Trial Outcomes & Findings for Evaluate the Efficacy and Safety of GSK573719 Delivered Via a Novel Dry Powder Inhaler in Subjects With COPD (NCT NCT01387230)

Last Updated: 2017-11-09

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, 14, 28, 56, 84, and 85. 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 85 is the mean of the FEV1 values obtained 23 and 24 hours after the morning dosing on Day 84). Change from Baseline was calculated as the trough FEV1 minus the 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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

206 participants

Primary outcome timeframe

Baseline and Day 85

Results posted on

2017-11-09

Participant Flow

Participants (par.) who met eligibility criteria at Screening (Visit 1) completed a 5- to 9-day run-in period and were then randomized to a 12-week treatment period. A total of 246 par. were screened; 206 par. who were eligible were randomized and 206 par. received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Placebo Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 12 weeks.	UMEC 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Overall Study STARTED	68	69	69
Overall Study COMPLETED	50	62	56
Overall Study NOT COMPLETED	18	7	13

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 12 weeks.	UMEC 62.5 µg QD Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg) QD via a DPI in the morning for 12 weeks.	UMEC 125 µg QD Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Overall Study Adverse Event	0	1	3
Overall Study Lack of Efficacy	8	5	4
Overall Study Protocol-defined Stopping Criteria	6	0	5
Overall Study Lost to Follow-up	0	0	1
Overall Study Withdrawal by Subject	4	1	0

Baseline Characteristics

Evaluate the Efficacy and Safety of GSK573719 Delivered Via a Novel Dry Powder Inhaler in Subjects With COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=68 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=69 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=69 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.	Total n=206 Participants Total of all reporting groups
Age, Continuous	62.5 Years STANDARD_DEVIATION 8.72 • n=93 Participants	62.3 Years STANDARD_DEVIATION 9.50 • n=4 Participants	64.6 Years STANDARD_DEVIATION 7.96 • n=27 Participants	63.1 Years STANDARD_DEVIATION 8.77 • n=483 Participants
Sex: Female, Male Female	26 Participants n=93 Participants	25 Participants n=4 Participants	27 Participants n=27 Participants	78 Participants n=483 Participants
Sex: Female, Male Male	42 Participants n=93 Participants	44 Participants n=4 Participants	42 Participants n=27 Participants	128 Participants n=483 Participants
Race/Ethnicity, Customized African American/African Heritage	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants
Race/Ethnicity, Customized Asian - Japanese Heritage	8 Participants n=93 Participants	7 Participants n=4 Participants	6 Participants n=27 Participants	21 Participants n=483 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	2 Participants n=483 Participants
Race/Ethnicity, Customized White - White/Caucasian/European Heritage	58 Participants n=93 Participants	60 Participants n=4 Participants	61 Participants n=27 Participants	179 Participants n=483 Participants

PRIMARY outcome

Timeframe: Baseline and Day 85

Population: Intent-to-Treat (ITT) Population: all randomized par. who received \>=1 dose of study drug. Par. analyzed are those with data available at the presented time point; but, all par. without missing covariate information and with \>=1 post-BL measurement were included in the analysis.

Outcome measures

Outcome measures
Measure	Placebo n=50 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=61 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=55 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85	-0.007 Liters Standard Error 0.0280	0.120 Liters Standard Error 0.0257	0.145 Liters Standard Error 0.0268

SECONDARY outcome

Timeframe: Baseline and Days 1, 28 and 84

Population: ITT Population. All participants with \>=1 post-BL assessment and non-missing covariate data are included in the analysis. Different participants may have been analyzed at different time points (represented by n=X, X, X in the category titles), so the overall number of participants analyzed reflects everyone in the ITT Population.

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, and Day 84 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 1 hour, 3 hours, and 6 hours. Change from Baseline was the WM minus Baseline. 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, center group, day, and day by Baseline and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=69 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=69 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) Day 1, n=66, 69, 69	0.017 Liters Standard Error 0.0150	0.141 Liters Standard Error 0.0147	0.164 Liters Standard Error 0.0147
Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) Day 28, n= 53, 65, 60	-0.024 Liters Standard Error 0.0223	0.141 Liters Standard Error 0.0206	0.172 Liters Standard Error 0.0212
Change From Baseline in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Days 1, 28 (Week 4) and 84 (Week 12) Day 84, n= 49, 60, 56	-0.003 Liters Standard Error 0.0271	0.163 Liters Standard Error 0.0248	0.188 Liters Standard Error 0.0256

SECONDARY outcome

Timeframe: Baseline, Day 1 and Day 84

Pulmonary function was measured by FEV1, defined as the maximal amount of air that can be forcefully exhaled in one second. Serial FEV1 measurements were taken electronically by spirometry. Serial FEV1 measurements of interest for Day 1 were collected at 1, 3, 6, 23 and 24 hours post-dose on Day 1 and for Day 84, the measures were pre-dose (24 hours post-dose of Day 83 morning dose but prior to Day 84's dose) and 1, 3, 6, 23 and 24 hours post dose on Day 84. Baseline is the mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1. Change from Baseline was calculated as FEV1 value at the evaluated time point minus Baseline. Analysis performed separately by Visit/Day using a repeated measures model with covariates of treatment, Baseline, smoking status, center group, time, time by Baseline and time by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=68 Participants Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=69 Participants Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=69 Participants Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 1, 1 hour, n=68, 69, 69	-0.001 Liters Standard Error 0.0148	0.132 Liters Standard Error 0.0147	0.142 Liters Standard Error 0.0147
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 1, 3 hours ,n=68, 69, 69	0.035 Liters Standard Error 0.0187	0.165 Liters Standard Error 0.0186	0.210 Liters Standard Error 0.0186
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 1, 6 hours, n=66, 69, 69	0.000 Liters Standard Error 0.0206	0.156 Liters Standard Error 0.0203	0.169 Liters Standard Error 0.0203
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 1, 23 hours, n=67, 69, 65	-0.027 Liters Standard Error 0.0178	0.070 Liters Standard Error 0.0176	0.113 Liters Standard Error 0.0180
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 1, 24 hours, n=67, 69, 66	-0.020 Liters Standard Error 0.0190	0.099 Liters Standard Error 0.0188	0.151 Liters Standard Error 0.0191
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, Pre-dose, n=50, 60, 56	0.002 Liters Standard Error 0.0299	0.155 Liters Standard Error 0.0269	0.177 Liters Standard Error 0.0283
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, 1 hour,n=50, 60, 56	-0.025 Liters Standard Error 0.0299	0.167 Liters Standard Error 0.0270	0.199 Liters Standard Error 0.0283
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, 3 hours, n=50, 61, 56	0.012 Liters Standard Error 0.0301	0.189 Liters Standard Error 0.0271	0.219 Liters Standard Error 0.0285
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, 6 hours,n=49, 61, 56	0.006 Liters Standard Error 0.0286	0.159 Liters Standard Error 0.0257	0.178 Liters Standard Error 0.0270
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, 23 hours, n=50, 60, 55	-0.019 Liters Standard Error 0.0301	0.106 Liters Standard Error 0.0271	0.142 Liters Standard Error 0.0286
Change From Baseline in Serial FEV1 Over 24 Hours Post-dose at Days 1 and 84 (Week 12) Day 84, 24 hours, n=50, 61, 55	0.020 Liters Standard Error 0.0299	0.142 Liters Standard Error 0.0269	0.170 Liters Standard Error 0.0284

Adverse Events

Placebo

Serious events: 1 serious events

Other events: 16 other events

Deaths: 0 deaths

UMEC 62.5 µg

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

UMEC 125 µg

Serious events: 2 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Placebo n=68 participants at risk Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=69 participants at risk Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=69 participants at risk Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Cardiac disorders Coronary artery stenosis	0.00% 0/68 • 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 12 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.	0.00% 0/69 • 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 12 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% 1/69 • 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 12 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 Non-cardiac chest pain	1.5% 1/68 • 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 12 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.	0.00% 0/69 • 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 12 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.	0.00% 0/69 • 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 12 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.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung neoplasm malignant	0.00% 0/68 • 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 12 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% 1/69 • 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 12 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.	0.00% 0/69 • 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 12 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 Chronic obstructive pulmonary disease	0.00% 0/68 • 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 12 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.	0.00% 0/69 • 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 12 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% 1/69 • 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 12 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.

Other adverse events

Other adverse events
Measure	Placebo n=68 participants at risk Participants received matching placebo QD via a DPI in the morning for 12 weeks.	UMEC 62.5 µg n=69 participants at risk Participants received UMEC 62.5 µg QD via a DPI in the morning for 12 weeks.	UMEC 125 µg n=69 participants at risk Participants received UMEC 125 µg QD via a DPI in the morning for 12 weeks.
Infections and infestations Nasopharyngitis	10.3% 7/68 • 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 12 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.	11.6% 8/69 • 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 12 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% 7/69 • 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 12 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	10.3% 7/68 • 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 12 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% 5/69 • 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 12 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.	14.5% 10/69 • 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 12 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	5.9% 4/68 • 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 12 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.	2.9% 2/69 • 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 12 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.	0.00% 0/69 • 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 12 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	1.5% 1/68 • 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 12 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.	0.00% 0/69 • 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 12 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% 5/69 • 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 12 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