Trial Outcomes & Findings for A Study to Evaluate the Efficacy and Safety of Umeclidinium Bromide/Vilanterol Compared With Fluticasone Propionate/Salmeterol Over 12 Weeks in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01822899)

Last Updated: 2017-09-06

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 (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), and smoking status.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

717 participants

Primary outcome timeframe

Baseline and Day 84

Results posted on

2017-09-06

Participant Flow

Participants who met the eligibility criteria at Screening (Visit 1) completed a 7- to 14-day Run-in Period, followed by a 12-week Treatment Period.

A total of 717 participants, representing the enrolled participants, were randomized to study treatment. Of these, 716 participants comprised the Intent-to-Treat Population (participants randomized to treatment who received \>=1 dose of randomized study medication in the treatment period).

Participant milestones

Participant milestones
Measure	UMEC/VI 62.5/25 µg Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Overall Study STARTED	358	358
Overall Study COMPLETED	334	340
Overall Study NOT COMPLETED	24	18

Reasons for withdrawal

Reasons for withdrawal
Measure	UMEC/VI 62.5/25 µg Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Overall Study Adverse Event	6	5
Overall Study Lack of Efficacy	6	3
Overall Study Protocol Violation	6	3
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	5	7

Baseline Characteristics

A Study to Evaluate the Efficacy and Safety of Umeclidinium Bromide/Vilanterol Compared With Fluticasone Propionate/Salmeterol Over 12 Weeks in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	UMEC/VI 62.5/25 µg n=358 Participants Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg n=358 Participants Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.	Total n=716 Participants Total of all reporting groups
Age, Continuous	61.8 Years STANDARD_DEVIATION 7.94 • n=5 Participants	61.4 Years STANDARD_DEVIATION 8.06 • n=7 Participants	61.6 Years STANDARD_DEVIATION 8.00 • n=5 Participants
Sex: Female, Male Female	97 Participants n=5 Participants	104 Participants n=7 Participants	201 Participants n=5 Participants
Sex: Female, Male Male	261 Participants n=5 Participants	254 Participants n=7 Participants	515 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	358 Participants n=5 Participants	358 Participants n=7 Participants	716 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 84

Population: Intent-to-Treat (ITT) Population: all participants (par.) randomized to treatment who received at least one dose of randomized study drug in the Treatment Period. Par. analyzed were those with data available at the presented time point but all par. without missing covariate information and with \>= post BL measurement were included in the analysis.

Outcome measures

Outcome measures
Measure	UMEC/VI 62.5/25 µg n=332 Participants Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg n=337 Participants Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Change From Baseline (BL) in 0 to 24 Hour Weighted Mean Serial Forced Expiratory Volume in One Second (FEV1) at Day 84	0.166 Liters Standard Error 0.0122	0.087 Liters Standard Error 0.0121

SECONDARY outcome

Timeframe: Baseline and Day 85

Population: 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. BL 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 FEV1values obtained 23 and 24 hours after the previous morning's dosing (i.e., trough FEV1 on Day 85 is 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, BL (mean of the two assessments made 30 min and 5 min pre-dose on Day 1), smoking status, day, and day by BL 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.

Outcome measures

Outcome measures
Measure	UMEC/VI 62.5/25 µg n=333 Participants Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg n=338 Participants Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) at Day 85	0.151 Liters Standard Error 0.0126	0.062 Liters Standard Error 0.0125

Adverse Events

UMEC/VI 62.5/25 µg

Serious events: 7 serious events

Other events: 39 other events

Deaths: 0 deaths

FSC 500/50 µg

Serious events: 2 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	UMEC/VI 62.5/25 µg n=358 participants at risk Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg n=358 participants at risk Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.84% 3/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Infections and infestations Herpes zoster	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Infections and infestations Sepsis	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Cardiac disorders Angina pectoris	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Gastrointestinal disorders Inguinal hernia	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
General disorders Sudden cardiac death	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Renal and urinary disorders Renal failure acute	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Skin and subcutaneous tissue disorders Skin burning sensation	0.28% 1/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	0.00% 0/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.

Other adverse events

Other adverse events
Measure	UMEC/VI 62.5/25 µg n=358 participants at risk Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks.	FSC 500/50 µg n=358 participants at risk Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks.
Nervous system disorders Headache	9.2% 33/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	7.0% 25/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.
Infections and infestations Nasopharyngitis	2.8% 10/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug in the Treatment Period.	3.1% 11/358 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the follow-up contact (up to 13 weeks). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one 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.
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