Trial Outcomes & Findings for Study Evaluating the 24-Hour Pulmonary Function Profile of Fluticasone Furoate (FF) /GW642444 (Vilanterol) (VI) Inhalation Powder 100/25mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01323621)
NCT ID: NCT01323621
Last Updated: 2018-02-15
Results Overview
Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
512 participants
Primary outcome timeframe
Baseline (Day 1) and Day 84
Results posted on
2018-02-15
Participant Flow
At Visit 1, eligible participants entered a 2-week, single blind (placebo) Run-In Period to obtain Baseline assessments of albuterol (salbutamol) use and to evaluate adherence with study treatment and procedures, diary card completion, and assessment of disease stability. At Visit 2, participants were randomized to a 12-week Treatment Period.
Participant milestones
| Measure |
Placebo + Salbutamol
Participants were instructed to take single-blind placebo (ACCUHALER/DISKUS and Novel Dry Powder Inhaler \[NDPI\]): one inhalation each morning from each device, and one inhalation from the ACCUHALER/DISKUS in the evening. In addition, all participants received supplemental albuterol (salbutamol) (metered dose inhaler \[MDI\] and/or nebules) to be used on an as-needed basis. Ipratropium bromide alone was permitted, provided that the participant was on a stable dose from Visit 1 (Screening) and remained on the stable dose throughout the study; however, Ipratropium must have been withheld for 4 hours prior to and during each clinic visit.
|
FSC 250/50 µg BID
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|---|
|
2-week, Single-blind Run In Period
STARTED
|
739
|
0
|
0
|
|
2-week, Single-blind Run In Period
COMPLETED
|
511
|
0
|
0
|
|
2-week, Single-blind Run In Period
NOT COMPLETED
|
228
|
0
|
0
|
|
12-week, Double-blind Treatment Period
STARTED
|
0
|
252
|
259
|
|
12-week, Double-blind Treatment Period
COMPLETED
|
0
|
237
|
239
|
|
12-week, Double-blind Treatment Period
NOT COMPLETED
|
0
|
15
|
20
|
Reasons for withdrawal
| Measure |
Placebo + Salbutamol
Participants were instructed to take single-blind placebo (ACCUHALER/DISKUS and Novel Dry Powder Inhaler \[NDPI\]): one inhalation each morning from each device, and one inhalation from the ACCUHALER/DISKUS in the evening. In addition, all participants received supplemental albuterol (salbutamol) (metered dose inhaler \[MDI\] and/or nebules) to be used on an as-needed basis. Ipratropium bromide alone was permitted, provided that the participant was on a stable dose from Visit 1 (Screening) and remained on the stable dose throughout the study; however, Ipratropium must have been withheld for 4 hours prior to and during each clinic visit.
|
FSC 250/50 µg BID
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|---|
|
2-week, Single-blind Run In Period
Not Met Inclusion/Exclusion Criteria
|
121
|
0
|
0
|
|
2-week, Single-blind Run In Period
Physician Decision
|
7
|
0
|
0
|
|
2-week, Single-blind Run In Period
Withdrawal by Subject
|
12
|
0
|
0
|
|
2-week, Single-blind Run In Period
Protocol Violation
|
1
|
0
|
0
|
|
2-week, Single-blind Run In Period
Lost to Follow-up
|
1
|
0
|
0
|
|
2-week, Single-blind Run In Period
Did Not Meet Continuation Criteria
|
86
|
0
|
0
|
|
12-week, Double-blind Treatment Period
Adverse Event
|
0
|
1
|
5
|
|
12-week, Double-blind Treatment Period
Lack of Efficacy
|
0
|
2
|
6
|
|
12-week, Double-blind Treatment Period
Protocol Violation
|
0
|
4
|
4
|
|
12-week, Double-blind Treatment Period
Lost to Follow-up
|
0
|
1
|
0
|
|
12-week, Double-blind Treatment Period
Physician Decision
|
0
|
2
|
1
|
|
12-week, Double-blind Treatment Period
Withdrawal by Subject
|
0
|
5
|
4
|
Baseline Characteristics
Study Evaluating the 24-Hour Pulmonary Function Profile of Fluticasone Furoate (FF) /GW642444 (Vilanterol) (VI) Inhalation Powder 100/25mcg Once Daily Compared With Fluticasone Propionate/Salmeterol Inhalation Powder 250/50mcg Twice Daily in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
FSC 250/50 µg BID
n=252 Participants
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
n=259 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
Total
n=511 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61.7 Years
STANDARD_DEVIATION 9.05 • n=93 Participants
|
61.6 Years
STANDARD_DEVIATION 9.59 • n=4 Participants
|
61.6 Years
STANDARD_DEVIATION 9.32 • n=27 Participants
|
|
Sex: Female, Male
Female
|
85 Participants
n=93 Participants
|
78 Participants
n=4 Participants
|
163 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
167 Participants
n=93 Participants
|
181 Participants
n=4 Participants
|
348 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European Heritage
|
238 participants
n=93 Participants
|
241 participants
n=4 Participants
|
479 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
14 participants
n=93 Participants
|
17 participants
n=4 Participants
|
31 participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - Arabic/North African Heritage
|
0 participants
n=93 Participants
|
1 participants
n=4 Participants
|
1 participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline (Day 1) and Day 84Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study drug. Only those participants available at the indicated time points were assessed.
Pulmonary function was measured by forced expiratory volume in one second (FEV1), defined as the maximal amount of air that can be forcefully exhaled in one second. The weighted mean was calculated from the pre-dose FEV1 and the post-dose FEV1 measurements at 5, 15, 30, and 60 minutes (min) and 2, 4, 6, 8, 12, 13, 14, 16, 20, and 24 hours post-dose on Treatment Day 84. Baseline trough FEV1 was calculated as the mean of the two assessments made 30 and 5 minutes pre-dose on Treatment Day 1. Change from Baseline was calculated as the average of the Day 84 values minus the Baseline value. Analysis of covariance (ANCOVA) was conducted with covariates for country, smoking status, reversibility, and Baseline FEV1.
Outcome measures
| Measure |
FSC 250/50 µg BID
n=217 Participants
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
n=219 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|
|
Change From Baseline Trough in 24-Hour Weighted Mean FEV1 on Treatment Day 84
|
0.114 Liters
Standard Error 0.0183
|
0.142 Liters
Standard Error 0.0182
|
SECONDARY outcome
Timeframe: Baseline and Day 1Population: ITT Population
Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time to onset was calculated over 0 to 4 hours (5 min, 15 min, 30 min, 60 min, 120 min, and 240 min) post-dose.
Outcome measures
| Measure |
FSC 250/50 µg BID
n=251 Participants
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
n=258 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|
|
Time to Onset on Treatment Day 1
|
30 Minutes
Interval 5.0 to 240.0
|
16 Minutes
Interval 5.0 to 240.0
|
Adverse Events
FSC 250/50 µg BID
Serious events: 3 serious events
Other events: 10 other events
Deaths: 0 deaths
FF/VI 100/25 µg QD
Serious events: 5 serious events
Other events: 12 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
FSC 250/50 µg BID
n=252 participants at risk
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
n=259 participants at risk
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
|
0.00%
0/252
|
0.39%
1/259
|
|
Respiratory, thoracic and mediastinal disorders
Bronchitis chronic
|
0.00%
0/252
|
0.39%
1/259
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/252
|
0.39%
1/259
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.40%
1/252
|
0.00%
0/259
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/252
|
0.39%
1/259
|
|
Injury, poisoning and procedural complications
Comminuted fracture
|
0.40%
1/252
|
0.00%
0/259
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.40%
1/252
|
0.00%
0/259
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/252
|
0.39%
1/259
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/252
|
0.39%
1/259
|
|
Infections and infestations
Infective tenosynovitis
|
0.00%
0/252
|
0.39%
1/259
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma metastatic
|
0.00%
0/252
|
0.39%
1/259
|
Other adverse events
| Measure |
FSC 250/50 µg BID
n=252 participants at risk
Participants received a Fluticasone Propionate and Salmeterol (FSC) 250/50 microgram (µg) inhalation (available as a combination dry inhalation powder of Fluticasone 250 µg and Salmeterol 50 µg in a single strip) twice daily (BID) (morning and evening) from the ACCUHALER/DISKUS and placebo once daily (QD) in the morning from the NDPI over the course of 12 weeks.
|
FF/VI 100/25 µg QD
n=259 participants at risk
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as a dry inhalation powder in two separate strips of FF 100 µg and VI 25 µg) QD in the morning from the NDPI and placebo BID (morning and evening) from the ACCUHALER/DISKUS over the course of 12 weeks.
|
|---|---|---|
|
Nervous system disorders
Headache
|
4.0%
10/252
|
4.6%
12/259
|
Additional Information
GSK Response Center
GlaxoSmithKline
Phone: 866-435-7343
Results disclosure agreements
- Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
- Publication restrictions are in place
Restriction type: OTHER