Trial Outcomes & Findings for A 24-week Evaluation of GSK573719/Vilanterol (125/25mcg) and Components in COPD (NCT NCT01313637)

Last Updated: 2018-01-29

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. Trough FEV1 measurements were taken electronically by spirometry on Days 2, 28, 56, 84, 112, 168, and 169. Baseline is defined as the mean of the 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 at 23 and 24 hours after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline , smoking status, center group, day, and day by Baseline and day by treatment interactions. ITT=Intent-to-Treat; par.=participants.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1493 participants

Primary outcome timeframe

Baseline and Day 169

Results posted on

2018-01-29

Participant Flow

Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 7- to14-day run-in period and were then randomized to a 24-week treatment (trt.) period. A total of 2114 participants were screened; 1493 participants were randomized, and 1489 participants took at least one dose of randomized medication.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC 125 µg QD Participants received umeclidinium bromide (UMEC) 125 micrograms (µg) QD via a DPI in the morning for 24 weeks.	VI 25 µg QD Participants received vilanterol (VI) 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg QD Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Overall Study STARTED	275	407	404	403
Overall Study COMPLETED	183	312	298	325
Overall Study NOT COMPLETED	92	95	106	78

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC 125 µg QD Participants received umeclidinium bromide (UMEC) 125 micrograms (µg) QD via a DPI in the morning for 24 weeks.	VI 25 µg QD Participants received vilanterol (VI) 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg QD Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Overall Study Adverse Event	17	24	25	18
Overall Study Lack of Efficacy	44	38	37	24
Overall Study Protocol Violation	4	3	11	5
Overall Study Met Protocol- Defined Stopping Criteria	16	15	14	13
Overall Study Lost to Follow-up	0	2	1	3
Overall Study Withdrawal by Subject	11	13	18	15

Baseline Characteristics

A 24-week Evaluation of GSK573719/Vilanterol (125/25mcg) and Components in COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=275 Participants Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC 125 µg n=407 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=404 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=403 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.	Total n=1489 Participants Total of all reporting groups
Age, Continuous	62.2 Years STANDARD_DEVIATION 8.53 • n=93 Participants	63.1 Years STANDARD_DEVIATION 8.48 • n=4 Participants	62.8 Years STANDARD_DEVIATION 8.80 • n=27 Participants	63.4 Years STANDARD_DEVIATION 8.08 • n=483 Participants	62.9 Years STANDARD_DEVIATION 8.47 • n=36 Participants
Sex: Female, Male Female	100 Participants n=93 Participants	137 Participants n=4 Participants	139 Participants n=27 Participants	139 Participants n=483 Participants	515 Participants n=36 Participants
Sex: Female, Male Male	175 Participants n=93 Participants	270 Participants n=4 Participants	265 Participants n=27 Participants	264 Participants n=483 Participants	974 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	9 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants	4 Participants n=483 Participants	24 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants
Race/Ethnicity, Customized Asian - Central/South Asian Heritage	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	13 Participants n=93 Participants	21 Participants n=4 Participants	21 Participants n=27 Participants	19 Participants n=483 Participants	74 Participants n=36 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	14 Participants n=93 Participants	19 Participants n=4 Participants	20 Participants n=27 Participants	20 Participants n=483 Participants	73 Participants n=36 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	4 Participants n=36 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	237 Participants n=93 Participants	361 Participants n=4 Participants	353 Participants n=27 Participants	359 Participants n=483 Participants	1310 Participants n=36 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants

PRIMARY outcome

Timeframe: Baseline and Day 169

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

Outcome measures

Outcome measures
Measure	Placebo n=182 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 125 µg n=312 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=299 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=323 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)	-0.031 Liters Standard Error 0.0153	0.129 Liters Standard Error 0.0119	0.093 Liters Standard Error 0.0121	0.207 Liters Standard Error 0.0119

SECONDARY outcome

Timeframe: Day 168 (Week 24)

Considered an 'other' endpoint by the FDA. The TDI is an interviewer-administered instrument which measures the changes in the participant's dyspnea from Baseline. This questionnaire was collected on Days 28, 84 and 168. The scores in the TDI evaluate ratings for 3 different categories (functional impairment, magnitude of task in exertional capacity, and magnitude of effort). TDI scores ranged from -3 (major deterioration) to +3 (major improvement); total score = -9 to 9. Analysis was performed using a repeated measures model with covariates of treatment, Baseline dyspnea index (BDI) focal score,smoking status, center group, day, day by BDI focal score and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=186 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 125 µg n=313 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=294 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=324 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Mean Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24)	0.8 Scores on a scale Standard Error 0.20	1.2 Scores on a scale Standard Error 0.16	1.3 Scores on a scale Standard Error 0.16	1.8 Scores on a scale Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline and Day 168

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 WM FEV1 was derived by calculating the area under the FEV1/time curve (AUC) using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. The WM was calculated at Days 1, 28, 84, and 168 using the 0-6-hour post-dose FEV1 measurements collected on that day, which included pre-dose (Day 1: 30 minutes \[min\] and 5 min prior to dosing; other serial visits: 23 and 24 hours after the previous morning dose) and post-dose at 15 min, 30 min, 1 hour, 3 hours, and 6 hours. Change from Baseline at a particular visit was calculated as the WM at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessments made 30 min and 5 min pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=180 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 125 µg n=311 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=298 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=316 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 168	-0.018 Liters Standard Error 0.0150	0.160 Liters Standard Error 0.0118	0.127 Liters Standard Error 0.0119	0.269 Liters Standard Error 0.0118

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and Week 24

The newly developed SOBDA questionnaire assesses dyspnea or shortness of breath (SOB) with daily activities. The SOBDA questionnaire is made up of 13 items completed by the participant (par.) each evening prior to bedtime, when the par. is instructed to reflect on the current day's activities. The daily score is computed as the mean of the scores on the 13 items (\>=7 items must have non-missing responses for this to be calculated). The par. is assigned a weekly mean SOBDA score ranging from 1 to 4 (greater scores indicate more severe breathlessness with daily activities) based on the mean of 7 days of data (\>=4 of 7 days must be completed for a weekly mean to be calculated). Change from BL is the mean weekly SOBDA score minus BL. Analysis was performed using MMRM with covariates of treatment, BL (mean score in the week prior to treatment), smoking status, center group, week, week by BL and week by treatment interactions. This MMRM analysis only included Weeks 4, 8, 12, and 24.

Outcome measures

Outcome measures
Measure	Placebo n=118 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 125 µg n=215 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=212 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=234 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Change From Baseline in the Mean Shortness of Breath With Daily Activities (SOBDA) Score for Week 24	-0.07 Scores on a scale Standard Error 0.038	-0.15 Scores on a scale Standard Error 0.029	-0.10 Scores on a scale Standard Error 0.029	-0.22 Scores on a scale Standard Error 0.029

Adverse Events

Placebo

Serious events: 17 serious events

Other events: 63 other events

Deaths: 0 deaths

UMEC 125 µg

Serious events: 22 serious events

Other events: 97 other events

Deaths: 0 deaths

VI 25 µg

Serious events: 20 serious events

Other events: 113 other events

Deaths: 0 deaths

UMEC/VI 125/25 µg

Serious events: 23 serious events

Other events: 102 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=275 participants at risk Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 125 µg n=407 participants at risk Participants received UMEC 125 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg n=404 participants at risk Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 125/25 µg n=403 participants at risk Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Infections and infestations Nasopharyngitis	11.6% 32/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	9.1% 37/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	13.6% 55/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	11.7% 47/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
Nervous system disorders Headache	11.3% 31/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	9.1% 37/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	10.1% 41/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	10.2% 41/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
Respiratory, thoracic and mediastinal disorders Cough	5.8% 16/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	3.7% 15/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	4.5% 18/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	7.2% 29/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
Respiratory, thoracic and mediastinal disorders Dyspnoea	3.3% 9/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	1.2% 5/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	2.5% 10/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	0.99% 4/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
Musculoskeletal and connective tissue disorders Back pain	4.7% 13/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	4.2% 17/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	2.5% 10/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	2.5% 10/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.
General disorders Pyrexia	2.5% 7/275 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	2.2% 9/407 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	2.2% 9/404 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.	3.2% 13/403 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs were collected in members of the ITT Population, comprised of all participants who had received at least one dose of randomized study medication during treatment period.

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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