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A Phase IIIb Study to Evaluate the Efficacy of Umeclidinium/Vilanterol (UMEC/VI) in Subjects With Chronic Obstructive Pulmonary Disease (COPD)

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ClinicalTrials.gov Identifier: NCT02152605
Recruitment Status : Completed
First Posted : June 2, 2014
Results First Posted : February 25, 2016
Last Update Posted : November 9, 2017
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Pulmonary Disease, Chronic Obstructive
Interventions Drug: UMEC/VI
Drug: Placebo
Enrollment 498
Recruitment Details In this randomized, double-blind, placebo-controlled parallel study, eligible participants received Umeclidinium/Vilanterol(UMEC/VI) 62.5/25 microgram(mcg) once daily(via Dry Powder Inhaler[DPI]) or matching placebo(1:1) for 12 weeks.The study consisted of Run-in Period(7-14 days), treatment period(12 weeks) and follow up period(7+-2 days).
Pre-assignment Details A total of 627 participants who met eligibility criteria were screened; 498 participants were randomized and 496 comprised the Intent to Treat population.
Arm/Group Title Placebo UMEC/VI 62.5/25 mcg
Hide Arm/Group Description Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication. Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Period Title: Overall Study
Started 248 248
Completed 229 230
Not Completed 19 18
Reason Not Completed
Adverse Event             6             8
Lack of Efficacy             7             4
Protocol deviation             1             4
Lost to Follow-up             1             0
Withdrew consent             4             2
Arm/Group Title Placebo UMEC/VI 62.5/25 mcg Total
Hide Arm/Group Description Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication. Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication. Total of all reporting groups
Overall Number of Baseline Participants 248 248 496
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 248 participants 248 participants 496 participants
62.6  (8.23) 64.1  (8.70) 63.4  (8.49)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 248 participants 248 participants 496 participants
Female
99
  39.9%
104
  41.9%
203
  40.9%
Male
149
  60.1%
144
  58.1%
293
  59.1%
Race/Ethnicity, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 248 participants 248 participants 496 participants
African American/African Heritage 3 4 7
White - White/Caucasian/European 245 244 489
1.Primary Outcome
Title Change From Baseline in Mean St.George’s Respiratory Questionnaire (SGRQ) Total Score at Day 84
Hide Description The SGRQ is a disease-specific questionnaire, self-completed by participants(par), used to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). The SGRQ contains 76 items grouped into three domains (symptoms, activity and impacts). Analysis was performed using mixed model repeated measures with covariates of Baseline (scores recorded prior to dosing on Day 1) SGRQ total score, centre group, smoking status, Day, treatment(trt), Day by Baseline interaction and Day by trt interaction, where Day is nominal. Change from Baseline at a particular visit was calculated as the SGRQ total score at that visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life.
Time Frame Baseline and Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo UMEC/VI 62.5/25 mcg
Hide Arm/Group Description:
Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Overall Number of Participants Analyzed 210 212
Least Squares Mean (Standard Error)
Unit of Measure: Score on scale
-2.12  (0.808) -6.15  (0.803)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -4.03
Confidence Interval (2-Sided) 95%
-6.28 to -1.79
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Change From Baseline in Trough Forced Expiratory Volume in One Second (FEV1) at Day 84
Hide Description 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 28, 56 and 84. Baseline is defined as the assessment taken pre-dose on Treatment Day 1. Trough FEV1 is defined as the FEV1 value obtained 24 hours after the previous morning's dosing. Change from Baseline at a particular visit was calculated as the trough FEV1 at that visit minus 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.
Time Frame Baseline and Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Placebo UMEC/VI 62.5/25 mcg
Hide Arm/Group Description:
Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Overall Number of Participants Analyzed 224 227
Least Squares Mean (Standard Error)
Unit of Measure: Liter
0.030  (0.0183) 0.152  (0.0181)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 62.5/25 mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value 0.122
Confidence Interval (2-Sided) 95%
0.071 to 0.172
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline (BL) in Mean Number of Puffs of Rescue Medication Per Day Used Over Weeks 1-12
Hide Description Albuterol/salbutamol(A/S) was used as rescue medication and was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout treatment periods. The number of puffs of rescue medication (A/S) per day over the entire 12 week treatment period was recorded and analyzed. For rescue use, ‘day’ is referred as the period between one record of rescue use and the next. Total puffs of rescue for each day = number of salbutamol puffs + (2 x number of salbutamol nebules). Analysis performed using mixed model repeated measures with covariates of BL(mean number of total puffs over the duration from First Day; defined as Latest of [7 days before Visit 2 and day after Visit 1] to Last Day(defined as Day before Visit 2)), smoking status, centre group, four-week period, treatment and period by BL interaction. Change from BL used weeks 1-4, 5-8, and 9-12 as covariates in the model and the overall least squares mean change for weeks 1-12 is estimated.
Time Frame Week 1 amd Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-Treat (ITT) Population: all par. randomized to trt. who received at least one dose of randomized study drug. Par. represents all par. in the ITT population without missing covariate information and with at least one post BL measurement.
Arm/Group Title Placebo UMEC/VI 62.5/25mcg
Hide Arm/Group Description:
Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
Overall Number of Participants Analyzed 247 244
Least Squares Mean (Standard Error)
Unit of Measure: puffs per day
-0.6  (0.13) -1.4  (0.13)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, UMEC/VI 62.5/25mcg
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method Mixed Models Analysis
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean Difference
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-1.1 to -0.4
Estimation Comments [Not Specified]
Time Frame On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug untill follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]).
Adverse Event Reporting Description SAEs and non-serious AEs were collected in participants of the ITT population, comprised of all participants randomized to treatment who received at least one dose of randomized study medication in the treatment period.
 
Arm/Group Title Placebo UMEC/VI 62.5/25mcg
Hide Arm/Group Description Participants with chronic obstructive pulmonary disease (COPD) received matching placebo via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication. Participants with COPD received UMEC/VI 62.5/25mcg via DPI once daily for 12 weeks. In addition, albuterol/salbutamol was provided to participants to use on an as-needed basis for relief of COPD symptoms throughout the run-in and double-blind treatment periods. Participants were followed up 7 days after the last dose of study medication.
All-Cause Mortality
Placebo UMEC/VI 62.5/25mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Placebo UMEC/VI 62.5/25mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   13/248 (5.24%)   17/248 (6.85%) 
Cardiac disorders     
Myocardial ischaemia  1  0/248 (0.00%)  1/248 (0.40%) 
Cardiac arrest  1  0/248 (0.00%)  1/248 (0.40%) 
Atrial fibrillation  1  0/248 (0.00%)  1/248 (0.40%) 
Myocardial infarction  1  1/248 (0.40%)  1/248 (0.40%) 
Acute myocardial infarction  1  1/248 (0.40%)  1/248 (0.40%) 
Infections and infestations     
Pneumonia bacterial  1  1/248 (0.40%)  0/248 (0.00%) 
Appendicitis  1  0/248 (0.00%)  1/248 (0.40%) 
Pneumonia  1  2/248 (0.81%)  3/248 (1.21%) 
Injury, poisoning and procedural complications     
Joint injury  1  0/248 (0.00%)  1/248 (0.40%) 
Fall  1  0/248 (0.00%)  1/248 (0.40%) 
Metabolism and nutrition disorders     
Dyslipidaemia  1  0/248 (0.00%)  1/248 (0.40%) 
Musculoskeletal and connective tissue disorders     
Psoriatic arthropathy  1  0/248 (0.00%)  1/248 (0.40%) 
Arthralgia  1  1/248 (0.40%)  0/248 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Mediastinum neoplasm  1  0/248 (0.00%)  1/248 (0.40%) 
Nervous system disorders     
Transient ischaemic attack  1  0/248 (0.00%)  1/248 (0.40%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia  1  0/248 (0.00%)  1/248 (0.40%) 
Respiratory, thoracic and mediastinal disorders     
Chronic obstructive pulmonary disease  1  7/248 (2.82%)  8/248 (3.23%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 17.1
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Placebo UMEC/VI 62.5/25mcg
Affected / at Risk (%) Affected / at Risk (%)
Total   30/248 (12.10%)   28/248 (11.29%) 
Infections and infestations     
Nasopharyngitis  1  16/248 (6.45%)  13/248 (5.24%) 
Nervous system disorders     
Headache  1  16/248 (6.45%)  16/248 (6.45%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v 17.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02152605     History of Changes
Other Study ID Numbers: 201211
First Submitted: May 29, 2014
First Posted: June 2, 2014
Results First Submitted: October 19, 2015
Results First Posted: February 25, 2016
Last Update Posted: November 9, 2017