Trial Outcomes & Findings for A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol With Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01879410)
NCT ID: NCT01879410
Last Updated: 2017-11-08
Results Overview
FEV1 is a measure of lung function and is 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 post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 hours (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Analysis was performed using an analysis of covariance model with covariates of baseline FEV1 (mean of the two assessments made 30 mins and 5 mins pre-dose on Day 1), smoking status, and treatment. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
700 participants
Primary outcome timeframe
Baseline and Day 84
Results posted on
2017-11-08
Participant Flow
A total of 700 participants representing the enrolled participants, were randomized to study treatment. Of these, 697 comprised the Intent-to-Treat Population (participants randomized to treatment who received \>=1 dose of randomized study medication in the treatment period).
Participant milestones
| Measure |
UMEC/VI 62.5/25 µg
Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg)) once daily (QD) in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 µg
Participants received fluticasone propionate/salmeterol (FSC) 250/50 µg twice daily (BID) in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
350
|
350
|
|
Overall Study
Intent-to-Treat Population
|
349
|
348
|
|
Overall Study
COMPLETED
|
326
|
312
|
|
Overall Study
NOT COMPLETED
|
24
|
38
|
Reasons for withdrawal
| Measure |
UMEC/VI 62.5/25 µg
Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg)) once daily (QD) in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 µg
Participants received fluticasone propionate/salmeterol (FSC) 250/50 µg twice daily (BID) in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
9
|
14
|
|
Overall Study
Lack of Efficacy
|
4
|
6
|
|
Overall Study
Protocol Violation
|
1
|
7
|
|
Overall Study
Lost to Follow-up
|
2
|
1
|
|
Overall Study
Withdrawal by Subject
|
7
|
8
|
|
Overall Study
Randomised in Error
|
1
|
2
|
Baseline Characteristics
A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol With Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
UMEC/VI 62.5/25 mcg
n=349 Participants
Participants received UMEC/VI 62.5/25 µg QD in the morning via a DPI and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 mcg
n=348 Participants
Participants received FSC 250/50 µg BID in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
Total
n=697 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.2 Years
STANDARD_DEVIATION 8.57 • n=93 Participants
|
64.0 Years
STANDARD_DEVIATION 8.53 • n=4 Participants
|
63.6 Years
STANDARD_DEVIATION 8.55 • n=27 Participants
|
|
Sex: Female, Male
Female
|
85 Participants
n=93 Participants
|
84 Participants
n=4 Participants
|
169 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
264 Participants
n=93 Participants
|
264 Participants
n=4 Participants
|
528 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
18 Particpants
n=93 Participants
|
13 Particpants
n=4 Participants
|
31 Particpants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
7 Particpants
n=93 Participants
|
2 Particpants
n=4 Participants
|
9 Particpants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian
|
4 Particpants
n=93 Participants
|
2 Particpants
n=4 Participants
|
6 Particpants
n=27 Participants
|
|
Race/Ethnicity, Customized
White
|
317 Particpants
n=93 Participants
|
326 Particpants
n=4 Participants
|
643 Particpants
n=27 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native & White
|
3 Particpants
n=93 Participants
|
5 Particpants
n=4 Participants
|
8 Particpants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline and Day 84Population: Intent-to-Treat (ITT) Population: all randomized participants who received at least 1 dose of randomized study drug in the Treatment Period. Participants analyzed were those with data available at the presented time point; but, all participants without missing covariate information and with \>= post BL measurement were included in the analysis.
FEV1 is a measure of lung function and is 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 post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 hours (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Analysis was performed using an analysis of covariance model with covariates of baseline FEV1 (mean of the two assessments made 30 mins and 5 mins pre-dose on Day 1), smoking status, and treatment. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=349 Participants
Participants received UMEC/VI 62.5/25 µg QD in the morning via a DPI and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 mcg
n=348 Participants
Participants received FSC 250/50 µg BID in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Change From Baseline (BL) in 0 to 24 Hour Weighted Mean Forced Expiratory Volume Over 1 Second (FEV1) at Day 84
|
0.213 Liters
Standard Error 0.0137
|
0.112 Liters
Standard Error 0.0139
|
SECONDARY outcome
Timeframe: Baseline and Day 85Population: ITT Population. Participants analyzed were those with data available at the presented time point; but, all participants without missing covariate information were included in the analysis.
FEV1 is a measure of lung function and is defined as the maximal amount of air that can be forcefully exhaled in one second. Baseline is defined as the mean of the assessments made 30 and 5 minutes (min) pre-dose on treatment Day 1. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing on Day 84. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the 2 assessments made 30 min and 5 min pre-dose on Day 1), smoking status, day, day by baseline and day by treatment interactions. The model used all available trough FEV1 values recorded on Days 28, 56, 84, and 85. Missing data were not directly imputed in this analysis; however, all non-missing data for a participant were used within the analysis to estimate the treatment effect for trough FEV1 at Day 85. Change from baseline was calculated as the value at Day 84 minus the value at Baseline.
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=349 Participants
Participants received UMEC/VI 62.5/25 µg QD in the morning via a DPI and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 mcg
n=348 Participants
Participants received FSC 250/50 µg BID in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Change From Baseline(BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85
|
0.185 Liters
Standard Error 0.0138
|
0.087 Liters
Standard Error 0.0140
|
Adverse Events
UMEC/VI 62.5/25 mcg
Serious events: 11 serious events
Other events: 36 other events
Deaths: 0 deaths
FSC 250/50 mcg
Serious events: 13 serious events
Other events: 28 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
UMEC/VI 62.5/25 mcg
n=349 participants at risk
Participants received UMEC/VI 62.5/25 µg QD in the morning via a DPI and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 mcg
n=348 participants at risk
Participants received FSC 250/50 µg BID in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Infections and infestations
Pneumonia
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
1.1%
4/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Infections and infestations
Appendicitis
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Infections and infestations
Lobar pneumonia
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
1.1%
4/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
1.1%
4/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Pleurisy
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax spontaneous
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Infections and infestations
Perirectal abscess
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Infections and infestations
Respiratory tract infection viral
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Cardiac disorders
Myocardial infarction
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Cardiac disorders
Cardiac failure
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung adenocarcinoma
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer
|
0.00%
0/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.29%
1/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Psychiatric disorders
Alcohol abuse
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Vascular disorders
Peripheral artery thrombosis
|
0.29%
1/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
0.00%
0/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
Other adverse events
| Measure |
UMEC/VI 62.5/25 mcg
n=349 participants at risk
Participants received UMEC/VI 62.5/25 µg QD in the morning via a DPI and placebo in the morning and evening via a separate DPI for 12 weeks.
|
FSC 250/50 mcg
n=348 participants at risk
Participants received FSC 250/50 µg BID in the morning and evening via a DPI and placebo in the morning via a separate DPI for 12 weeks.
|
|---|---|---|
|
Nervous system disorders
Headache
|
6.9%
24/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
6.6%
23/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
|
Infections and infestations
Nasopharyngitis
|
4.0%
14/349 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in the treatment period
|
1.7%
6/348 • Serious adverse events (SAEs) and non-serious adverse events (AEs) collected from the start of study treatment up to the Follow-up Visit or premature withdrawal (up to Day 94)
SAEs and non-serious AEs are reported for members of the ITT Population,comprised of all randomized participants who received at least 1 dose of randomized study drug in 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