Trial Outcomes & Findings for A 24-week Evaluation of GSK573719/Vilanterol (62.5/25mcg) and Components in COPD (NCT NCT01313650)

Last Updated: 2018-08-06

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. 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

1538 participants

Primary outcome timeframe

Baseline and Day 169

Results posted on

2018-08-06

Participant Flow

Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 7 to 10-day run-in period and were then randomized to a 24-week treatment (trt.) period. A total of 2210 participants were screened; 1536 participants were randomized and 1532 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 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 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 62.5/25 µg QD Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 24 weeks.
Overall Study STARTED	280	418	421	413
Overall Study COMPLETED	204	324	318	332
Overall Study NOT COMPLETED	76	94	103	81

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 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 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 62.5/25 µg QD Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 24 weeks.
Overall Study Adverse Event	9	34	24	23
Overall Study Lack of Efficacy	37	20	32	20
Overall Study Lost to Follow-up	1	0	3	2
Overall Study Withdrawal by Subject	16	20	15	15
Overall Study Protocol Violation	4	7	5	6
Overall Study Met Protocol-defined Stopping Criteria	9	13	24	15

Baseline Characteristics

A 24-week Evaluation of GSK573719/Vilanterol (62.5/25mcg) and Components in COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=280 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=418 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=421 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=413 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 24 weeks.	Total n=1532 Participants Total of all reporting groups
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	1 Participants n=36 Participants
Age, Continuous	62.2 Years STANDARD_DEVIATION 9.04 • n=93 Participants	64.0 Years STANDARD_DEVIATION 9.16 • n=4 Participants	62.7 Years STANDARD_DEVIATION 8.52 • n=27 Participants	63.1 Years STANDARD_DEVIATION 8.71 • n=483 Participants	63.1 Years STANDARD_DEVIATION 8.86 • n=36 Participants
Sex: Female, Male Female	85 Participants n=93 Participants	120 Participants n=4 Participants	136 Participants n=27 Participants	108 Participants n=483 Participants	449 Participants n=36 Participants
Sex: Female, Male Male	195 Participants n=93 Participants	298 Participants n=4 Participants	285 Participants n=27 Participants	305 Participants n=483 Participants	1083 Participants n=36 Participants
Race/Ethnicity, Customized African American/African Heritage	9 Participants n=93 Participants	14 Participants n=4 Participants	9 Participants n=27 Participants	15 Participants n=483 Participants	47 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants	0 Participants n=483 Participants	9 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	1 Participants n=483 Participants	2 Participants n=36 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	1 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	1 Participants n=483 Participants	6 Participants n=36 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	12 Participants n=93 Participants	18 Participants n=4 Participants	18 Participants n=27 Participants	20 Participants n=483 Participants	68 Participants n=36 Participants
Race/Ethnicity, Customized Asian - South East Asian Heritage	9 Participants n=93 Participants	15 Participants n=4 Participants	13 Participants n=27 Participants	13 Participants n=483 Participants	50 Participants n=36 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	237 Participants n=93 Participants	354 Participants n=4 Participants	363 Participants n=27 Participants	348 Participants n=483 Participants	1302 Participants n=36 Participants
Race/Ethnicity, Customized White - Mixed Race	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 Mixed Race	11 Participants n=93 Participants	12 Participants n=4 Participants	9 Participants n=27 Participants	14 Participants n=483 Participants	46 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=201 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=322 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=317 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=330 Participants Participants received UMEC/VI 62.5/25 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)	0.004 Liters Standard Error 0.0158	0.119 Liters Standard Error 0.0126	0.076 Liters Standard Error 0.0127	0.171 Liters Standard Error 0.0126

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=204 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=326 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=317 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=336 Participants Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 24 weeks.
Mean Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24)	1.2 Scores on a scale Standard Error 0.20	2.2 Scores on a scale Standard Error 0.16	2.1 Scores on a scale Standard Error 0.16	2.4 Scores on a scale Standard Error 0.16

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=206 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=319 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=311 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=333 Participants Participants received UMEC/VI 62.5/25 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	0.001 Liters Standard Error 0.0158	0.151 Liters Standard Error 0.0128	0.123 Liters Standard Error 0.0128	0.243 Liters Standard Error 0.0127

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=125 Participants Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=209 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=202 Participants Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=230 Participants Participants received UMEC/VI 62.5/25 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	-0.06 Scores on a scale Standard Error 0.037	-0.16 Scores on a scale Standard Error 0.029	-0.21 Scores on a scale Standard Error 0.030	-0.23 Scores on a scale Standard Error 0.029

Adverse Events

Placebo

Serious events: 9 serious events

Other events: 62 other events

Deaths: 0 deaths

UMEC 62.5 µg QD

Serious events: 27 serious events

Other events: 96 other events

Deaths: 0 deaths

VI 25 µg QD

Serious events: 24 serious events

Other events: 87 other events

Deaths: 0 deaths

UMEC/VI 62.5/25 µg QD

Serious events: 21 serious events

Other events: 93 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=280 participants at risk Participants received matching placebo QD via a DPI in the morning for 24 weeks.	UMEC 62.5 µg QD n=418 participants at risk Participants received UMEC 62.5 µg QD via a DPI in the morning for 24 weeks.	VI 25 µg QD n=421 participants at risk Participants received VI 25 µg QD via a DPI for 24 weeks.	UMEC/VI 62.5/25 µg QD n=413 participants at risk Participants received UMEC/VI 62.5/25 µg QD via a DPI in the morning for 24 weeks.
Infections and infestations Nasopharyngitis	5.7% 16/280 • 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.	6.9% 29/418 • 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.	6.2% 26/421 • 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.	9.4% 39/413 • 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.
Infections and infestations Upper respiratory tract infection	5.0% 14/280 • 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.	5.0% 21/418 • 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.	4.0% 17/421 • 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.	3.1% 13/413 • 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	9.3% 26/280 • 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.	7.7% 32/418 • 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.	5.9% 25/421 • 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.	8.5% 35/413 • 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	2.5% 7/280 • 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.	3.8% 16/418 • 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.	3.6% 15/421 • 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.	1.5% 6/413 • 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 Oropharyngeal pain	1.4% 4/280 • 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.	1.4% 6/418 • 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.	3.3% 14/421 • 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.	3.1% 13/413 • 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	2.5% 7/280 • 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.	1.9% 8/418 • 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.	1.7% 7/421 • 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.	3.1% 13/413 • 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

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