Trial Outcomes & Findings for A 24-week Study of Fluticasone Furoate/Vilanterol Inhalation Powder in Subjects of Asian Ancestry With COPD (NCT NCT01376245)

Last Updated: 2017-01-11

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. Trough FEV1 was defined as the pre-dose and pre-bronchodilator FEV1, which was obtained at each clinic visit. Baseline is defined as the mean of the two assessments made 30 minutes pre-dose and 5 minutes pre-dose on Treatment Day 1.Trough FEV1 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing at each clinic visit. Change from Baseline was calculated as the average at each clinic visit minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, smoking status at screening (stratum), baseline - mean of the two assessments made 30 minutes pre-dose and immediately pre-dose on Day 1, day, day by baseline and day by treatment interactions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

646 participants

Primary outcome timeframe

Baseline to Day 169

Results posted on

2017-01-11

Participant Flow

Eligible participants (par.) completed a 2-week Run-in Period for symptom scores at baseline and to establish a stable baseline. Par. were then randomized to a 24-week (wk) Treatment Period. 880 par. were screened, 744 entered the RIP and 646 par were randomized, out of which 643 par received \>=1 study treatment dose.

Participant milestones

Participant milestones
Measure	Placebo- Run-in Participants received placebo once daily (OD) in the morning for 2 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	Placebo Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF /VI 50/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.
2-wk Single-blind Placebo Run-in Period STARTED	744	0	0	0	0
2-wk Single-blind Placebo Run-in Period COMPLETED	643	0	0	0	0
2-wk Single-blind Placebo Run-in Period NOT COMPLETED	101	0	0	0	0
24-week, Double-blind Treatment Period STARTED	0	162	160	161	160
24-week, Double-blind Treatment Period COMPLETED	0	130	135	138	134
24-week, Double-blind Treatment Period NOT COMPLETED	0	32	25	23	26

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo- Run-in Participants received placebo once daily (OD) in the morning for 2 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	Placebo Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF /VI 50/25 µg OD Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.
2-wk Single-blind Placebo Run-in Period Did Not Meet Continuation Criteria	66	0	0	0	0
2-wk Single-blind Placebo Run-in Period Adverse Event	4	0	0	0	0
2-wk Single-blind Placebo Run-in Period Lost to Follow-up	1	0	0	0	0
2-wk Single-blind Placebo Run-in Period Physician Decision	2	0	0	0	0
2-wk Single-blind Placebo Run-in Period Withdrawal by Subject	28	0	0	0	0
24-week, Double-blind Treatment Period Adverse Event	0	16	7	8	18
24-week, Double-blind Treatment Period Lack of Efficacy	0	4	5	4	3
24-week, Double-blind Treatment Period Protocol Violation	0	2	0	2	1
24-week, Double-blind Treatment Period Met Protocol-Defined Stopping Criteria	0	2	3	1	0
24-week, Double-blind Treatment Period Lost to Follow-up	0	2	0	1	1
24-week, Double-blind Treatment Period Physician Decision	0	0	1	1	0
24-week, Double-blind Treatment Period Withdrawal by Subject	0	6	9	6	3

Baseline Characteristics

A 24-week Study of Fluticasone Furoate/Vilanterol Inhalation Powder in Subjects of Asian Ancestry With COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=162 Participants Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF /VI 50/25 µg OD n=160 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD n=161 Participants Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD n=160 Participants Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	Total n=643 Participants Total of all reporting groups
Age, Continuous	64.7 Years STANDARD_DEVIATION 8.78 • n=5 Participants	65.2 Years STANDARD_DEVIATION 8.41 • n=7 Participants	65.1 Years STANDARD_DEVIATION 9.19 • n=5 Participants	62.7 Years STANDARD_DEVIATION 8.65 • n=4 Participants	64.4 Years STANDARD_DEVIATION 8.80 • n=21 Participants
Gender Female	16 Participants n=5 Participants	16 Participants n=7 Participants	12 Participants n=5 Participants	15 Participants n=4 Participants	59 Participants n=21 Participants
Gender Male	146 Participants n=5 Participants	144 Participants n=7 Participants	149 Participants n=5 Participants	145 Participants n=4 Participants	584 Participants n=21 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	151 Participants n=5 Participants	149 Participants n=7 Participants	150 Participants n=5 Participants	148 Participants n=4 Participants	598 Participants n=21 Participants
Race/Ethnicity, Customized Asian - South East Asian	11 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	12 Participants n=4 Participants	45 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline to Day 169

Population: Intent-to-Treat (ITT) Population: all randomized par. who received at least one dose of study medication. Number of par. presented represents those with data available at the time point being presented, however, all par. in the ITT population without missing covariate information with at least one post BL measurement are included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=126 Participants Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF/VI 50/25 µg OD n=134 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD n=136 Participants Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD n=131 Participants Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.
Mean Change From Baseline in Clinic Visit Pre-dose Trough FEV1 at Day 169	-0.027 Liters Standard Error 0.0184	0.113 Liters Standard Error 0.0183	0.152 Liters Standard Error 0.0181	0.167 Liters Standard Error 0.0182

SECONDARY outcome

Timeframe: Baseline (BL) and Day 168

Population: ITT Population. Only those participants available at the indicated time point were assessed.

CRQ-SAS measures 4 domains (fatigue, emotional function, mastery and dyspnea) of functioning of participants (par.) with COPD: mastery (amount of control the par. feels he/she has over COPD symptoms); fatigue (how tired the par. feels); emotional function (how anxious/depressed the par. feels); and dyspnea (how short of breath the par. feels during physical activities). Each domain is calculated separately and measured on a scale of 1-7 (1=maximum impairment; 7=no impairment). Dyspnea domain score is the mean of all non-missing responses for that domain. Only the dyspnea domain was measured as a secondary outcome. BL scores are the derived scores for each domain and total at Day 1 pre-dose. Change from BL was calculated as the average of the Day 168 values minus the BL value. Analysis performed used a repeated measures model with covariates of treatment, smoking status at screening (stratum), BL (derived scores at Day 1 pre-dose), day, day by BL, and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=128 Participants Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF/VI 50/25 µg OD n=134 Participants Participants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD n=136 Participants Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD n=132 Participants Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.
Mean Change From Baseline in Chronic Respiratory Disease Questionnaire Self-administered Standardized (CRQ-SAS) Dyspnea Domain Score at Day 168	0.09 Scores on a scale Standard Error 0.081	0.30 Scores on a scale Standard Error 0.080	0.43 Scores on a scale Standard Error 0.079	0.37 Scores on a scale Standard Error 0.080

Adverse Events

Placebo

Serious events: 14 serious events

Other events: 27 other events

Deaths: 0 deaths

FF/VI 50/25 µg OD

Serious events: 9 serious events

Other events: 33 other events

Deaths: 0 deaths

FF/VI 100/25 µg OD

Serious events: 7 serious events

Other events: 34 other events

Deaths: 0 deaths

FF/VI 200/25 µg OD

Serious events: 14 serious events

Other events: 40 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=162 participants at risk Participants received placebo once daily (OD) in the morning for 24 weeks. In addition, participants were provided supplemental albuterol/salbutamol (metered dose inhaler \[MDI\] or nebules) to be used as needed throughout the study.	FF/VI 50/25 µg OD n=160 participants at risk articipants received Fluticasone Furoate (FF)/Vilanterol (VI) 50/25 micrograms (µg) OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 100/25 µg OD n=161 participants at risk Participants received FF/VI 100/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.	FF/VI 200/25 µg OD n=160 participants at risk Participants received FF/VI 200/25 µg OD in the morning over the 24-week treatment period. In addition, participants were provided albuterol/salbutamol (MDI or nebules) to be used as needed throughout the study.
Infections and infestations Upper respiratory tract infection	9.3% 15/162 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	10.0% 16/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	11.8% 19/161 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	8.8% 14/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Infections and infestations Nasopharyngitis	4.3% 7/162 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	8.1% 13/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	5.6% 9/161 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	11.9% 19/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
General disorders Pyrexia	3.1% 5/162 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	1.9% 3/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	2.5% 4/161 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	1.9% 3/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Respiratory, thoracic and mediastinal disorders Cough	1.2% 2/162 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	1.2% 2/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	3.7% 6/161 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	1.9% 3/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.
Vascular disorders Hypertension	0.62% 1/162 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	0.62% 1/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	1.2% 2/161 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.	3.1% 5/160 • Serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of the study medication to the end of treatment (up to Week 24). An on-treatment AE or SAE is defined as an AE with an onset on or after the start date of study medication, but not later than one day after the last date of study medication. SAEs and AEs were collected in members of the ITT Population, comprised of all participants randomized to treatment, who received at least one dose of the study medication.

Additional Information

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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.
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