Clinical Trial Results:
A Phase IV, 12-week, randomised, double-blind, triple dummy study to compare single inhaler triple therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) with multiple inhaler therapy (budesonide/formoterol plus tiotropium) based on lung function and symptoms in participants with chronic obstructive pulmonary disease
Summary
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EudraCT number |
2017-001149-28 |
Trial protocol |
DE CZ NL |
Global end of trial date |
14 Mar 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
01 Feb 2020
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First version publication date |
01 Feb 2020
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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 |
207608
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
GlaxoSmithKline
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Sponsor organisation address |
980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS
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Public contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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Scientific contact |
GSK Response Center, GlaxoSmithKline, 1 8664357343, GSKClinicalSupportHD@gsk.com
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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 |
31 May 2019
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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 |
14 Mar 2019
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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 |
To evaluate the effects of single inhaler triple therapy (FF/UMEC/VI) compared to multiple inhaler triple combination therapy with budesonide/formoterol plus tiotropium after 12 weeks of treatment on lung function
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Protection of trial subjects |
Not applicable
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
25 Jun 2018
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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 |
Germany: 71
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Country: Number of subjects enrolled |
Czech Republic: 85
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Country: Number of subjects enrolled |
Netherlands: 24
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Country: Number of subjects enrolled |
United States: 548
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Worldwide total number of subjects |
728
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EEA total number of subjects |
180
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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) |
330
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From 65 to 84 years |
397
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85 years and over |
1
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Recruitment
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Recruitment details |
This was a randomized, multicenter, parallel group study where participants with chronic obstructive pulmonary disease (COPD) were randomized to receive either fluticasone furoate/umeclidinium/vilanterol or budesonide/formoterol plus tiotropium in a 1:1 ratio. The study was conducted across 65 centers in 4 countries. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
A total of 1036 participants were screened in the study, of which 215 failed during screening. Of the 821 participants who entered the run-in period, 92 were run-in failures. A total of 729 participants were randomized in the study, of which one participant was randomized in error. A total of 728 participants received randomized treatment. | ||||||||||||||||||||||||
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 |
Investigator, Monitor, Carer, Data analyst, Subject, Assessor | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg | ||||||||||||||||||||||||
Arm description |
Participants received fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 microgram (mcg) via the ELLIPTA (once daily in the morning) plus placebo to match budesonide/formoterol (BUD/FOR) via metered dose inhaler (MDI) (two inhalations twice daily) plus placebo to match tiotropium (TIO) via HandiHaler (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Fluticasone furoate/Umeclidinium/Vilanterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Fluticasone furoate/Umeclidinium/Vilanterol (100/62.5/25 mcg) was available as dry white powder to be administered via ELLIPTA once daily in the morning.
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Investigational medicinal product name |
Placebo matching Budesonide/Formoterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pressurised inhalation, suspension
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Routes of administration |
Inhalation use
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Dosage and administration details |
Participants received two inhalations of placebo matching Budesonide/Formoterol via MDI twice daily.
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Investigational medicinal product name |
Placebo matching Tiotropium
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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 |
Placebo matching tiotropium was available as hard gelatin capsule containing lactose. Participants received placebo matching tiotropium once daily in the morning via HandiHaler device.
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Investigational medicinal product name |
Albuterol/salbutamol
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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 short-acting Albuterol/Salbutamol as-rescue medication during the study period, if required.
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Arm title
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Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg | ||||||||||||||||||||||||
Arm description |
Participants received two inhalations of budesonide/formoterol 160/4.5 mcg via MDI in the morning and two inhalations in the evening (total dose of 320/9 mcg twice daily) plus tiotropium 18 mcg via HandiHaler (once daily in the morning) plus placebo to match fluticasone furoate/umeclidinium/vilanterol via the ELLIPTA (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Budesonide/Formoterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Pressurised inhalation, suspension
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Routes of administration |
Inhalation use
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Dosage and administration details |
Budesonide/Formoterol was available as suspension for inhalation. Participants received two inhalations of Budesonide/Formoterol (320/9 mcg) via MDI twice daily.
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Investigational medicinal product name |
Placebo matching Fluticasone furoate/Umeclidinium/Vilanterol
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Inhalation powder, pre-dispensed
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Routes of administration |
Inhalation use
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Dosage and administration details |
Placebo matching Fluticasone furoate/Umeclidinium/Vilanterol was available as dry white powder to be administered via ELLIPTA once daily in the morning.
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Investigational medicinal product name |
Tiotropium
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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 |
Tiotropium was available as a hard gelatin capsule containing 18 mcg of tiotropium bromide blended with lactose. Participants received tiotropium (18 mcg) once daily in the morning via HandiHaler device.
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Investigational medicinal product name |
Albuterol/salbutamol
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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 short-acting Albuterol/Salbutamol as-rescue medication during the study period, if required.
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Baseline characteristics reporting groups
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Reporting group title |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg
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Reporting group description |
Participants received fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 microgram (mcg) via the ELLIPTA (once daily in the morning) plus placebo to match budesonide/formoterol (BUD/FOR) via metered dose inhaler (MDI) (two inhalations twice daily) plus placebo to match tiotropium (TIO) via HandiHaler (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Reporting group description |
Participants received two inhalations of budesonide/formoterol 160/4.5 mcg via MDI in the morning and two inhalations in the evening (total dose of 320/9 mcg twice daily) plus tiotropium 18 mcg via HandiHaler (once daily in the morning) plus placebo to match fluticasone furoate/umeclidinium/vilanterol via the ELLIPTA (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg
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Reporting group description |
Participants received fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 microgram (mcg) via the ELLIPTA (once daily in the morning) plus placebo to match budesonide/formoterol (BUD/FOR) via metered dose inhaler (MDI) (two inhalations twice daily) plus placebo to match tiotropium (TIO) via HandiHaler (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||
Reporting group title |
Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Reporting group description |
Participants received two inhalations of budesonide/formoterol 160/4.5 mcg via MDI in the morning and two inhalations in the evening (total dose of 320/9 mcg twice daily) plus tiotropium 18 mcg via HandiHaler (once daily in the morning) plus placebo to match fluticasone furoate/umeclidinium/vilanterol via the ELLIPTA (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. |
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End point title |
Weighted mean change from Baseline in forced expiratory volume in 1 second (FEV1) over 0-24 hours at Week 12 for modified per protocol (mPP) population | ||||||||||||
End point description |
FEV1 is the maximum amount of air that can be forced out in 1 second after taking a deep breath. Serial FEV1 assessments were performed at multiple time points (-30, -5 minutes[m] pre-dose and 5m, 15m, 30m, 1 hour[h], 3h, 6h, 12h, 15h, 21h, 23h and 24h post-dose) at Week 12. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. Baseline FEV1 is average of the two FEV1 measurements made at 30m and 5m pre-dose on Day 1. Weighted mean change from Baseline was calculated by subtracting post-dose weighted mean FEV1 from Baseline FEV1. mPP Population included participants in Intent-to-Treat (ITT) population who do not have protocol deviation of not meeting eligibility or randomization criteria. Only those participants with data available at the specified time points were analyzed.
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End point type |
Primary
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End point timeframe |
Baseline and Week 12
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Notes [1] - mPP Population [2] - mPP Population |
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
The primary treatment effect estimated (hypothetical effect) excluded data following intercurrent events: discontinuation of treatment, taking wrong treatment, taking prohibited medication, unblinding, noncompliance, COPD exacerbation or pneumonia.
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Number of subjects included in analysis |
554
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
Method |
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Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.015
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.013 | ||||||||||||
upper limit |
0.043 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.0143
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Notes [3] - Non-inferiority was to be demonstrated, if the lower bound of the two-sided 95 percentage (%) confidence interval around the (FF/UMEC/VI versus BUD/FOR+TIO) treatment difference was above -50 milliliter. |
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End point title |
Weighted mean change from Baseline in FEV1 over 0-24 hours at Week 12 for ITT population | ||||||||||||
End point description |
FEV1 is the maximum amount of air that can be forced out in 1 second after taking a deep breath. Serial FEV1 assessments were performed at multiple time points (-30 and -5m pre-dose, and 5m, 15m, 30m, 1h, 3h, 6h, 12h, 15h, 21h, 23h and 24h post dose) over 24h period at Week 12. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. Baseline FEV1 is the average of the two FEV1 measurements made at 30m and 5m pre-dose on Day 1. Weighted mean change from Baseline at week 12 was calculated by subtracting weighted mean FEV1 at week 12 from Baseline FEV1. ITT Population included all randomized participants, excluding those who were randomized in error. Only those participants with data available at the specified time points were analyzed.
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End point type |
Primary
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End point timeframe |
Baseline and Week 12
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Notes [4] - ITT Population [5] - ITT Population |
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
The treatment effect to be estimated was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis.
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Number of subjects included in analysis |
668
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
= 0.335 [6] | ||||||||||||
Method |
Mixed model repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.013
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.014 | ||||||||||||
upper limit |
0.04 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.0138
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Notes [6] - The analysis was performed using mixed model repeated measures analysis, which included covariates of Baseline FEV1, geographical region, treatment, visit, visit by treatment and visit by Baseline interaction. |
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End point title |
Change from Baseline in trough FEV1 on Day 2, Day 28, Day 84 and Day 85 | ||||||||||||||||||||||||
End point description |
FEV1 is an important measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 was measured using spirometry. For Day 2 and Day 85, trough FEV1 was defined as the mean of the 23-hour and 24-hour serial spirometry FEV1 measurements. For Day 28 and Day 84, trough FEV1 was defined as the average of the pre-dose FEV1 measurements recorded before the morning dose of randomized study treatment. Change from Baseline in trough FEV1 was calculated by subtracting post-dose trough FEV1 value from Baseline FEV1, where Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. The treatment effect to be estimated for trough FEV1 was hypothetical effect if all participants stayed on their randomized study treatment. Only those participants with data available at the specified time points were analyzed (represented by n= X in the category titles).
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End point type |
Secondary
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End point timeframe |
Baseline, Days 2, 28, 84 and 85
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Notes [7] - ITT Population [8] - ITT Population |
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Statistical analysis title |
Statistical Analysis 1 | ||||||||||||||||||||||||
Statistical analysis description |
Day 2
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Number of subjects included in analysis |
717
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.481 [9] | ||||||||||||||||||||||||
Method |
Mixed model repeated measures | ||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||
Point estimate |
-0.01
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-0.037 | ||||||||||||||||||||||||
upper limit |
0.018 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.0139
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Notes [9] - Only if superiority is achieved on the primary study endpoint, then inferences can be made on change from Baseline in trough FEV1 on Day 2 using p-values. |
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Statistical analysis title |
Statistical Analysis 2 | ||||||||||||||||||||||||
Statistical analysis description |
Day 28
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Number of subjects included in analysis |
717
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 [10] | ||||||||||||||||||||||||
Method |
Mixed model repeated measures | ||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||
Point estimate |
0.061
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.037 | ||||||||||||||||||||||||
upper limit |
0.086 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.0124
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Notes [10] - Only if superiority is achieved on the primary study endpoint, then inferences can be made on change from Baseline in trough FEV1 on Day 28 using p-values. |
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Statistical analysis title |
Statistical Analysis 3 | ||||||||||||||||||||||||
Statistical analysis description |
Day 84
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Number of subjects included in analysis |
717
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
< 0.001 [11] | ||||||||||||||||||||||||
Method |
Mixed model repeated measures | ||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||
Point estimate |
0.058
|
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Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.032 | ||||||||||||||||||||||||
upper limit |
0.084 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
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Dispersion value |
0.0133
|
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Notes [11] - Only if superiority is achieved on the primary study endpoint, then inferences can be made on change from Baseline in trough FEV1 on Day 84 using p-values. |
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Statistical analysis title |
Statistical Analysis 4 | ||||||||||||||||||||||||
Statistical analysis description |
Day 85
|
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
|
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Number of subjects included in analysis |
717
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
superiority | ||||||||||||||||||||||||
P-value |
= 0.007 [12] | ||||||||||||||||||||||||
Method |
Mixed model repeated measures | ||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||
Point estimate |
0.038
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
0.01 | ||||||||||||||||||||||||
upper limit |
0.066 | ||||||||||||||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||||||||||||||
Dispersion value |
0.014
|
||||||||||||||||||||||||
Notes [12] - Only if superiority is achieved on the primary study endpoint, then inferences can be made on change from Baseline in trough FEV1 on Day 85 using p-values. |
|
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End point title |
Weighted mean change from Baseline in FEV1 over 0-24 hours on Day 1 | ||||||||||||
End point description |
FEV1 is the maximum amount of air that can be forced out in 1 second after taking a deep breath. FEV1 was measured using spirometry. Serial FEV1 assessments were performed at multiple time points (-30 and -5 minutes pre-dose, and 5 minutes, 15 minutes, 30 minutes, 1 hour, 3 hours, 6 hours, 12 hours, 15 hours, 21 hours, 23 hours and 24 hours post dose) over 24-hour period on Day 1. The weighted mean was derived by calculating the area under the FEV1 time curve (AUC) over the actual time of assessment relative to the time of dosing using the trapezoidal rule, and then dividing the value by the time interval over which the AUC was calculated. Baseline FEV1 is the average of the two FEV1 measurements made at 30 minutes and 5 minutes pre-dose on Day 1. Weighted mean change from Baseline on Day 1 was calculated by subtracting weighted mean FEV1 on Day 1 from Baseline FEV1. Only those participants with data available at the specified time points were analyzed.
|
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End point type |
Secondary
|
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End point timeframe |
Baseline and Day 1
|
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|
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Notes [13] - ITT Population [14] - ITT Population |
|||||||||||||
Statistical analysis title |
Statistical Analysis 1 | ||||||||||||
Statistical analysis description |
The treatment effect to be estimated was hypothetical effect if all participants stayed on their randomized study treatment. Only on treatment data was included in analysis.
|
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Comparison groups |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg v Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
|
||||||||||||
Number of subjects included in analysis |
709
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
= 0.415 [15] | ||||||||||||
Method |
Mixed model repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.009
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.03 | ||||||||||||
upper limit |
0.013 | ||||||||||||
Variability estimate |
Standard error of the mean
|
||||||||||||
Dispersion value |
0.011
|
||||||||||||
Notes [15] - Only if superiority is achieved on the primary study endpoint, then inferences can be made on weighted mean change from Baseline in FEV1 over 0-24 hours on Day 1 using p-values. |
|
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Adverse events information
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Timeframe for reporting adverse events |
Serious adverse events (SAEs) and non-SAEs were reported from start of study treatment and up to Week 13
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Adverse event reporting additional description |
Non-SAEs and SAEs were reported for ITT Population. Adverse events were presented treatment-wise.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
22.0
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Reporting groups
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Reporting group title |
Fluticasone furoate/Umeclidinium/Vilanterol 100/62.5/25 mcg
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Reporting group description |
Participants received fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) 100/62.5/25 microgram (mcg) via the ELLIPTA (once daily in the morning) plus placebo to match budesonide/formoterol (BUD/FOR) via metered dose inhaler (MDI) (two inhalations twice daily) plus placebo to match tiotropium (TIO) via HandiHaler (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Budesonide/Formoterol 320/9 mcg plus Tiotropium 18 mcg
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Reporting group description |
Participants received two inhalations of budesonide/formoterol 160/4.5 mcg via MDI in the morning and two inhalations in the evening (total dose of 320/9 mcg twice daily) plus tiotropium 18 mcg via HandiHaler (once daily in the morning) plus placebo to match fluticasone furoate/umeclidinium/vilanterol via the ELLIPTA (once daily in the morning) for 84 days. Participants received albuterol/salbutamol as rescue medication during conduct of the study, if required. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 3% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
|||
Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
17 Jul 2018 |
This amendment was required to update the QT interval corrected for heart rate (QTc) stopping criteria to that which was used in the Phase III Trelegy registration studies. In addition, a section describing Smoking Cessation Counselling has been added as does a corresponding assessment at the end of study (Visit 4). Clarified that it is preferable to have the participants stay at the clinic or approved facility during the serial spirometry assessments. The physical form of Symbicort and matching placebo was reported as a solution for inhalation, which is incorrect, and should be corrected to a suspension for inhalation. An additional footnote has been added to the Schedule of Activities (SoA), to provide clarity on the collection of trough forced expiratory volume in 1 second (FEV1) spirometry on Day 28. Clarified that run-in treatment will be collected at Visit 2. Correction made (reference section) regarding prohibited medications within a specified time interval during pre-screening and prior to Visit 1. Also, wording regarding suggested order for assessments and procedures had been added to the end of the Schedule of Activities section. Removed reference to Fridericia formula in calculation of QTc. Clarification regarding collecting the Chronic Obstructive Pulmonary Disease (COPD) Assessment Test (CAT) assessment questionnaire prior to the Saint George’s Respiratory Questionnaire for COPD participants (SGRQ-C) had also been provided along with clarification that vital signs should be collected before the electrocardiogram (ECG) and prior to spirometry. Corrected reporting time regarding pregnancy. Routine urinalysis assessment has been deleted as this will not be collected during the study. Finally, added wording to Genetics Appendix regarding withdraw process and sample destruction process. |
||
Interruptions (globally) |
|||
Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |