Trial Outcomes & Findings for The Purpose of This Study is to Evaluate the Spirometric Effect (Trough FEV1) of Umeclidinium/Vilanterol 62.5/25 mcg Once Daily Compared With Tiotriopium 18 mcg Once Daily Over a 24-week Treatment Period in Subjects With COPD (NCT NCT01777334)

Last Updated: 2018-01-24

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, 140, 168, and 169. Baseline is defined as the mean of the assessments made 30 minutes (min) pre-dose and 5 min pre-dose on Treatment Day 1. Trough FEV1 is defined as the mean of the FEV1 values obtained at 23 and 24 hours (hr) after the previous morning's dosing (ie., trough FEV1 on Day 169 is the mean of the FEV1 values obtained 23 and 24 hr after the morning dosing on Day 168). Change from Baseline at a particular visit was calculated as the trough FEV1 value at that visit minus the Baseline value. Analysis was performed using a repeated measures model with covariates of treatment, Baseline (mean of the two assessmentsmade 30 min and 5 min pre-dose on Day 1), smoking status, center group, day, and day by Baseline and day by treatment interactions.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

905 participants

Primary outcome timeframe

Baseline and Day 169

Results posted on

2018-01-24

Participant Flow

Participants (par.) who met the eligibility criteria at Screening (Visit 1) completed a 7- to 10-day Run-in Period and entered a 24-week Treatment Period. 1191 par. signed the informed consent form and were assigned subject numbers, 1053 par. were screened and 905 par. were randomized and received at least one dose of study medication.

Participant milestones

Participant milestones
Measure	UMEC/VI 62.5/25 µg Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.
Overall Study STARTED	454	451
Overall Study COMPLETED	401	388
Overall Study NOT COMPLETED	53	63

Reasons for withdrawal

Reasons for withdrawal
Measure	UMEC/VI 62.5/25 µg Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.
Overall Study Adverse Event	18	14
Overall Study Lack of Efficacy	15	29
Overall Study Protocol Violation	3	7
Overall Study Lost to Follow-up	3	2
Overall Study Withdrawal by Subject	14	11

Baseline Characteristics

The Purpose of This Study is to Evaluate the Spirometric Effect (Trough FEV1) of Umeclidinium/Vilanterol 62.5/25 mcg Once Daily Compared With Tiotriopium 18 mcg Once Daily Over a 24-week Treatment Period in Subjects With COPD

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	UMEC/VI 62.5/25 µg n=454 Participants Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg n=451 Participants Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.	Total n=905 Participants Total of all reporting groups
Age, Continuous	61.9 Years STANDARD_DEVIATION 8.41 • n=5 Participants	62.7 Years STANDARD_DEVIATION 8.50 • n=7 Participants	62.3 Years STANDARD_DEVIATION 8.46 • n=5 Participants
Sex: Female, Male Female	144 Participants n=5 Participants	148 Participants n=7 Participants	292 Participants n=5 Participants
Sex: Female, Male Male	310 Participants n=5 Participants	303 Participants n=7 Participants	613 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian/European Heritage	438 Participants n=5 Participants	442 Participants n=7 Participants	880 Participants n=5 Participants
Race/Ethnicity, Customized African American/African Heritage	13 Participants n=5 Participants	7 Participants n=7 Participants	20 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race/Ethnicity, Customized White - Arabic/North African Heritage	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Mixed Race	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Day 169

Population: Intent-to-Treat (ITT) Population: all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period. 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	UMEC/VI 62.5/25 µg n=400 Participants Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg n=388 Participants Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.
Change From Baseline (BL) in Trough Forced Expiratory Volume in One Second (FEV1) on Day 169 (Week 24)	0.205 Liters Standard Error 0.0114	0.093 Liters Standard Error 0.0115

SECONDARY outcome

Timeframe: Baseline and Day 168

Population: ITT Population. Par. analyzed are those with data available at the presented time point; but, all par. without missing covariate information and with \>=1 post-Baseline measurement were included in the analysis.

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, 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 BL at a particular visit was calculated as the WM value at that visit minus the BL value. Analysis was performed using a repeated measures model with covariates of treatment, BL (mean of the two assessments made 30 min and 5 min pre-dose on Day 1), smoking status, center group, day, and day by BL and day by treatment interactions.

Outcome measures

Outcome measures
Measure	UMEC/VI 62.5/25 µg n=404 Participants Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg n=387 Participants Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.
Change From Baseline (BL) in Weighted Mean (WM) 0-6 Hour FEV1 Obtained Post-dose at Day 168	0.276 Liters Standard Error 0.0124	0.170 Liters Standard Error 0.0126

Adverse Events

UMEC/VI 62.5/25 µg

Serious events: 16 serious events

Other events: 71 other events

Deaths: 0 deaths

TIO 18 µg

Serious events: 17 serious events

Other events: 72 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	UMEC/VI 62.5/25 µg n=454 participants at risk Participants received umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 micrograms (µg) once daily (QD) each morning via a dry powder inhaler (DPI) and placebo QD each morning via a DPI for 24 weeks.	TIO 18 µg n=451 participants at risk Participants received tiotropium (TIO) 18 µg QD each morning via a DPI and placebo QD each morning via a DPI for 24 weeks.
Nervous system disorders Headache	8.8% 40/454 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period.	6.9% 31/451 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period.
Infections and infestations Nasopharyngitis	6.2% 28/454 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period.	6.7% 30/451 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period.
Respiratory, thoracic and mediastinal disorders Cough	2.9% 13/454 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug during the Treatment Period.	3.3% 15/451 • On-treatment serious adverse events (SAEs) and non-serious AEs were collected from the start of study medication until the end of treatment (up to 24 weeks). SAEs and non-serious AEs are reported for members of the ITT Population, comprised of all participants randomized to treatment who received at least one dose of randomized study drug 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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