Clinical Trial Results:
A 12 week, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study to Evaluate the Efficacy of Umeclidinium/Vilanterol 62.5/25 mcg in Subjects with COPD
Summary
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EudraCT number |
2014-000529-19 |
Trial protocol |
HU DE RO BG |
Global end of trial date |
05 Mar 2015
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Results information
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Results version number |
v1(current) |
This version publication date |
04 Jun 2016
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First version publication date |
04 Jun 2016
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
201211
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom,
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Apr 2015
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Mar 2015
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to evaluate the effect of once-daily UMEC/VI 62.5/25mcg on health-related quality of life as measured using SGRQ total score compared to once-daily placebo in subjects with COPD.
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Protection of trial subjects |
To protect trial subjects, subjects were provided with supplemental salbutamol as rescue medication and the concurrent use of inhaled corticosteroids was allowed as maintenance treatment for COPD.
Subjects enrolled in the study had stable disease with no hospitalization for COPD within at least 12 weeks of screening and no use of systemic corticosteroids or antibiotics for a lower respiratory tract infection for at least 6 weeks prior to screening.
Subjects performed an ECG at screening to rule out significant cardiovascular abnormalities, and had a physical examination at the beginning and end of the study to assess health status.
Frequent assessment of adverse events and COPD exacerbations was obtained during the study at clinical visits conducted 1 day following the first dose of study medication and every 4 weeks thereafter to ensure patients safety was closely monitored.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Sep 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Bulgaria: 78
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Country: Number of subjects enrolled |
Germany: 67
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Country: Number of subjects enrolled |
Hungary: 97
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Country: Number of subjects enrolled |
Romania: 69
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Country: Number of subjects enrolled |
Ukraine: 66
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Country: Number of subjects enrolled |
United States: 159
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Country: Number of subjects enrolled |
Russian Federation: 91
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Worldwide total number of subjects |
627
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EEA total number of subjects |
311
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
336
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From 65 to 84 years |
289
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85 years and over |
2
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Recruitment
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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
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Screening details |
A total of 627 participants who met eligibility criteria were screened; 498 participants were randomized and 496 comprised the Intent to Treat (ITT) population. | ||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
12-Week Treatment Period (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||
Arm 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. | ||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Dry white powder delivered via DPI (2 strips with 30 blisters each, first containing lactose + magnesium stearate per blister and the second containing lactose per blister), administered as one inhalation of placebo, once daily in the morning
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Arm title
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UMEC/VI 62.5/25 mcg | ||||||||||||||||||||||||||||||
Arm description |
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. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Umeclidinium/Vilanterol (UMEC/VI)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder
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Routes of administration |
Inhalation use
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Dosage and administration details |
Dry white powder delivered via dray powder inhaler (DPI; 2 strips with 30 blisters each, first containing UMEC 62.5 mcg + lactose per blister and second containing VI 25 mcg + lactose + magnesium stearate per blister), administered as one inhalation of UMEC/VI 62.5/25 mcg, once daily in the morning
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: A total of 627 participants who met eligibility criteria were screened; 498 participants were randomized and 496 comprised the Intent to Treat population. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
UMEC/VI 62.5/25 mcg
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting 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. | ||
Reporting group title |
UMEC/VI 62.5/25 mcg
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Reporting group description |
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. |
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End point title |
Change from Baseline in Mean St.George’s Respiratory Questionnaire (SGRQ) total score at Day 84 | ||||||||||||
End point description |
The SGRQ is a disease-specific questionnaire, self-completed by participants(par), to evaluate the effect of UMEC/VI on health-related quality of life as compared to placebo in par with COPD. The SGRQ contains 76 items grouped into three domains (symptoms, activity, impacts) and scores range from 0 (minimum, best possible health status) to 100 (maximum, worst possible health status). 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 was calculated as the SGRQ total score at a particular visit minus Baseline. Change from Baseline in total score of -4 units or lower is considered as clinically meaningful improvement in quality of life. Intent-to-Treat (ITT) Population included par who received at least one dose of randomized study drug.
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End point type |
Primary
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End point timeframe |
Baseline and Day 84
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Participants 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.
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Comparison groups |
UMEC/VI 62.5/25 mcg v Placebo
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Number of subjects included in analysis |
422
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least Squares Mean Difference | ||||||||||||
Point estimate |
-4.03
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-6.28 | ||||||||||||
upper limit |
-1.79 |
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End point title |
Change from Baseline in trough forced expiratory volume in one second (FEV1) at Day 84 | ||||||||||||
End point 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. Intent-to-Treat (ITT) Population included par 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 analysis
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End point type |
Secondary
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End point timeframe |
Baseline and Day 84
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Comparison groups |
UMEC/VI 62.5/25 mcg v Placebo
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Number of subjects included in analysis |
451
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least Squares Mean Difference | ||||||||||||
Point estimate |
0.122
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.071 | ||||||||||||
upper limit |
0.172 |
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End point title |
Change from Baseline (BL) in Mean number of puffs of rescue medication per day used over Weeks 1-12 | ||||||||||||
End point 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 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. ITT population was analyzed.
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End point type |
Secondary
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End point timeframe |
Week 1 to Week 12
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
Participants represent all participants in the ITT population without missing covariate information and with at least one post BL measurement.
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Comparison groups |
UMEC/VI 62.5/25 mcg v Placebo
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Number of subjects included in analysis |
491
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed models analysis | ||||||||||||
Parameter type |
Least Squares Mean Difference | ||||||||||||
Point estimate |
-0.7
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-1.1 | ||||||||||||
upper limit |
-0.4 |
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Adverse events information
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Timeframe for reporting adverse events |
On-treatment serious adverse events (SAEs) and non-serious adverse events (AEs) were collected from the start of study drug until follow-up (Follow-up is defined as up to Day 84 [-4 to +2 days]/Early withdrawal visit plus 7 days [± 2 days]).
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Adverse event reporting additional 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.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
UMEC/VI 62.5/25mcg
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Reporting group description |
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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting 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. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None |