Trial Outcomes & Findings for A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol and Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT01817764)

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. Weighted mean is 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. Change from Baseline was calculated as the value at Day 84 minus the value at Baseline. Analysis was performed using an analysis of covariance of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), and smoking status. par.=participants.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

707 participants

Primary outcome timeframe

Baseline and Day 84

Results posted on

2017-11-08

Participant Flow

A total of 707 participants, representing the enrolled participants, were randomized to study treatment. Of these, 706 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 QD Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Overall Study STARTED	353	353
Overall Study COMPLETED	319	315
Overall Study NOT COMPLETED	34	38

Reasons for withdrawal

Reasons for withdrawal
Measure	UMEC/VI 62.5/25 µg QD Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Overall Study Adverse Event	7	10
Overall Study Lack of Efficacy	9	7
Overall Study Protocol Violation	7	5
Overall Study Lost to Follow-up	1	4
Overall Study Withdrawal by Subject	10	12

Baseline Characteristics

A Study to Compare the Efficacy and Safety of Umeclidinium/Vilanterol and Fluticasone Propionate/Salmeterol in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	UMEC/VI 62.5/25 µg QD n=353 Participants Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID n=353 Participants Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.	Total n=706 Participants Total of all reporting groups
Age, Continuous	62.5 Years STANDARD_DEVIATION 9.05 • n=5 Participants	63.0 Years STANDARD_DEVIATION 8.91 • n=7 Participants	62.8 Years STANDARD_DEVIATION 8.97 • n=5 Participants
Sex: Female, Male Female	100 Participants n=5 Participants	109 Participants n=7 Participants	209 Participants n=5 Participants
Sex: Female, Male Male	253 Participants n=5 Participants	244 Participants n=7 Participants	497 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	4 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White - White/Caucasian/European	341 Participants n=5 Participants	342 Participants n=7 Participants	683 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 84

Population: Intent-to-Treat (ITT) Population: all par. randomized to treatment who received \>=1 dose of randomized study medication in the treatment period. Only par. with analyzable data at the indicated time point were assessed, but all par. without missing covariate information and with \>=1 post-Baseline measurement were included in the analysis.

Outcome measures

Outcome measures
Measure	UMEC/VI 62.5/25 µg QD n=315 Participants Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID n=310 Participants Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Change From Baseline in 24-hour Weighted-mean Serial FEV1 on Treatment Day 84	0.165 Liters Standard Error 0.0130	0.091 Liters Standard Error 0.0131

SECONDARY outcome

Timeframe: Baseline and Day 85

Population: ITT Population. Only those participants with analyzable data at the indicated time point were assessed.

Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing/11 and 12 hours after evening dosing on Day 84. Change from Baseline is calculated as the Day 85 value minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), smoking status, day, and day by Baseline and day by treatment interactions.

Outcome measures

Outcome measures
Measure	UMEC/VI 62.5/25 µg QD n=317 Participants Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID n=312 Participants Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Change From Baseline in Trough FEV1 on Day 85	0.154 Liters Standard Error 0.0133	0.072 Liters Standard Error 0.0134

Adverse Events

UMEC/VI 62.5/25 µg QD

Serious events: 6 serious events

Other events: 38 other events

Deaths: 0 deaths

FSC 250/50 µg BID

Serious events: 10 serious events

Other events: 25 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	UMEC/VI 62.5/25 µg QD n=353 participants at risk Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID n=353 participants at risk Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Nervous system disorders Headache	6.5% 23/353 • 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 were 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.	4.8% 17/353 • 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 were 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	4.5% 16/353 • 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 were 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.	2.3% 8/353 • 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 were 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.
Publication restrictions are in place

Restriction type: OTHER

Measure	UMEC/VI 62.5/25 µg QD n=353 participants at risk Participants were randomized to umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once-daily (QD) treatment in the morning via a dry powder inhaler (DPI) and placebo in the morning and evening via a separate DPI.	FSC 250/50 µg BID n=353 participants at risk Participants were randomized to fluticasone propionate/salmeterol (FSC) 250/50 µg twice-daily (BID) treatment in the morning and evening via a DPI and placebo in the morning via a separate DPI.
Infections and infestations Pneumonia	0.00% 0/353 • 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 were 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.	0.85% 3/353 • 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 were 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 Bronchitis	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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 Burn infection	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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 Gastroenteritis viral	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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 Infective exacerbation of chronic obstructive airways diseas	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.28% 1/353 • 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 were 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.	0.85% 3/353 • 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 were 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.
Respiratory, thoracic and mediastinal disorders Obstructive airways disorder	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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.
Injury, poisoning and procedural complications Head injury	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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.
Injury, poisoning and procedural complications Subdural haematoma	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian cancer	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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.
Nervous system disorders Ischaemic stroke	0.00% 0/353 • 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 were 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.	0.57% 2/353 • 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 were 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 Myocardial infarction	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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 Upper gastrointestinal haemorrhage	0.28% 1/353 • 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 were 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% 0/353 • 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 were 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.
Investigations Alanine aminotransferase increased	0.00% 0/353 • 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 were 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% 1/353 • 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 were 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.