Clinical Trial Results:
12-week study with GW685698/GW642444 in Asthma (low dose) Centralised D2014-0774
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Summary
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EudraCT number |
2015-004871-59 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
16 Jul 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
12 Feb 2017
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First version publication date |
12 Feb 2017
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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 |
113719
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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? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
22 Aug 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 |
16 Jul 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 |
TBD
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Jan 2012
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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 |
China: 360
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Country: Number of subjects enrolled |
Korea, Republic of: 124
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Country: Number of subjects enrolled |
Philippines: 78
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Worldwide total number of subjects |
562
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EEA total number of subjects |
0
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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) |
10
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Adults (18-64 years) |
497
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From 65 to 84 years |
54
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85 years and over |
1
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Recruitment
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Recruitment details |
A total of 311 participants were randomized to treatment. However, 4 participants were randomized in error and did not receive any study treatment. These participants were not included in the Intent-to-Treat (ITT) Population, which was comprised of all participants randomized to treatment who received >=1 dose of trial medication. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
At screening, participants who met all of the inclusion criteria entered a 2-week Run-in Period. Participants continued on inhaled corticosteroid (ICS) therapy throughout the Run-in Period. At the end of the Run-in Period, participants meeting the randomization criteria entered a 12-week Treatment Period and received one of the two treatments. | |||||||||||||||||||||||||||
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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 | |||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||||||||||||||||||||
Arm description |
Participants received placebo once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | |||||||||||||||||||||||||||
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 |
Participants received placebo once daily in the evening, via a novel dry powder inhaler, for a period of 12 weeks.
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Arm title
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Fluticasone furoate/vilanterol 100/25 µg once daily | |||||||||||||||||||||||||||
Arm description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 100/25 micrograms (µg) OD in the evening,via a DPI, for a period of 12 weeks. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Fluticasone Furoate (FF)/Vilanterol Trifenatate (VI) 100/25 µg
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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 |
Participants received FF/VI 100/25 µg once daily in the evening, via a novel dry powder inhaler, for a period of 12 weeks
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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 562 participants were screened for this study, 178 subjects were withdrawn at Screening Visit and additional 73 subjects were withdrawn during the run-in period. 311 participants were randomized to treatment; however, 4 participants were randomized in error and did not receive any study treatment. |
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone furoate/vilanterol 100/25 µg once daily
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Reporting group description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 100/25 micrograms (µg) OD in the evening,via a DPI, for a period of 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Participants received placebo once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | ||
Reporting group title |
Fluticasone furoate/vilanterol 100/25 µg once daily
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Reporting group description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 100/25 micrograms (µg) OD in the evening,via a DPI, for a period of 12 weeks. | ||
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End point title |
Mean change from Baseline (BL) in daily evening (PM) peak expiratory flow (PEF) averaged over the 12-week Treatment Period | ||||||||||||
End point description |
Peak Expiratory Flow is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily PM PEF over the 12-week Treatment Period minus the Baseline value. Analysis was performed using Analysis of Covariance (ANCOVA) with covariates of Baseline, region, sex, age, and treatment.
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End point type |
Primary
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End point timeframe |
Baseline and Weeks 1-12 (up to Day 84)
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
Fluticasone furoate/vilanterol 100/25 µg once daily v Placebo
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Number of subjects included in analysis |
304
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Analysis specification |
Pre-specified
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Analysis type |
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P-value |
< 0.001 | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Least Squares Mean Difference | ||||||||||||
Point estimate |
51
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
42.2 | ||||||||||||
upper limit |
59.7 | ||||||||||||
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End point title |
Mean change from Baseline in daily morning (AM) PEF averaged over the 12-week Treatment Period | ||||||||||||
End point description |
PEF is defined as the maximum airflow during a forced expiration beginning with the lungs fully inflated. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline was calculated as the value of the averaged daily AM PEF over the 12-week Treatment Period minus the Baseline value. A Repeated Measures analysis adjusted for Baseline, region, sex, age, treatment, week, week by Baseline interaction, and week by treatment interaction was used.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 1-12 (up to Day 84)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in the percentage of rescue-free 24- hour (hr) periods during the 12-week Treatment Period | ||||||||||||
End point description |
The number of inhalations of rescue albuterol/salbutamol inhalation aerosol (medication used to relieve symptoms immediately) used during the day and night was recorded by the participants in a daily diary. A 24-hour period in which a participant’s responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Participants who were rescue free for 24-hour periods during the 12-week Treatment Period were assessed. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 1-12 (up to Day 84)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean change from Baseline in the percentage of symptom-free 24- hour (hr) periods during the 12-week Treatment Period | ||||||||||||
End point description |
Asthma symptoms were recorded in a daily diary by the participants every day in the morning and evening before taking any rescue or study medication and before PEF measurement. A 24-hour period in which a participant’s responses to both the morning and evening assessments indicated no symptoms was considered as symptom free. The Baseline value was derived from the last 7 days of the daily diary prior to the randomization of the participant. Participants who were symptom free for 24-hour periods during the 12-week Treatment Period were assessed. Change from Baseline is calculated as the average value during the 12-week Treatment Period minus the value at Baseline. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Weeks 1-12 (up to Day 84)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Change from Baseline in total Asthma Quality of Life Questionnaire (AQLQ) score at Week 12 | ||||||||||||
End point description |
The AQLQ is a disease-specific, self-administered quality of life questionnaire developed to evaluate the impact of asthma treatments on the quality of life of asthma sufferers. The AQLQ contains 32 items in 4 domains: activity limitation (11 items), symptoms (12 items), emotional function (5 items), and environmental stimuli (4 items). The 32 items of the questionnaire are averaged to produce one overall quality of life score. The response format consists of a 7-point scale, where a value of 1 indicates “total impairment” and a value of 7 indicates “no impairment.” Change from Baseline was calculated as the Week 12 value minus the Baseline value. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| No statistical analyses for this end point | |||||||||||||
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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 (up to Study Day 91).
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Adverse event reporting additional description |
SAEs and non-serious AEs were reported for members of the Intent-to-Treat (ITT) Population, comprised of all participants randomized to treatment who received >=1 dose of trial medication.
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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 |
Placebo
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Reporting group description |
Participants received placebo OD in the evening,via a DPI, for a period of 12 weeks. | |||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone furoate/vilanterol 100/25 µg once daily
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Reporting group description |
Participants received FF/VI 100/25 µg OD in the evening,via a DPI, for a period of 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 | |||
