Trial Outcomes & Findings for A Study to Evaluate the 24 Hour Spirometric Effect (FEV1) of Fluticasone Furoate/Vilanterol Inhalation Powder (100mcg Fluticasone Furoate (FF)/25mcg Vilanterol (VI)) Compared With Salmeterol/Fluticasone Propionate Inhalation Powder (50mcg Salmeterol/500mcg Fluticasone Propionate (FP)) (NCT NCT01342913)
NCT ID: NCT01342913
Last Updated: 2018-08-31
Results Overview
Pulmonary function was measured by forced expiratory volume in one second (FEV1). The weighted mean was calculated from the pre-dose FEV1 and 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 on Treatment Day 84. Baseline trough FEV1 was 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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
528 participants
Primary outcome timeframe
Baseline and Day 84
Results posted on
2018-08-31
Participant Flow
At Visit 1, participants entered a 2-week, single-blind (placebo) Run-in Period to obtain Baseline assessments of 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, double-blind 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.
|
Salmeterol/FP 50/500 µg BID
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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 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 Run-in Period
STARTED
|
702
|
0
|
0
|
|
2-week Run-in Period
COMPLETED
|
528
|
0
|
0
|
|
2-week Run-in Period
NOT COMPLETED
|
174
|
0
|
0
|
|
Double-Blind Treatment Period
STARTED
|
0
|
262
|
266
|
|
Double-Blind Treatment Period
COMPLETED
|
0
|
246
|
243
|
|
Double-Blind Treatment Period
NOT COMPLETED
|
0
|
16
|
23
|
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.
|
Salmeterol/FP 50/500 µg BID
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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 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 Run-in Period
Inclusion/Exclusion Criteria Not Met
|
66
|
0
|
0
|
|
2-week Run-in Period
Physician Decision
|
6
|
0
|
0
|
|
2-week Run-in Period
Withdrawal by Subject
|
7
|
0
|
0
|
|
2-week Run-in Period
Adverse Event
|
2
|
0
|
0
|
|
2-week Run-in Period
Protocol Violation
|
5
|
0
|
0
|
|
2-week Run-in Period
Continuation Criteria Not Met
|
88
|
0
|
0
|
|
Double-Blind Treatment Period
Adverse Event
|
0
|
3
|
6
|
|
Double-Blind Treatment Period
Lack of Efficacy
|
0
|
2
|
3
|
|
Double-Blind Treatment Period
Protocol Violation
|
0
|
6
|
9
|
|
Double-Blind Treatment Period
Lost to Follow-up
|
0
|
1
|
3
|
|
Double-Blind Treatment Period
Physician Decision
|
0
|
2
|
0
|
|
Double-Blind Treatment Period
Withdrawal by Subject
|
0
|
2
|
2
|
Baseline Characteristics
A Study to Evaluate the 24 Hour Spirometric Effect (FEV1) of Fluticasone Furoate/Vilanterol Inhalation Powder (100mcg Fluticasone Furoate (FF)/25mcg Vilanterol (VI)) Compared With Salmeterol/Fluticasone Propionate Inhalation Powder (50mcg Salmeterol/500mcg Fluticasone Propionate (FP))
Baseline characteristics by cohort
| Measure |
Salmeterol/FP 50/500 µg BID
n=262 Participants
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=266 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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=528 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
62.9 Years
STANDARD_DEVIATION 9.07 • n=99 Participants
|
63.0 Years
STANDARD_DEVIATION 8.10 • n=107 Participants
|
62.9 Years
STANDARD_DEVIATION 8.59 • n=206 Participants
|
|
Sex: Female, Male
Female
|
41 Participants
n=99 Participants
|
54 Participants
n=107 Participants
|
95 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
221 Participants
n=99 Participants
|
212 Participants
n=107 Participants
|
433 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
1 participants
n=99 Participants
|
0 participants
n=107 Participants
|
1 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian-South East Asian Heritage
|
53 participants
n=99 Participants
|
48 participants
n=107 Participants
|
101 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White-Arabic/North African Hertage
|
2 participants
n=99 Participants
|
1 participants
n=107 Participants
|
3 participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian/European Heritage
|
206 participants
n=99 Participants
|
217 participants
n=107 Participants
|
423 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 84Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least 1 dose of double-blind medication. Randomized participants were assumed to have received double-blind medication unless definitive evidence to the contrary existed. Only participants available at the indicated time point were assessed.
Pulmonary function was measured by forced expiratory volume in one second (FEV1). The weighted mean was calculated from the pre-dose FEV1 and 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 on Treatment Day 84. Baseline trough FEV1 was 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.
Outcome measures
| Measure |
Salmeterol/FP 50/500 µg BID
n=233 Participants
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=224 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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
|
0.108 Liters
Standard Error 0.0145
|
0.130 Liters
Standard Error 0.0148
|
SECONDARY outcome
Timeframe: Day 1Population: ITT Population. Only participants available at the indicated time point were assessed.
Time to onset on Treatment Day 1 is defined as the time to an increase of 100 milliliters (mL) from Baseline in FEV1. Time of 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 |
Salmeterol/FP 50/500 µg BID
n=260 Participants
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=260 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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
|
28 Minutes
Interval 5.0 to 240.0
|
16 Minutes
Interval 5.0 to 240.0
|
SECONDARY outcome
Timeframe: Baseline and Day 85Population: Only participants available at the indicated time point were assessed.
Pulmonary function was measured by forced expiratory volume in one second (FEV1). Trough FEV1 was defined as the 24-hour FEV1 assessment, which was obtained on Day 85. Baseline is defined as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Change from Baseline was calculated as the average of the Day 85 values minus the Baseline value.
Outcome measures
| Measure |
Salmeterol/FP 50/500 µg BID
n=245 Participants
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=242 Participants
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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 in Trough FEV1 on Treatment Day 85
|
0.088 Liters
Standard Error 0.0154
|
0.111 Liters
Standard Error 0.0155
|
Adverse Events
Salmeterol/FP 50/500 µg BID
Serious events: 3 serious events
Other events: 30 other events
Deaths: 0 deaths
FF/VI 100/25 µg QD
Serious events: 6 serious events
Other events: 32 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Salmeterol/FP 50/500 µg BID
n=262 participants at risk
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=266 participants at risk
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.76%
2/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Infections and infestations
Infective exacerbation of chronic obstructive airways diseas
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Infections and infestations
Sialoadenitis
|
0.38%
1/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.00%
0/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.75%
2/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Cardiac disorders
Coronary artery disease
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Gastrointestinal disorders
Food poisoning
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
0.38%
1/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
Other adverse events
| Measure |
Salmeterol/FP 50/500 µg BID
n=262 participants at risk
Participants received a Salmeterol and Fluticasone Propionate (FP) 50/500 microgram (µg) inhalation (available as a combination dry inhalation powder of Salmeterol 50 µg and FP 500 µg in 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=266 participants at risk
Participants received a Fluticasone Furoate /Vilanterol (FF/VI) 100/25 µg inhalation (available as 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
|
6.9%
18/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
7.5%
20/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Infections and infestations
Nasopharyngitis
|
4.6%
12/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
3.0%
8/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
1.1%
3/262 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
3.8%
10/266 • Serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until Follow-up (up to 12 weeks).
All AEs and SAEs were followed until resolution, until the condition stabilized, until the event was otherwise explained, or until the participant was lost to follow-up.
|
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