Trial Outcomes & Findings for A Study to Evaluate the Effect of the Combination of Umeclidinium (UMEC) and Vilanterol (VI) on Exercise Endurance Time (EET) in Participants With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02275052)
NCT ID: NCT02275052
Last Updated: 2018-08-16
Results Overview
EET post-dose at W12 is defined as the EET obtained 3 hours after dosing at W12. EET was measured using the externally paced field walking test called endurance shuttle walk test (ESWT). Change from BL in EET at W12 was analyzed using a repeated measures model with covariates of period walking speed, mean walking speed, period, trt, visit (Day 2, W6 and W12), smoking status, visit by period walking speed, visit by mean walking speed and visit by trt interactions. BL was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each par. is the mean of the levels used for the ESWT in each of the two trt periods. Period walking speed for each par. and trt period is the difference between the level for that par. and period and the mean walking speed for that par. Intent-to-treat (ITT) Population: all randomized par., excluding those who were randomized in error, and par. who discontinued trt (off-trt).
COMPLETED
PHASE4
198 participants
Baseline (BL) and at Week (W) 12 of each treatment (trt) period (up to Week 30)
2018-08-16
Participant Flow
Participants (par.) who met the eligibility criteria at screening, entered the 11- to 25-day Run-in period followed by two 12-week Double-blind treatment periods that were separated by 12- to 17-day washout period. The total duration of participation, including the follow-up, was approximately 30 weeks.
A total of 374 par. were screened, of these, 10 par. were pre-screen failures, 132 par. were screen failures and 34 par. were run-in failures; 198 par. who were randomized into the study and received treatment were included in the Intent-to-Treat (ITT) Population.
Participant milestones
| Measure |
Placebo Then UMEC/VI 62.5/25 µg
Participants received Placebo and then umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 micrograms (µg)/25 µg each morning (once daily) as one inhalation via the Dry Powder Inhaler (DPI) for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
UMEC/VI 62.5/25 µg Then Placebo
Participants received UMEC/ VI 62.5 µg/25 µg and then placebo each morning (once daily) as one inhalation via the DPI for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Period 2: UMEC/VI 62.5/25 µg Then Placebo
Participants received UMEC/VI 62.5 µg/25 µg and then Placebo each morning (once daily) as one inhalation via the Dry Powder Inhaler (DPI) for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Period 2: Placebo Then UMEC/VI 62.5/25 µg
Participants received placebo and then UMEC/VI 62.5 µg/25 µg each morning (once daily) as one inhalation via the DPI for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|---|---|
|
Period 1: Treatment Period 1 (12 Weeks)
STARTED
|
99
|
99
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
COMPLETED
|
90
|
93
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
NOT COMPLETED
|
9
|
6
|
0
|
0
|
|
Washout Period (12-17 Days)
STARTED
|
90
|
93
|
0
|
0
|
|
Washout Period (12-17 Days)
COMPLETED
|
86
|
93
|
0
|
0
|
|
Washout Period (12-17 Days)
NOT COMPLETED
|
4
|
0
|
0
|
0
|
|
Period 2: Treatment Period 2 (12 Weeks)
STARTED
|
0
|
0
|
93
|
86
|
|
Period 2: Treatment Period 2 (12 Weeks)
COMPLETED
|
0
|
0
|
88
|
72
|
|
Period 2: Treatment Period 2 (12 Weeks)
NOT COMPLETED
|
0
|
0
|
5
|
14
|
Reasons for withdrawal
| Measure |
Placebo Then UMEC/VI 62.5/25 µg
Participants received Placebo and then umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 micrograms (µg)/25 µg each morning (once daily) as one inhalation via the Dry Powder Inhaler (DPI) for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
UMEC/VI 62.5/25 µg Then Placebo
Participants received UMEC/ VI 62.5 µg/25 µg and then placebo each morning (once daily) as one inhalation via the DPI for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Period 2: UMEC/VI 62.5/25 µg Then Placebo
Participants received UMEC/VI 62.5 µg/25 µg and then Placebo each morning (once daily) as one inhalation via the Dry Powder Inhaler (DPI) for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Period 2: Placebo Then UMEC/VI 62.5/25 µg
Participants received placebo and then UMEC/VI 62.5 µg/25 µg each morning (once daily) as one inhalation via the DPI for 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|---|---|
|
Period 1: Treatment Period 1 (12 Weeks)
Lost to Follow-up
|
0
|
1
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
Met protocol-defined stopping criteria
|
0
|
1
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
Withdrawal by Subject
|
6
|
4
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
Physician Decision
|
1
|
0
|
0
|
0
|
|
Period 1: Treatment Period 1 (12 Weeks)
Adverse Event
|
2
|
0
|
0
|
0
|
|
Washout Period (12-17 Days)
Withdrawal by Subject
|
3
|
0
|
0
|
0
|
|
Washout Period (12-17 Days)
Lack of Efficacy
|
1
|
0
|
0
|
0
|
|
Period 2: Treatment Period 2 (12 Weeks)
Adverse Event
|
0
|
0
|
3
|
2
|
|
Period 2: Treatment Period 2 (12 Weeks)
Withdrawal by Subject
|
0
|
0
|
1
|
4
|
|
Period 2: Treatment Period 2 (12 Weeks)
Lack of Efficacy
|
0
|
0
|
1
|
6
|
|
Period 2: Treatment Period 2 (12 Weeks)
Met Protocol-defined Stopping Criteria
|
0
|
0
|
0
|
2
|
Baseline Characteristics
A Study to Evaluate the Effect of the Combination of Umeclidinium (UMEC) and Vilanterol (VI) on Exercise Endurance Time (EET) in Participants With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
UMEC/VI 62.5/25 mcg and Placebo in One of the Two Sequences
n=198 Participants
Par. received a sequence consisting of the following 2 treatments: One inhalation of UMEC/VI 62.5/25 mcg or placebo once daily using a DPI. Each treatment was self-administered in the morning for 12 weeks. The treatments were separated by a 12 to 17 day washout period; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|
|
Age, Continuous
|
60.7 Years
STANDARD_DEVIATION 9.47 • n=5 Participants
|
|
Sex: Female, Male
Female
|
94 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
104 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American/African Heritage
|
19 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White-White/Caucasian/European Heritage
|
179 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline (BL) and at Week (W) 12 of each treatment (trt) period (up to Week 30)Population: ITT Population including off-treatment data. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
EET post-dose at W12 is defined as the EET obtained 3 hours after dosing at W12. EET was measured using the externally paced field walking test called endurance shuttle walk test (ESWT). Change from BL in EET at W12 was analyzed using a repeated measures model with covariates of period walking speed, mean walking speed, period, trt, visit (Day 2, W6 and W12), smoking status, visit by period walking speed, visit by mean walking speed and visit by trt interactions. BL was the EET assessment obtained prior to dosing on Day 1 of each period. The mean walking speed for each par. is the mean of the levels used for the ESWT in each of the two trt periods. Period walking speed for each par. and trt period is the difference between the level for that par. and period and the mean walking speed for that par. Intent-to-treat (ITT) Population: all randomized par., excluding those who were randomized in error, and par. who discontinued trt (off-trt).
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=172 Participants
Participants received umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 mcg/25 mcg each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Placebo
n=157 Participants
Participants received placebo each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|
|
Change From Baseline in Exercise Endurance Time (EET) Post-dose at Week 12 of Each Treatment Period
|
-2.06 Seconds (s)
Standard Error 9.286
|
-5.37 Seconds (s)
Standard Error 9.680
|
SECONDARY outcome
Timeframe: Baseline and at Week 12 of each treatment period (up to Week 30)Population: ITT Population including off-treatment data. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
Trough FEV1 is a measure of lung function and is defined as the mean of FEV1 values obtained 23 and 24 hours after dosing on the previous day. Trough FEV1 measurements were taken electronically by spirometry on Day 2, Week 6 and Week 12. Baseline was the assessment recorded before dosing on Day 1 of each period. Mean Baseline is the mean of the Baselines for each participant. Period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. Analysis was performed using a repeated measures model and the following covariates were included: period Baseline, mean Baseline, period, treatment, visit, smoking status, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=175 Participants
Participants received umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 mcg/25 mcg each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Placebo
n=164 Participants
Participants received placebo each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Week 12 of Each Treatment Period
|
0.173 Liters
Standard Error 0.0152
|
-0.034 Liters
Standard Error 0.0156
|
SECONDARY outcome
Timeframe: Baseline and at Week 12 of each treatment period (up to Week 30)Population: ITT Population including off-treatment data. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
FRC is defined as the amount of air still left in the lungs after breathing out normally. Standard body plethysmography techniques were used for lung volumes. Baseline is the assessment recorded before dosing on Day 1 of each period. Mean Baseline is the mean of the Baselines for each participant. Period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each participant. FRC 3 hours post-dose was measured from the value obtained 3 hours after dosing on Day 2 and Week 12. Analysis was performed using a repeated measures model and the following covariates were included: period Baseline, mean Baseline, period, treatment, visit, smoking status, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=178 Participants
Participants received umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 mcg/25 mcg each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Placebo
n=162 Participants
Participants received placebo each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|
|
Change From Baseline in Functional Residual Capacity (FRC) 3 Hours Post-dose at Week 12 of Each Treatment Period
|
-0.457 Liters
Standard Error 0.0531
|
-0.111 Liters
Standard Error 0.0557
|
SECONDARY outcome
Timeframe: Baseline and at Week 12 of each treatment period (up to Week 30)Population: ITT Population including off-treatment data. Number of par. represent those with data available at the time point; however, all par. in the ITT population without missing covariate information and with at least one post Baseline measurement are included.
IC is defined as the maximum amount of air that can be inhaled into the lungs from the normal resting position after breathing out normally. Standard body plethysmography techniques were used for lung volumes. Baseline is the IC value recorded pre-dose on Day 1 of each treatment period. Mean Baseline is the mean of the Baselines for each par. Period Baseline is the difference between the Baseline and the mean Baseline in each treatment period for each par. IC 3-hours post-dose was measured from the value obtained 3 hours after dosing on Day 2 and Week 12. Analysis performed using a repeated measures model with covariates of period Baseline, mean Baseline, period, treatment, visit (Day 2 or Week 12), smoking status, visit by period Baseline, visit by mean Baseline and visit by treatment interactions.
Outcome measures
| Measure |
UMEC/VI 62.5/25 mcg
n=178 Participants
Participants received umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 mcg/25 mcg each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Placebo
n=162 Participants
Participants received placebo each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|
|
Change From Baseline in Inspiratory Capacity (IC) 3 Hours Post-dose at Week 12 of Each Treatment Period
|
0.225 Liters
Standard Error 0.0266
|
-0.034 Liters
Standard Error 0.0278
|
Adverse Events
UMEC/VI 62.5/25 mcg
Placebo
Serious adverse events
| Measure |
UMEC/VI 62.5/25 mcg
n=198 participants at risk
Participants received umeclidinium (UMEC)/ vilanterol trifenatate (VI) 62.5 mcg/25 mcg each morning (once daily) as one inhalation via the Dry Powder Inhaler (DPI) in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed (prn)' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
Placebo
n=198 participants at risk
Participants received placebo each morning (once daily) as one inhalation via the DPI in one of the 2 treatment periods of 12 weeks. The treatment periods were separated by a washout period of 12-17 days; all par. were provided with albuterol for use on an 'as needed' basis throughout the run-in, washout and study treatment periods while on investigational product.
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
1.5%
3/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Infections and infestations
Pneumonia
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Infections and infestations
Cellulitis
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Infections and infestations
Gastroenteritis
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Cardiac disorders
Atrial thrombosis
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Cardiac disorders
Cardiac failure congestive
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Immune system disorders
Anaphylactic shock
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
|
Vascular disorders
Leriche syndrome
|
0.00%
0/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
0.51%
1/198 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of investigational product and until one day after last dose (approximately Week 25).
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population.
|
Other adverse events
Adverse event data not reported
Additional Information
GSK Response Center
GlaxoSmithKline
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