Trial Outcomes & Findings for A Study to Evaluate the Effect of Umeclidinium (UMEC) as Combination Therapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD) (NCT NCT02257372)
NCT ID: NCT02257372
Last Updated: 2017-08-17
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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 was measured using spirometry. BL FEV1 is the mean of the two assessments made 30 and 5 minutes (min) pre-dose on Day 1.Change from BL was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis was performed using mixed model repeated measures with covariates of treatment, BL FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA, smoking status, Day, Day by BL interaction and Day by treatment interaction, where Day is nominal.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
236 participants
Primary outcome timeframe
Baseline (BL) and Day 85
Results posted on
2017-08-17
Participant Flow
Participants had used one of the following inhaled corticosteroids (ICS)/long-acting beta2-agonist (LABA) combinations for at least 30 days prior to Screening: Fluticasone Propionate/Salmeterol (FSC) 500/50 microgram (mcg) twice-daily (bid); budesonide/formoterol 200/6 mcg bid or 400/12 mcg bid; ICS/LABA combinations per study procedures manual.
Participants who met eligibility criteria at screening completed an approximately one week run-in period and participants who met the randomisation criteria were entered a 12-week treatment period. A total of 266 participants with chronic obstructive pulmonary disease (COPD) were screened; 236 participants randomized and entered into the study.
Participant milestones
| Measure |
Placebo+ICS/LABA
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
|
Umeclidinium 62.5 mcg+ICS/LABA
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
|
|---|---|---|
|
Overall Study
STARTED
|
117
|
119
|
|
Overall Study
COMPLETED
|
110
|
109
|
|
Overall Study
NOT COMPLETED
|
7
|
10
|
Reasons for withdrawal
| Measure |
Placebo+ICS/LABA
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
|
Umeclidinium 62.5 mcg+ICS/LABA
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
|
|---|---|---|
|
Overall Study
Adverse Event
|
3
|
7
|
|
Overall Study
Lack of Efficacy
|
2
|
1
|
|
Overall Study
Protocol Violation
|
1
|
1
|
|
Overall Study
Lost to Follow-up
|
0
|
1
|
|
Overall Study
Withdrew consent
|
1
|
0
|
Baseline Characteristics
A Study to Evaluate the Effect of Umeclidinium (UMEC) as Combination Therapy in Subjects With Chronic Obstructive Pulmonary Disease (COPD)
Baseline characteristics by cohort
| Measure |
Placebo+ICS/LABA
n=117 Participants
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
|
Umeclidinium 62.5 mcg+ICS/LABA
n=119 Participants
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
|
Total
n=236 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
63.1 Years
STANDARD_DEVIATION 7.86 • n=93 Participants
|
65.2 Years
STANDARD_DEVIATION 7.46 • n=4 Participants
|
64.1 Years
STANDARD_DEVIATION 7.72 • n=27 Participants
|
|
Sex: Female, Male
Female
|
42 Participants
n=93 Participants
|
36 Participants
n=4 Participants
|
78 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
75 Participants
n=93 Participants
|
83 Participants
n=4 Participants
|
158 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
Asian - Central/South Asian Heritage
|
1 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
1 Participants
n=27 Participants
|
|
Race/Ethnicity, Customized
White - White/Caucasian/European
|
116 Participants
n=93 Participants
|
119 Participants
n=4 Participants
|
235 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline (BL) and Day 85Population: Intent-to-treat (ITT) population: all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period. Only participants with data available at specific timepoint were analyzed.
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 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after dosing on Day 84 (Week 12). Trough FEV1 was measured using spirometry. BL FEV1 is the mean of the two assessments made 30 and 5 minutes (min) pre-dose on Day 1.Change from BL was calculated as the trough FEV1 value on Day 85 minus the BL value. Analysis was performed using mixed model repeated measures with covariates of treatment, BL FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA, smoking status, Day, Day by BL interaction and Day by treatment interaction, where Day is nominal.
Outcome measures
| Measure |
Placebo+ICS/LABA
n=110 Participants
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
|
Umeclidinium 62.5 mcg+ICS/LABA
n=109 Participants
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed
|
|---|---|---|
|
Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) on Day 85
|
-0.033 Liter
Standard Error 0.0184
|
0.090 Liter
Standard Error 0.0183
|
SECONDARY outcome
Timeframe: Baseline and Day 84Population: 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 weighted mean FEV1 was derived by calculating the area under the curve, and then dividing the value by the relevant time interval. The weighted mean was calculated by performing six-hour serial spirometry from the pre-dose FEV1 and post-dose FEV1 measurements at 15 minutes, 30 minutes, 1 hour, 3 hours and 6 hours. Baseline FEV1 is the mean of the two assessments made 30 and 5 min pre-dose on Treatment Day 1. Change from Baseline was calculated as weighted mean value on Day 84 minus the Baseline value. Analysis was performed using mixed model repeated measures with covariates of treatment, baseline FEV1 (mean of the values measured at 30 min and 5 min pre-dose on Day 1), type of ICS/LABA , smoking status, Day, Day by baseline interaction and Day by treatment interaction, where Day is nominal.
Outcome measures
| Measure |
Placebo+ICS/LABA
n=110 Participants
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed.
|
Umeclidinium 62.5 mcg+ICS/LABA
n=107 Participants
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed
|
|---|---|---|
|
Change From Baseline in Weighted Mean 0-6 Hour FEV1 Obtained Post-dose on Day 84
|
0.035 Liter
Standard Error 0.0175
|
0.184 Liter
Standard Error 0.0176
|
Adverse Events
Placebo+ICS/LABA
Serious events: 5 serious events
Other events: 35 other events
Deaths: 0 deaths
Umeclidinium 62.5 mcg+ICS/LABA
Serious events: 6 serious events
Other events: 25 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo+ICS/LABA
n=117 participants at risk
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed
|
Umeclidinium 62.5 mcg+ICS/LABA
n=119 participants at risk
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
|
|---|---|---|
|
Infections and infestations
Empyema
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.84%
1/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Vascular disorders
Aortic aneurysm rupture
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.84%
1/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.00%
0/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
2.6%
3/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
2.5%
3/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Nervous system disorders
Motor neuron disease
|
0.85%
1/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.00%
0/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.84%
1/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.84%
1/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Infections and infestations
Pseudomembranous colitis
|
0.00%
0/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
0.84%
1/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
Other adverse events
| Measure |
Placebo+ICS/LABA
n=117 participants at risk
Participants received double-blind placebo via a dry powder inhaler (DPI) once daily and an open-label inhaled corticosteriod (ICS)/Long-acting beta2-agonist(LABA) administered according to the label instructions for 12 weeks. Participants also received albuterol/salbutamol via a metered-dose-inhaler (MDI) or nebules as rescue medication throughout the study for use as needed
|
Umeclidinium 62.5 mcg+ICS/LABA
n=119 participants at risk
Participants received Umeclidinium 62.5 microgram(mcg) via a DPI once daily and an open-label ICS/LABA administered according to label instructions for 12 weeks. Participants also received albuterol/salbutamol via a MDI or nebules as rescue medication throughout the study for use as needed.
|
|---|---|---|
|
Infections and infestations
Nasopharyngitis
|
14.5%
17/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
13.4%
16/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Nervous system disorders
Headache
|
6.8%
8/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
3.4%
4/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.3%
5/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
2.5%
3/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
4.3%
5/117 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in the treatment period.
|
1.7%
2/119 • On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study treatment and until the follow up contact (13 weeks).
On-treatment SAEs and non-serious AEs were reported for the ITT Population comprised all subjects randomized to treatment who received at least one dose of randomized study medication in 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.
- Publication restrictions are in place
Restriction type: OTHER