Clinical Trial Results:
A randomized, multi-center, double-blind, doubledummy, parallel group study to evaluate the efficacy and safety of umeclidinium bromide/vilanterol compared with fluticasone propionate/salmeterol over 12 weeks in subjects with COPD
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Summary
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EudraCT number |
2012-000524-18 |
Trial protocol |
CZ ES HU DE DK NL |
Global end of trial date |
07 Oct 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
27 Apr 2016
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First version publication date |
01 May 2015
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Other versions |
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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 |
DB2116134
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01822899 | ||
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 |
26 Nov 2013
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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 |
07 Oct 2013
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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 |
Compare the efficacy and safety of UMEC/VI Inhalation Powder (62.5/25 μg once daily) with fluticasone propionate/salmeterol (500/50 μg twice-daily) over 12 weeks in subjects with COPD who have a history of infrequent COPD exacerbations
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Protection of trial subjects |
Several measures were taken to protect trials subjects: these included adverse event monitoring throughout the study, frequent clinic visits (approximately every 4 weeks) to monitor subject status, exclusion of patients with clinically significant and uncontrolled medical conditions and/or ECG findings, and use of treatment arms where all patients received pharmacologic treatment that was appropriate for the disease and disease severity under study.
Fluticasone propionate/salmeterol combination inhalation powder is a marketed product and was administered according to the local label. Fluticasone propionate/salmeterol has an acceptable safety profile for use. This conclusion is supported by the results of previously performed clinical studies and post-marketing experience (see local label).
All patients were on active treatment.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Apr 2013
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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 |
Netherlands: 62
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Country: Number of subjects enrolled |
Poland: 87
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Country: Number of subjects enrolled |
Spain: 60
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Country: Number of subjects enrolled |
Czech Republic: 87
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Country: Number of subjects enrolled |
Denmark: 42
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Country: Number of subjects enrolled |
Germany: 224
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Country: Number of subjects enrolled |
Hungary: 178
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Country: Number of subjects enrolled |
Russian Federation: 269
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Worldwide total number of subjects |
1009
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EEA total number of subjects |
740
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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) |
625
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From 65 to 84 years |
381
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85 years and over |
3
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Recruitment
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Recruitment details |
Participants who met the eligibility criteria at Screening (Visit 1) completed a 7- to 14-day Run-in Period, followed by a 12-week Treatment Period. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
A total of 717 participants, representing the enrolled participants, were randomized to study treatment. Of these, 716 participants comprised the Intent-to-Treat Population (participants randomized to treatment who received >=1 dose of randomized study medication in the treatment period). | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall Study (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, Monitor, Data analyst, Carer, Assessor | |||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Umeclidinium bromide/vilanterol 62.5/25 μg | |||||||||||||||||||||||||||
Arm description |
Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Umeclidinium bromide/vilanterol
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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 |
Respiratory use
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Dosage and administration details |
62.5/25 μg once-daily via dry powder inhaler
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Arm title
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Fluticasone propionate/salmeterol 500/50 μg | |||||||||||||||||||||||||||
Arm description |
Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
fluticasone propionate/salmeterol
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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 |
Respiratory use
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Dosage and administration details |
500/50 μg twice-daily via dry powder inhaler
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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: Although 1009 participants were enrolled in the trial, only 717 were randomized to treatment. Of these, 716 participants comprised the Intent-to-Treat Population (participants randomized to treatment who received >=1 dose of randomized study medication in the treatment period). |
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Baseline characteristics reporting groups
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Reporting group title |
Umeclidinium bromide/vilanterol 62.5/25 μg
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Reporting group description |
Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone propionate/salmeterol 500/50 μg
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Reporting group description |
Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Umeclidinium bromide/vilanterol 62.5/25 μg
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Reporting group description |
Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks. | ||
Reporting group title |
Fluticasone propionate/salmeterol 500/50 μg
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Reporting group description |
Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks. | ||
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End point title |
Change from Baseline (BL) in 0 to 24 hour weighted mean serial 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. The weighted mean was calculated from the pre-dose FEV1 and post-dose FEV1 measurements at 5 and 15 minutes and 1, 3, 6, 9, 12 (pre-evening dose), 13, 15, 18, 23, and 24 hours after the morning dose. Analysis was performed using an analysis of covariance (ANCOVA) model with covariates of treatment, Baseline FEV1 (mean of the two assessments made 30 minutes and 5 minutes pre-dose on Day 1), and smoking status.
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End point type |
Primary
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End point timeframe |
Baseline and Day 84
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| Notes [1] - Intent-to-Treat (ITT) Population [2] - Intent-to-Treat (ITT) Population |
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Statistical analysis title |
Analysis 1 | ||||||||||||
Comparison groups |
Umeclidinium bromide/vilanterol 62.5/25 μg v Fluticasone propionate/salmeterol 500/50 μg
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Number of subjects included in analysis |
669
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.08
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.046 | ||||||||||||
upper limit |
0.113 | ||||||||||||
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End point title |
Change from Baseline (BL) in trough forced expiratory volume in one second (FEV1) at Day 85 | ||||||||||||
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. BL is defined as the mean of the assessments made 30 and 5 min pre-dose on treatment (trt) Day 1. Trough FEV1 on Day 85 is defined as the mean of the FEV1 values obtained 23 and 24 hours after morning dosing on Day 84. Analysis was performed using a repeated measures model with covariates of trt, BL (mean of the 2 assessments made 30 and 5 min pre-dose on Day 1), smoking status, day, day by BL and day by trt interactions. The model used all available trough FEV1 values recorded on Days 28, 56, 84, and 85. Missing data were not directly imputed in this analysis; however, all non-missing data for a par. were used to estimate the trt effect for trough FEV1 at Day 85. Change from BL=value at Day 84 minus value at BL. Par. analyzed were those with data available at the time point; but, all par. without missing covariate information were included in the analysis.
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End point type |
Secondary
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End point timeframe |
Baseline and Day 85
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| Notes [3] - Intent-to-Treat (ITT) Population [4] - Intent-to-Treat (ITT) Population |
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Statistical analysis title |
Analysis 2 | ||||||||||||
Comparison groups |
Umeclidinium bromide/vilanterol 62.5/25 μg v Fluticasone propionate/salmeterol 500/50 μg
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Number of subjects included in analysis |
671
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Repeated measures | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.055 | ||||||||||||
upper limit |
0.125 | ||||||||||||
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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 medication until the follow-up contact (up to 13 weeks).
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Adverse event reporting additional description |
On-treatment 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 in the Treatment Period.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
16.0
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Reporting groups
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Reporting group title |
Umeclidinium bromide/vilanterol 62.5/25 μg
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Reporting group description |
Participants received umeclidinium bromide (UMEC) 62.5 micrograms (µg)/vilanterol (VI) 25 µg once daily (QD) each morning via a dry powder inhaler (DPI) and placebo twice daily (BID) (once in the morning and once in the evening) via a DPI for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone propionate/salmeterol 500/50 μg
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Reporting group description |
Participants received fluticasone propionate/salmeterol (FSC) 500 µg/50 µg BID (once in the morning and once in the evening) via a DPI and placebo administered QD via a DPI for 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 reported | |||
