcg Twice Daily
Comments [Not Specified]
Type of Statistical Test 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 Least square mean change difference
Estimated Value 14.2
Confidence Interval (2-Sided) 95%
9.9 to 18.5
Estimation Comments [Not Specified]
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study treatment until the follow up contact one week after completion of study medication (Up to Week 25).
Adverse Event Reporting Description AEs and SAEs were collected in ITT Population
 
Arm/Group Title FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Hide Arm/Group Description Participants received FF/VI 100/25 mcg via ELLIPTA® inhaler once daily (at evening) along with placebo via ACCUHALER/DISKUS® twice daily for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP/S 250/50 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms. Participants received FP 250 mcg via ACCUHALER/DISKUS inhaler twice daily along with placebo via ELLIPTA inhaler once daily (at evening) for 24 weeks. Albuterol/Salbutamol inhalation aerosol was also provided to treat acute asthma symptoms.
All-Cause Mortality
FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/504 (0.00%)   0/501 (0.00%)   0/499 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   6/504 (1.19%)   4/501 (0.80%)   5/499 (1.00%) 
Gastrointestinal disorders       
Large intestine perforation  1  0/504 (0.00%)  1/501 (0.20%)  0/499 (0.00%) 
Hepatobiliary disorders       
Cholecystitis acute  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
Infections and infestations       
Abdominal abscess  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
Pneumonia  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Injury, poisoning and procedural complications       
Ankle fracture  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Foot fracture  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
Musculoskeletal and connective tissue disorders       
Intervertebral disc protrusion  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Joint instability  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
Osteoarthritis  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
Synovial cyst  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Invasive lobular breast carcinoma  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Nervous system disorders       
Epilepsy  1  0/504 (0.00%)  1/501 (0.20%)  0/499 (0.00%) 
Psychiatric disorders       
Psychotic disorder  1  0/504 (0.00%)  1/501 (0.20%)  0/499 (0.00%) 
Renal and urinary disorders       
Renal colic  1  1/504 (0.20%)  0/501 (0.00%)  0/499 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
Vocal cord leukoplakia  1  0/504 (0.00%)  1/501 (0.20%)  0/499 (0.00%) 
Vascular disorders       
Hypertension  1  0/504 (0.00%)  0/501 (0.00%)  1/499 (0.20%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
FF/VI 100/25 mcg Once Daily FP/S 250/50 mcg Twice Daily FP 250 mcg Twice Daily
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   126/504 (25.00%)   123/501 (24.55%)   124/499 (24.85%) 
Infections and infestations       
Bronchitis  1  20/504 (3.97%)  10/501 (2.00%)  13/499 (2.61%) 
Influenza  1  9/504 (1.79%)  12/501 (2.40%)  19/499 (3.81%) 
Nasopharyngitis  1  61/504 (12.10%)  67/501 (13.37%)  57/499 (11.42%) 
Pharyngitis  1  15/504 (2.98%)  13/501 (2.59%)  18/499 (3.61%) 
Nervous system disorders       
Headache  1  41/504 (8.13%)  37/501 (7.39%)  40/499 (8.02%) 
1
Term from vocabulary, MedDRA 19.1
Indicates events were collected by systematic assessment
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: NCT02301975     History of Changes
Other Study ID Numbers: 201378
First Submitted: November 24, 2014
First Posted: November 26, 2014
Results First Submitted: May 8, 2017
Results First Posted: June 12, 2017
Last Update Posted: August 6, 2018