Clinical Trial Results:
A randomised, double-blind, double-dummy, parallel group study to evaluate the efficacy and safety of flutica one furoate /vil nterol trifenatate (FF/VI) inhalation powder delivered once daily compared to fluticasone propionate delivered twice daily in the treatment of asthma in adolescent and adult subjects of Asian ancestry currently treated with high-strength inhaled corticosteroids or mid-strength IC S/LABA combination therapy.
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Summary
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EudraCT number |
2015-004868-11 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
01 Feb 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
20 Jan 2017
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First version publication date |
20 Jan 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 |
113714
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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 |
09 Apr 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 |
01 Feb 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 |
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Actual start date of recruitment |
17 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: 200
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Country: Number of subjects enrolled |
Korea, Republic of: 59
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Country: Number of subjects enrolled |
Philippines: 50
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Worldwide total number of subjects |
309
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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) |
4
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Adults (18-64 years) |
276
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From 65 to 84 years |
29
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 313 participants were randomized to treatment. However, 4 participants were randomized in error and did not receive any study treatment; thus, these participants were not included in the Intent-to-Treat (ITT) Population, 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 meet 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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Fluticasone furoate/vilanterol 200/25 µg once daily | ||||||||||||||||||||||||||||||
Arm description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 200/25 micrograms (µg) once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fluticasone Furoate/Vilanterol (FF/VI) Trifenatate (200/25 mcg)
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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 |
Administered once daily in the evening by using a Novel Dry Powder Inhaler (NDPI)
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Arm title
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Fluticasone propionate 500 µg twice daily (BID) | ||||||||||||||||||||||||||||||
Arm description |
Participants received fluticasone propionate (FP) 500 µg inhalation powder BID (in the morning and evening), via the DISKUS, for a period of 12 weeks. | ||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||
Investigational medicinal product name |
Fluticasone propionate (500 mcg)
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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 |
administered twice daily via DISKUS Inhaler
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Baseline characteristics reporting groups
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Reporting group title |
Fluticasone furoate/vilanterol 200/25 µg once daily
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Reporting group description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 200/25 micrograms (µg) once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone propionate 500 µg twice daily (BID)
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Reporting group description |
Participants received fluticasone propionate (FP) 500 µg inhalation powder BID (in the morning and evening), via the DISKUS, for a period of 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fluticasone furoate/vilanterol 200/25 µg once daily
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Reporting group description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 200/25 micrograms (µg) once daily (OD) in the evening,via a Dry Powder Inhaler (DPI), for a period of 12 weeks. | ||
Reporting group title |
Fluticasone propionate 500 µg twice daily (BID)
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Reporting group description |
Participants received fluticasone propionate (FP) 500 µg inhalation powder BID (in the morning and evening), via the DISKUS, 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. Intent-to-Treat (ITT) Population: all participants randomized to treatment who received >=1 dose of trial medication. The primary endpoint analysis only included participants who had PM PEF data for >=4 days in the BL week prior to randomization and >=4 days after randomization. Only participants available at the indicated time point were assessed.
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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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| Notes [1] - Intent-to-Treat (ITT) Population [2] - Intent-to-Treat (ITT) Population |
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Statistical analysis title |
Statistical analysis 1 | ||||||||||||
Comparison groups |
Fluticasone propionate 500 µg twice daily (BID) v Fluticasone furoate/vilanterol 200/25 µg once daily
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Number of subjects included in analysis |
306
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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 |
28.5
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Confidence interval |
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95% | ||||||||||||
sides |
2-sided
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lower limit |
20.1 | ||||||||||||
upper limit |
36.9 | ||||||||||||
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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. Analysis was performed using ANCOVA with covariates of Baseline, region, sex, age, and treatment. ITT Population. In addition, the analysis only included participants who had PM PEF data for at least 2 days in the Baseline week prior to randomization and at least 2 days after randomization. Only those participants available at the indicated time point were assessed.
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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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| Notes [3] - ITT Population [4] - ITT Population |
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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 |
Number of inhalations of rescue albuterol/salbutamol inhalation aerosol used during the day and night was recorded by the participants (Par.) in a daily diary. A 24-hour period in which a par. responses to both the morning and evening assessments indicated no use of rescue medication was considered as rescue free. Par. ( who were rescue free for 24-hour periods during the 12-week Treatment Period were assessed. Baseline value was derived from the last 7 days of the daily diary prior to the randomization (ran.) of the par. 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. ITT Population.In addition, analysis only included par. who had rescue-free 24-hour period data for at least 2 days in the Baseline week prior to ran. and at least 2 days after ran. Only those par. available at the indicated time point were assessed.
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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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| Notes [5] - ITT Population [6] - ITT Population |
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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 dairy by the participants (Par) 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 par. 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 par.. Par. 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. ITT Population. In addition, the analysis only included par. who had symptom-free 24-hour period data for at least 2 days in the Baseline week prior to randomization and at least 2 days after randomization. Only those par. assessed.
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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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| Notes [7] - ITT Population [8] - ITT Population |
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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. ITT Population. Only those participants available at the indicated time point were assessed.
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End point type |
Secondary
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End point timeframe |
Baseline and Week 12
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| Notes [9] - ITT Population. Only those participants available at the indicated time point were assessed. [10] - ITT Population. Only those participants available at the indicated time point were assessed. |
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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 end of treatment (up to Study Day 84).
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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 |
15.1
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Reporting groups
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Reporting group title |
Fluticasone propionate 500 µg twice daily (BID)
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Reporting group description |
Participants received fluticasone propionate (FP) 500 µg inhalation powder BID (in the morning and evening), via the DISKUS, for a period of 12 weeks. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Fluticasone furoate/vilanterol 200/25 µg once daily
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Reporting group description |
Participants received fluticasone furoate (FF)/vilanterol (VI) 200/25 micrograms (µg) once daily (OD) in the evening, via a Dry Powder Inhaler (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 | |||
