Trial Outcomes & Findings for Crossover Study Comparing Fluticasone Furoate (FF)/Vilanterol (VI) Once Daily Versus Fluticasone Propionate (FP) Twice Daily in Subjects With Asthma and Exercise-Induced Bronchoconstriction (EIB) (NCT NCT02730351)
NCT ID: NCT02730351
Last Updated: 2019-07-16
Results Overview
The exercise challenge test is a stepped challenge on a treadmill. It was performed at 12 hrs post evening dose at the end of the 2-week treatment period, wherein the participants exercised sufficiently to reach a heart rate between 80 to 95 percent of their predicted maximum within 4 minutes (min) and maintained the heart rate with exercise for an additional 6 min followed immediately by serial assessments of FEV1 at 5, 10, 15, 30, 45 and 60 min post-exercise. Maximal percent decrease was calculated as pre-exercise FEV1 minus minimum post exercise FEV1 (smallest FEV1 value collected within one hr following exercise challenge) divided by pre-exercise FEV1 multiplied by 100. Pre-exercise FEV1 was defined as the FEV1 collected prior to the exercise challenge test at 12 hr post dose. ITT Population comprised of all participants randomized to treatment and who received at least one dose of study medication.
COMPLETED
PHASE4
75 participants
At Week 2 of treatment period 1 and 2
2019-07-16
Participant Flow
This was a multicenter, randomized, double-blind, double-dummy, crossover comparison study of fluticasone furoate (FF)/vilanterol (VI) versus fluticasone propionate (FP) in adolescent and adult participants with asthma and exercise-induced bronchoconstriction (EIB). The study was conducted in two countries-United States and Canada.
The study consisted of 4-week single-blind run-in, 2-week double-blind treatment period 1, 2-week single-blind wash out, 2-week double-blind treatment period 2 and 1-week Follow-up. A total of 163 participants were screened, 75 were randomized and 74 were included in Intent-To-Treat (ITT) Population who received at least 1 dose of trial medication.
Participant milestones
| Measure |
FF/VI 100/25 µg Followed by FP 250 µg
After screening, the eligible participants entered a 4-week single blind run-in period on FP 250 microgram (µg) twice daily (BID) following which the participants were randomized to receive FF/VI 100/25 µg once daily (QD) via ELLIPTA + Placebo BID via DISKUS in treatment period 1 followed by a 2-week single blind wash-out period on FP 250 µg BID. The participants then received FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 2. The participants were followed up for approximately 7 days after completing Treatment Period 2. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg Followed by FF/VI 100/25 µg
After screening, the eligible participants entered a 4-week single blind run-in period on FP 250 µg BID following which the participants were randomized to receive FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 1 followed by a 2-week single blind wash-out period on FP 250 µg BID. The participants then received FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in treatment period 2. The participants were followed up for approximately 7 days after completing Treatment Period 2. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Treatment Period 1 (2 Weeks)
STARTED
|
37
|
37
|
|
Treatment Period 1 (2 Weeks)
COMPLETED
|
36
|
37
|
|
Treatment Period 1 (2 Weeks)
NOT COMPLETED
|
1
|
0
|
|
Wash-out Period (2 Weeks)
STARTED
|
36
|
37
|
|
Wash-out Period (2 Weeks)
COMPLETED
|
35
|
36
|
|
Wash-out Period (2 Weeks)
NOT COMPLETED
|
1
|
1
|
|
Treatment Period 2 (2 Weeks)
STARTED
|
35
|
36
|
|
Treatment Period 2 (2 Weeks)
COMPLETED
|
33
|
36
|
|
Treatment Period 2 (2 Weeks)
NOT COMPLETED
|
2
|
0
|
Reasons for withdrawal
| Measure |
FF/VI 100/25 µg Followed by FP 250 µg
After screening, the eligible participants entered a 4-week single blind run-in period on FP 250 microgram (µg) twice daily (BID) following which the participants were randomized to receive FF/VI 100/25 µg once daily (QD) via ELLIPTA + Placebo BID via DISKUS in treatment period 1 followed by a 2-week single blind wash-out period on FP 250 µg BID. The participants then received FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 2. The participants were followed up for approximately 7 days after completing Treatment Period 2. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg Followed by FF/VI 100/25 µg
After screening, the eligible participants entered a 4-week single blind run-in period on FP 250 µg BID following which the participants were randomized to receive FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 1 followed by a 2-week single blind wash-out period on FP 250 µg BID. The participants then received FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in treatment period 2. The participants were followed up for approximately 7 days after completing Treatment Period 2. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Treatment Period 1 (2 Weeks)
Adverse Event
|
1
|
0
|
|
Wash-out Period (2 Weeks)
Protocol Violation
|
0
|
1
|
|
Wash-out Period (2 Weeks)
Withdrawal by Subject
|
1
|
0
|
|
Treatment Period 2 (2 Weeks)
Adverse Event
|
1
|
0
|
|
Treatment Period 2 (2 Weeks)
Lack of Efficacy
|
1
|
0
|
Baseline Characteristics
Crossover Study Comparing Fluticasone Furoate (FF)/Vilanterol (VI) Once Daily Versus Fluticasone Propionate (FP) Twice Daily in Subjects With Asthma and Exercise-Induced Bronchoconstriction (EIB)
Baseline characteristics by cohort
| Measure |
All Treatment Combined
n=74 Participants
After screening, the eligible participants entered a 4-week single blind run-in period on FP 250 µg BID following which the participants were randomized to one of the following two treatment sequences in a ratio of 1:1: FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in treatment period 1 followed by FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 2 or FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in treatment period 1 followed by FF/VI 100/25 µg once daily (QD) via ELLIPTA + Placebo BID via DISKUS in treatment period 2. All participants entered a 2-week single blind wash-out period on FP 250 µg BID between the two treatment periods. The participants were followed up for approximately 7 days after completing Treatment Period 2. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|
|
Age, Continuous
|
27.8 Years
STANDARD_DEVIATION 10.35 • n=5 Participants
|
|
Sex: Female, Male
Female
|
43 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
31 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, Customized · African American/African Heritage
|
28 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, Customized · Asian - South East Asian Heritage
|
3 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, Customized · White - White/Caucasian/European Heritage
|
42 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Race, Customized · Mixed Race
|
1 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: At Week 2 of treatment period 1 and 2Population: ITT Population. Participants with non-missing covariates and data specific to endpoint were analyzed
The exercise challenge test is a stepped challenge on a treadmill. It was performed at 12 hrs post evening dose at the end of the 2-week treatment period, wherein the participants exercised sufficiently to reach a heart rate between 80 to 95 percent of their predicted maximum within 4 minutes (min) and maintained the heart rate with exercise for an additional 6 min followed immediately by serial assessments of FEV1 at 5, 10, 15, 30, 45 and 60 min post-exercise. Maximal percent decrease was calculated as pre-exercise FEV1 minus minimum post exercise FEV1 (smallest FEV1 value collected within one hr following exercise challenge) divided by pre-exercise FEV1 multiplied by 100. Pre-exercise FEV1 was defined as the FEV1 collected prior to the exercise challenge test at 12 hr post dose. ITT Population comprised of all participants randomized to treatment and who received at least one dose of study medication.
Outcome measures
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=70 Participants
Participants were administered FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=69 Participants
Participants were administered FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Maximal Percent Decrease in Forced Expiratory Volume in One Second (FEV1) Following Exercise Challenge at 12 Hours (Hrs) Post Evening Dose From Pre-exercise FEV1.
|
15.02 Percentage of FEV1
Standard Error 1.058
|
16.71 Percentage of FEV1
Standard Error 1.095
|
SECONDARY outcome
Timeframe: At Week 2 of treatment period 1 and 2Population: ITT Population. Participants with non-missing covariates and data specific to endpoint were analyzed
The exercise challenge test is a stepped challenge on a treadmill. It was performed at 23 hrs post evening dose at the end of the 2-week treatment period, wherein the participants exercised sufficiently to reach a heart rate between 80 to 95 percent of their predicted maximum within 4 min and maintained the heart rate with exercise for an additional 6 min followed immediately by serial assessments of FEV1 at 5, 10, 15, 30, 45 and 60 min post-exercise. Maximal percent decrease was calculated as pre-exercise FEV1 minus minimum post exercise FEV1 (smallest FEV1 value collected within one hr following exercise challenge) divided by pre-exercise FEV1 multiplied by 100. Pre-exercise FEV1 was defined as the FEV1 collected prior to the exercise challenge test at 23 hr post dose.
Outcome measures
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=68 Participants
Participants were administered FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=69 Participants
Participants were administered FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Maximal Percent Decrease in FEV1 Following Exercise Challenge at 23 Hrs Post Evening Dose From Pre-exercise FEV1.
|
11.90 Percentage of FEV1
Standard Error 1.020
|
14.05 Percentage of FEV1
Standard Error 1.051
|
SECONDARY outcome
Timeframe: At Week 2 of treatment period 1 and 2Population: ITT Population. Participants with non-missing covariates and data specific to endpoint were analyzed
The blinded treatment exercise challenge test was performed at the end of 2-weeks of treatment period 1 and treatment period 2 on a treadmill at 12 hrs and 23 hrs after administration of the evening dose of study treatment. The challenge was followed immediately by serial assessments of FEV1 at 5, 10, 15, 30, 45 and 60 min post-exercise. Pre-exercise FEV1 was defined as the FEV1 value collected prior to the exercise challenge test at 23 hrs post-dose. Number of participants listed is the number in the ITT population. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Outcome measures
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=73 Participants
Participants were administered FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=72 Participants
Participants were administered FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Proportion of Participants With a 30 Min Post-challenge FEV1 no More Than 5 Percent Lower Than Pre-exercise FEV1 Following the Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
FEV1 >=95% of pre-exercise FEV1, 12 hrs; n=70, 69
|
34 Participants
|
29 Participants
|
|
Proportion of Participants With a 30 Min Post-challenge FEV1 no More Than 5 Percent Lower Than Pre-exercise FEV1 Following the Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
FEV1 < 95% of pre-exercise FEV1, 12 hrs; n=70, 69
|
36 Participants
|
40 Participants
|
|
Proportion of Participants With a 30 Min Post-challenge FEV1 no More Than 5 Percent Lower Than Pre-exercise FEV1 Following the Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
FEV1 >=95% of pre-exercise FEV1, 23 hrs; n=68, 69
|
42 Participants
|
37 Participants
|
|
Proportion of Participants With a 30 Min Post-challenge FEV1 no More Than 5 Percent Lower Than Pre-exercise FEV1 Following the Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
FEV1 < 95% of pre-exercise FEV1, 23 hrs; n=68, 69
|
26 Participants
|
32 Participants
|
SECONDARY outcome
Timeframe: At Week 2 of treatment period 1 and 2Population: ITT Population. Participants with non-missing covariates and data specific to endpoint were analyzed
The exercise challenge testing at the end of 2 week treatment period was performed on a treadmill at 12 hrs and 23 hrs after administration of the evening dose of double-blind treatment. Following exercise challenge testing, post-exercise FEV1 values were assessed serially at 5, 10, 15, 30, 45 and 60 min. Pre-exercise FEV1 was defined as the FEV1 value collected prior to the exercise challenge test at 23 hrs post-dose. Number of participants listed is the number in the ITT population. Only those participants with data available at the specified time points were analyzed (represented by n=X, X in the category titles).
Outcome measures
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=73 Participants
Participants were administered FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=72 Participants
Participants were administered FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA in one of the two treatment periods. Each treatment period was of 2 weeks with a single blind 2 week wash-out period on FP 250 µg BID between the treatment periods. Albuterol/salbutamol was issued for rescue use during the run-in, wash-out and treatment periods as needed.
|
|---|---|---|
|
Weighted Mean 0-60 Min for Percentage Decrease From Pre-exercise FEV1 Following Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
12 hrs post-dose; n=67, 66
|
5.87 Percentage of FEV1
Standard Error 0.663
|
6.52 Percentage of FEV1
Standard Error 0.680
|
|
Weighted Mean 0-60 Min for Percentage Decrease From Pre-exercise FEV1 Following Exercise Challenge at 12 Hrs and 23 Hrs Post Evening Dose.
23 hrs post-dose; n=68, 67
|
3.98 Percentage of FEV1
Standard Error 0.699
|
5.73 Percentage of FEV1
Standard Error 0.747
|
Adverse Events
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
Serious adverse events
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=73 participants at risk
FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=72 participants at risk
FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA
|
|---|---|---|
|
Infections and infestations
Gastroenteritis
|
1.4%
1/73 • Number of events 1 • The on-treatment adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (approximately up to 51 days).
ITT Population
|
0.00%
0/72 • The on-treatment adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (approximately up to 51 days).
ITT Population
|
Other adverse events
| Measure |
FF/VI 100/25 µg QD Via ELLIPTA + Placebo BID Via DISKUS
n=73 participants at risk
FF/VI 100/25 µg QD via ELLIPTA + Placebo BID via DISKUS
|
FP 250 µg BID Via DISKUS + Placebo QD Via ELLIPTA
n=72 participants at risk
FP 250 µg BID via DISKUS + Placebo QD via ELLIPTA
|
|---|---|---|
|
Infections and infestations
Upper respiratory tract infection
|
6.8%
5/73 • Number of events 5 • The on-treatment adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (approximately up to 51 days).
ITT Population
|
5.6%
4/72 • Number of events 4 • The on-treatment adverse events (AEs) and serious adverse events (SAEs) were collected from the start of study treatment until the follow-up contact (approximately up to 51 days).
ITT Population
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER