Trial Outcomes & Findings for A 24-week Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo in Subjects With COPD (NCT NCT01636713)

Last Updated: 2017-01-09

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, 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 FEV1at that visit minus Baseline. Analysis was performed using a repeated measures model with covariates of treatment, Baseline, smoking status, country/region, day, day by Baseline and day by treatment interactions. par.=participants.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

581 participants

Primary outcome timeframe

Baseline and Day 169

Results posted on

2017-01-09

Participant Flow

Participants who met eligibility criteria at Screening (Visit 1) completed a 7 to 14-day run-in period and were then randomized to a 24-week treatment period.

A total of 739 participants were screened; 580 participants were randomized in a 1:1:1 ratio to receive either one of the active treatments or placebo. One participant was randomized but data was excluded from analysis as requested by the local Ethic Committee because the participant was not consented according to the GCP standards.

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/VI 62.5/25 µg QD Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning 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	193	194	193
Overall Study COMPLETED	161	166	170
Overall Study NOT COMPLETED	32	28	23

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/VI 62.5/25 µg QD Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning 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	16	16	7
Overall Study Lack of Efficacy	6	6	2
Overall Study Protocol Violation	3	0	1
Overall Study Lost to Follow-up	0	0	1
Overall Study Withdrawal by Subject	5	4	8
Overall Study Met Protocol-defined Stopping Criteria	2	2	4

Baseline Characteristics

A 24-week Study to Evaluate the Efficacy and Safety of GSK573719/GW642444 125/25 mcg and 62.5/25mcg Inhalation Powder Compared With Placebo in Subjects With COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=193 Participants Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC/VI 62.5/25 µg QD n=194 Participants Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning for 24 weeks.	UMEC/VI 125/25 µg QD n=193 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.	Total n=580 Participants Total of all reporting groups
Age, Continuous	64.3 Years STANDARD_DEVIATION 8.78 • n=5 Participants	64.0 Years STANDARD_DEVIATION 8.71 • n=7 Participants	63.7 Years STANDARD_DEVIATION 8.26 • n=5 Participants	64.0 Years STANDARD_DEVIATION 8.57 • n=4 Participants
Gender Female	16 Participants n=5 Participants	11 Participants n=7 Participants	11 Participants n=5 Participants	38 Participants n=4 Participants
Gender Male	177 Participants n=5 Participants	183 Participants n=7 Participants	182 Participants n=5 Participants	542 Participants n=4 Participants
Race/Ethnicity, Customized Asian-East Asian Heritage	170 Participants n=5 Participants	173 Participants n=7 Participants	173 Participants n=5 Participants	516 Participants n=4 Participants
Race/Ethnicity, Customized Asian-South East Asian Heritage	21 Participants n=5 Participants	21 Participants n=7 Participants	20 Participants n=5 Participants	62 Participants n=4 Participants
Race/Ethnicity, Customized Asian-Mixed Asian Heritage	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 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=162 Participants Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC/VI 62.5/25 µg QD n=165 Participants Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning for 24 weeks.	UMEC/VI 125/25 µg QD n=168 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)	1.040 Liters Standard Error 0.0147	1.191 Liters Standard Error 0.0146	1.256 Liters Standard Error 0.0146

SECONDARY outcome

Timeframe: Day 168 (Week 24)

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, country/region, day, day by Baseline dyspnea index (BDI) focal score and day by treatment interactions.

Outcome measures

Outcome measures
Measure	Placebo n=162 Participants Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC/VI 62.5/25 µg QD n=162 Participants Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning for 24 weeks.	UMEC/VI 125/25 µg QD n=168 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Transition Dyspnea Index (TDI) Focal Score at Day 168 (Week 24)	2.0 Scores on a scale Standard Error 0.20	2.7 Scores on a scale Standard Error 0.20	2.9 Scores on a scale Standard Error 0.20

SECONDARY outcome

Timeframe: Baseline and Day 1

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 using the 0-6-hour post-dose FEV1 measurements collected on Day 1, which included pre-dose (30 minutes \[min\] and 5 min prior to dosing) and post-dose at 15 min, 30 min, 1 hour, 3 hours, and 6 hours. Change from Baseline at Day 1was calculated as the WM at post -dose value on Day 1 minus Baseline (mean of the two assessments made 30 min and 5 min pre-dose on Day 1). Analysis was performed using an Analysis of Covariance (ANCOVA) model with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 and 5 minutes pre-dose on Day 1), smoking status, and country/region.

Outcome measures

Outcome measures
Measure	Placebo n=190 Participants Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC/VI 62.5/25 µg QD n=192 Participants Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning for 24 weeks.	UMEC/VI 125/25 µg QD n=192 Participants Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Change From Baseline Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 1	0.015 Liters Standard Error 0.0075	0.174 Liters Standard Error 0.0075	0.197 Liters Standard Error 0.0075

Adverse Events

Placebo

Serious events: 17 serious events

Other events: 31 other events

Deaths: 0 deaths

UMEC/VI 62.5/25 µg QD

Serious events: 15 serious events

Other events: 38 other events

Deaths: 0 deaths

UMEC/VI 125/25 µg QD

Serious events: 6 serious events

Other events: 33 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=193 participants at risk Participants received matching placebo once daily (QD) via a dry powder inhaler (DPI) in the morning for 24 weeks.	UMEC/VI 62.5/25 µg QD n=194 participants at risk Participants received umeclidinium bromide (UMEC)/vilanterol (VI) 62.5/25 micrograms (µg) QD via a DPI in the morning for 24 weeks.	UMEC/VI 125/25 µg QD n=193 participants at risk Participants received UMEC/VI 125/25 µg QD via a DPI in the morning for 24 weeks.
Infections and infestations Nasopharyngitis	9.3% 18/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	8.8% 17/194 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	9.3% 18/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.
Infections and infestations Upper respiratory tract infection	5.7% 11/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	9.8% 19/194 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	6.7% 13/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.
Respiratory, thoracic and mediastinal disorders Cough	2.1% 4/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	3.1% 6/194 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.	2.1% 4/193 • 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). On-treatment SAEs and non-serious AEs are reported for members of the ITT Population, comprising all participants randomized to treatment who received at least one dose of randomized study medication during the treatment period.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
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