Trial Outcomes & Findings for Study to Evaluate 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 (NCT NCT01323634)

Last Updated: 2017-11-08

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 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 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

519 participants

Primary outcome timeframe

Baseline (Day 1) and Day 84

Results posted on

2017-11-08

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

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 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	733	0	0
2-week Run-in Period COMPLETED	521	0	0
2-week Run-in Period NOT COMPLETED	212	0	0
Double-Blind (DB) Treatment Period STARTED	0	260	261
Double-Blind (DB) Treatment Period COMPLETED	0	235	239
Double-Blind (DB) Treatment Period NOT COMPLETED	0	25	22

Reasons for withdrawal

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 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	125	0	0
2-week Run-in Period Continuation Criteria not Met	73	0	0
2-week Run-in Period Withdrawal by Subject	7	0	0
2-week Run-in Period Physician Decision	5	0	0
2-week Run-in Period Protocol Violation	1	0	0
2-week Run-in Period Adverse Event	1	0	0
Double-Blind (DB) Treatment Period Adverse Event	0	8	4
Double-Blind (DB) Treatment Period Lack of Efficacy	0	0	2
Double-Blind (DB) Treatment Period Protocol Violation	0	6	7
Double-Blind (DB) Treatment Period Lost to Follow-up	0	1	1
Double-Blind (DB) Treatment Period Physician Decision	0	2	3
Double-Blind (DB) Treatment Period Withdrawal by Subject	0	7	4
Double-Blind (DB) Treatment Period Did not Receive DB Study Medication	0	1	1

Baseline Characteristics

Study to Evaluate 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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	FSC 250/50 µg BID n=259 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 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.	Total n=519 Participants Total of all reporting groups
Sex: Female, Male Male	169 Participants n=93 Participants	164 Participants n=4 Participants	333 Participants n=27 Participants
Sex: Female, Male Female	90 Participants n=93 Participants	96 Participants n=4 Participants	186 Participants n=27 Participants
Age, Continuous	61.2 Years STANDARD_DEVIATION 8.32 • n=93 Participants	61.1 Years STANDARD_DEVIATION 7.92 • n=4 Participants	61.2 Years STANDARD_DEVIATION 8.11 • n=27 Participants
Race/Ethnicity, Customized African American/ African Heritage	9 participants n=93 Participants	5 participants n=4 Participants	14 participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 participants n=93 Participants	1 participants n=4 Participants	1 participants n=27 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	250 participants n=93 Participants	254 participants n=4 Participants	504 participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1) and Day 84

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of study drug. Only participants available at the indicated time point were assessed.

Outcome measures

Outcome measures
Measure	FSC 250/50 µg BID n=213 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 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=228 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	0.094 Liters Standard Error 0.0158	0.174 Liters Standard Error 0.0153

SECONDARY outcome

Timeframe: Day 1

Population: 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, 30 min, 60 min, 120 min, and 240 min) post-dose.

Outcome measures

Outcome measures
Measure	FSC 250/50 µg BID n=257 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 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 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	15 Minutes Interval 5.0 to 240.0

Adverse Events

FSC 250/50 µg BID

Serious events: 8 serious events

Other events: 18 other events

Deaths: 0 deaths

FF/VI 100/25 µg QD

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	FSC 250/50 µg BID n=259 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 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 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.
Respiratory, thoracic and mediastinal disorders Chronic onstructive pulmonary disease	1.2% 3/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Cardiac disorders Atrial fibrillation	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Cardiac disorders Cardiac failure congestive	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Cardiac disorders Cardio-respiratory arrest	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Hepatobiliary disorders Cholecystitis	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Infections and infestations Bronchitis	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Injury, poisoning and procedural complications Rib fracture	0.39% 1/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.00% 0/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Musculoskeletal and connective tissue disorders Lumbar spinal stenosis	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Musculoskeletal and connective tissue disorders Synovial cyst	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Vascular disorders Deep vein thrombosis	0.00% 0/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	0.38% 1/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.

Other adverse events

Other adverse events
Measure	FSC 250/50 µg BID n=259 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 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 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	4.2% 11/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	6.2% 16/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.
Infections and infestations Nasopharyngitis	2.7% 7/259 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.	3.1% 8/260 • Serious adverse events (SAEs) and non-serious adverse events were collected from Baseline to the end of the study (up to 12 weeks). SAEs and non-serious adverse events are reported for members of the Intent-to-Treat Population, comprised of all randomized participants who received at least one dose of study medication during the treatment period.

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