Clinical Trial Results:
A 52-week, double-blind, randomized, multinational, multicentre, 2-arm parallel-group, active-controlled clinical trial of fixed combination of beclometasone dipropionate plus formoterol fumarate plus glycopyrrolate bromide administered via pMDI (CHF 5993) versus fixed combination of beclometasone dipropionate plus formoterol fumarate administered via pMDI in patients with chronic obstructive pulmonary disease
Summary
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EudraCT number |
2013-001057-27 |
Trial protocol |
GB BE HU DE IT CZ SK PL BG |
Global end of trial date |
14 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Feb 2017
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First version publication date |
10 Feb 2017
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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 |
CCD-1207-PR-0091
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01917331 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
TRILOGY: TRILOGY | ||
Sponsors
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Sponsor organisation name |
Chiesi Farmaceutici S.p.A.
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Sponsor organisation address |
Via Palermo 26/A, Parma, Italy, 43122
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Public contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., +39 0521 2791, ClinicalTrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A., +39 0521 2791, ClinicalTrials_info@chiesi.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 |
23 May 2016
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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 Jan 2016
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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 |
• Demonstrate superiority of CHF 5993 pMDI over CHF 1535 pMDI in terms of lung function (change from baseline in pre-dose and 2-hour post-dose morning FEV1 at Week 26).
• Demonstrate superiority of CHF 5993 pMDI over CHF 1535 pMDI in terms of dyspnea (Transition Dyspnea Index focal score at Week 26).
CHF 5993 = Fixed combination of BDP and FF and GB
CHF 1535=Fixed combination of BDP and FF
BDP = Beclomethasone dipropionate
COPD=Chronic obstructive pulmonary disease
FF=Formoterol fumarate
GB=Glycopyrronium bromide
pMDI=Pressurised metered dose inhaler
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Protection of trial subjects |
The study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practices (GCP) guidelines, and national legal requirements.
At all visits, from screening onward, concomitant medications, adverse events and vital signs were recorded, COPD exacerbations were assessed and 12-lead electrocardiogram (ECG) and physical examinations were performed. Treatment compliance was evaluated on the basis of the information recorded daily by the patient on the digital platform.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
21 Mar 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Argentina: 53
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Country: Number of subjects enrolled |
Mexico: 4
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Country: Number of subjects enrolled |
Romania: 105
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Country: Number of subjects enrolled |
Russian Federation: 320
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Country: Number of subjects enrolled |
Ukraine: 224
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Country: Number of subjects enrolled |
Poland: 113
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Country: Number of subjects enrolled |
Slovakia: 33
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Country: Number of subjects enrolled |
United Kingdom: 20
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Country: Number of subjects enrolled |
Belgium: 7
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Country: Number of subjects enrolled |
Bulgaria: 92
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Country: Number of subjects enrolled |
Czech Republic: 208
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Country: Number of subjects enrolled |
Germany: 63
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Country: Number of subjects enrolled |
Hungary: 103
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Country: Number of subjects enrolled |
Italy: 23
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Worldwide total number of subjects |
1368
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EEA total number of subjects |
767
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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) |
739
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From 65 to 84 years |
627
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85 years and over |
2
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Recruitment
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Recruitment details |
Overall, 1812 patients were screened according to inclusion and exclusion criteria; of these 1368 patients were randomized. | |||||||||||||||||||||||||||||||||
Pre-assignment
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Screening details |
Pre-screening visit was at most 1 week before the screening visit when inclusion/exclusion criteria were assessed and the run-in period of 2 weeks started. During the run-in period patients stopped their current treatment and received an open-label CHF 1535 pMDI to take as 2 puffs bid for 2 weeks (BDP 400 μg/FF 24 μg daily). | |||||||||||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall trial (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 | |||||||||||||||||||||||||||||||||
Blinding implementation details |
Interactive Response Technology was used to assign study medication kits in order to have an inventory control and patient dosing tracking. In addition, the IRT maintained quantities, kit numbers, drug types,batch/code number, expiration dates and it monitored inventory levels at all sites and managed the drug re-supply.
The canisters/actuators of CHF 5993 pMDI and CHF 1535 pMDI were of identical appearance.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Treatment A - fixed combination CHF 5993 100/6/12.5μg | |||||||||||||||||||||||||||||||||
Arm description |
Treatment A: CHF 5993 pMDI: Patients followed a schedule of 2 puffs of CHF 5993 100/6/12.5 μg bid. Therefore, the total daily dose was BDP/FF/GB 400/24/50 μg; BDP=Beclomethasone dipropionate GB=Glycopyrronium bromide FF=Formoterol fumarate CHF 5993 pMDI=Fixed combination of BDP 50μg, FF 6 μg, GB 12.5µg per metered dose | |||||||||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 5993 100/6/12.5 μg
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Investigational medicinal product code |
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Other name |
BDP/FF/GB, Fixed combination of beclomethasone dipropionate, formoterol fumarate, Glycopyrronium bromide
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Pharmaceutical forms |
Pressurised inhalation, solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Dose: BDP 100 μg, FF 6 μg, GB 12.5 μg per actuation, 2 puffs bid (twice daily).
Total daily dose: BDP 400 μg, FF 24 μg, GB 50 μg.
Mode of administration: pMDI using a standard actuator. If patients inhaled their usual COPD pMDI treatments with a spacer device, they were provided with the AeroChamber Plus™ to be used when taking the pMDI study treatments.
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Arm title
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Treatment B - fixed combination CHF 1535 100/6μg | |||||||||||||||||||||||||||||||||
Arm description |
Treatment B: CHF 1535 pMDI: Patients followed a schedule of 2 puffs of CHF 1535 100/6 μg bid. Therefore, the total daily dose was BDP/FF 400/24 μg. BDP=Beclomethasone dipropionate FF=Formoterol fumarate CHF 1535 pMDI=Fixed combination of BDP 100μg, FF 6 μg, | |||||||||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||||||||
Investigational medicinal product name |
CHF 1535 100/6 μg
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Investigational medicinal product code |
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Other name |
BDP/FF, Fixed combination of beclomethasone dipropionate and formoterol fumarate
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Pharmaceutical forms |
Pressurised inhalation, solution
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Routes of administration |
Inhalation use
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Dosage and administration details |
Dose: BDP 100 μg, FF 6 μg per actuation, 2 puffs bid. (twice daily).
Total daily dose: BDP 400 μg, FF 24 μg.
Mode of administration: pMDI using a standard actuator. If patients inhaled their usual COPD pMDI treatments with a spacer device, they were provided with the AeroChamber Plus™ to be used when taking the pMDI study treatments.
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Baseline characteristics reporting groups
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Reporting group title |
Treatment A - fixed combination CHF 5993 100/6/12.5μg
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Reporting group description |
Treatment A: CHF 5993 pMDI: Patients followed a schedule of 2 puffs of CHF 5993 100/6/12.5 μg bid. Therefore, the total daily dose was BDP/FF/GB 400/24/50 μg; BDP=Beclomethasone dipropionate GB=Glycopyrronium bromide FF=Formoterol fumarate CHF 5993 pMDI=Fixed combination of BDP 50μg, FF 6 μg, GB 12.5µg per metered dose | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment B - fixed combination CHF 1535 100/6μg
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Reporting group description |
Treatment B: CHF 1535 pMDI: Patients followed a schedule of 2 puffs of CHF 1535 100/6 μg bid. Therefore, the total daily dose was BDP/FF 400/24 μg. BDP=Beclomethasone dipropionate FF=Formoterol fumarate CHF 1535 pMDI=Fixed combination of BDP 100μg, FF 6 μg, | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Treatment A - fixed combination CHF 5993 100/6/12.5μg
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Reporting group description |
Treatment A: CHF 5993 pMDI: Patients followed a schedule of 2 puffs of CHF 5993 100/6/12.5 μg bid. Therefore, the total daily dose was BDP/FF/GB 400/24/50 μg; BDP=Beclomethasone dipropionate GB=Glycopyrronium bromide FF=Formoterol fumarate CHF 5993 pMDI=Fixed combination of BDP 50μg, FF 6 μg, GB 12.5µg per metered dose | ||
Reporting group title |
Treatment B - fixed combination CHF 1535 100/6μg
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Reporting group description |
Treatment B: CHF 1535 pMDI: Patients followed a schedule of 2 puffs of CHF 1535 100/6 μg bid. Therefore, the total daily dose was BDP/FF 400/24 μg. BDP=Beclomethasone dipropionate FF=Formoterol fumarate CHF 1535 pMDI=Fixed combination of BDP 100μg, FF 6 μg, |
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End point title |
1_Change from baseline in pre-dose morning FEV1 at week 26 | ||||||||||||
End point description |
FEV1=Forced expiratory volume in the 1st second. It is the volume of air that can be forced out in one second after taking a deep breath.
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End point type |
Primary
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End point timeframe |
Baseline to Week 26.
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Notes [1] - ITT population; Change from baseline available; [2] - ITT population; Change from baseline available; |
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Statistical analysis title |
Adjusted mean difference between treatment groups | ||||||||||||
Comparison groups |
Treatment B - fixed combination CHF 1535 100/6μg v Treatment A - fixed combination CHF 5993 100/6/12.5μg
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Number of subjects included in analysis |
1258
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Analysis specification |
Pre-specified
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Analysis type |
superiority [3] | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.081
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.052 | ||||||||||||
upper limit |
0.109 | ||||||||||||
Notes [3] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. Treatment A (CHF 5993 pMDI) - Treatment B (CHF 1535 pMDI) |
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End point title |
2_Change from baseline to 2-hour post-dose value of FEV1 at Week 26 | ||||||||||||
End point description |
Change from baseline to 2-hour post-dose value of FEV1 at Week 26.
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End point type |
Primary
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End point timeframe |
Baseline to 2-hour post-dose at Week 26.
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Notes [4] - ITT population; Change from baseline available; [5] - ITT population; Change from baseline available; |
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Statistical analysis title |
Adjusted mean difference between treatment groups | ||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
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Number of subjects included in analysis |
1240
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Analysis specification |
Pre-specified
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Analysis type |
superiority [6] | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.117
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.086 | ||||||||||||
upper limit |
0.147 | ||||||||||||
Notes [6] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, Country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. Treatment A (CHF 5993 pMDI) - Treatment B (CHF 1535 pMDI) |
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End point title |
3_TDI focal score at Week 26 | ||||||||||||
End point description |
TDI focal score is a symptom-based variable, used to assess breathlessness and the impact of intervention. The BDI/TDI is a clinical rating method based on a validated instrument, developed to measure the impact of dyspnoea on three domains: functional impairment, magnitude of task, and magnitude of effort.
The BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain with the TDI focal score consisting in the sum of each domain (i.e. from -9 to +9).
BDI and TDI are based on validated questionnaires. BDI focal score is the baseline value from which TDI focal score is assessed.
BDI=Baseline Dyspnoea Index
TDI=Transition Dyspnoea Index
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End point type |
Primary
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End point timeframe |
Baseline to Week 26.
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Notes [7] - ITT population; Change from baseline available; [8] - ITT population; Change from baseline available; |
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Statistical analysis title |
Adjusted mean difference between treatment groups | ||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
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Number of subjects included in analysis |
1261
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Analysis specification |
Pre-specified
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Analysis type |
superiority [9] | ||||||||||||
P-value |
= 0.16 | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.21
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
-0.08 | ||||||||||||
upper limit |
0.51 | ||||||||||||
Notes [9] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. Treatment A (CHF 5993 pMDI) - Treatment B (CHF 1535 pMDI) |
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End point title |
4_Change from baseline in pre-dose morning FEV1 at all study visits | |||||||||||||||||||||||||||
End point description |
Change from baseline in pre-dose morning FEV1 at all study visits.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
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End point type |
Secondary
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End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
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Notes [10] - ITT population (analysed) Wk 04 n=679 Wk 12 n=660 Wk 26 n=642 Wk 40 n=622 Wk 52 n=606 [11] - ITT population (analysed) Wk 04 n=669 Wk 12 n=654 Wk 26 n=616 Wk 40 n=597 Wk 52 n=578 |
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Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
The number of subjects in this analysis shown (1351) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects in this analysis with available data is 1348:
n (CHF 5993 pMDI)=679
n (CHF 1535 pMDI)=669
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Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
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Number of subjects included in analysis |
1351
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Analysis specification |
Pre-specified
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Analysis type |
superiority [12] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.071
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.047 | |||||||||||||||||||||||||||
upper limit |
0.094 | |||||||||||||||||||||||||||
Notes [12] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
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Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
The number of subjects in this analysis shown (1351) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects in this analysis with available data is 1314:
n (CHF 5993 pMDI)=660
n (CHF 1535 pMDI)=654
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Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
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Number of subjects included in analysis |
1351
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Analysis specification |
Pre-specified
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Analysis type |
superiority [13] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.068
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.042 | |||||||||||||||||||||||||||
upper limit |
0.094 | |||||||||||||||||||||||||||
Notes [13] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
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Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
The number of subjects in this analysis shown (1351) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects in this analysis with available data is 1258:
n (CHF 5993 pMDI)=642
n (CHF 1535 pMDI)=616
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Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
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Number of subjects included in analysis |
1351
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Analysis specification |
Pre-specified
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Analysis type |
superiority [14] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.081
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Confidence interval |
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level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
0.052 | |||||||||||||||||||||||||||
upper limit |
0.109 | |||||||||||||||||||||||||||
Notes [14] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
The number of subjects in this analysis shown (1351) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects in this analysis with available data is 1219:
n (CHF 5993 pMDI)=622
n (CHF 1535 pMDI)=597
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1351
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [15] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.077
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.046 | |||||||||||||||||||||||||||
upper limit |
0.108 | |||||||||||||||||||||||||||
Notes [15] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
The number of subjects in this analysis shown (1351) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects in this analysis with available data is 1184:
n (CHF 5993 pMDI)=606
n (CHF 1535 pMDI)=578
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1351
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [16] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.063
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.032 | |||||||||||||||||||||||||||
upper limit |
0.094 | |||||||||||||||||||||||||||
Notes [16] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
|
|||||||||||||
End point title |
5_Change from baseline to the average over the treatment period in pre-dose morning FEV1 | ||||||||||||
End point description |
Change from baseline to the average over the treatment period in pre-dose morning FEV1.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to the overall treatment period (Week 4 to Week 52).
|
||||||||||||
|
|||||||||||||
Notes [17] - ITT population; Change from baseline available; [18] - ITT population; Change from baseline available; |
|||||||||||||
Statistical analysis title |
Adjusted mean difference between treatment groups. | ||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups.
|
||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||
Number of subjects included in analysis |
1351
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [19] | ||||||||||||
P-value |
< 0.001 | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
0.072
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.048 | ||||||||||||
upper limit |
0.096 | ||||||||||||
Notes [19] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. CHF 5993 pMDI - CHF 1535 pMDI |
|
||||||||||||||||
End point title |
6_FEV1 response (change from baseline in pre-dose morning FEV1 ≥100 mL) at Week 26 and Week 52 | |||||||||||||||
End point description |
FEV1 response is defined as a change from baseline in pre-dose morning FEV1 ≥100 mL. If the change from baseline was <100 mL, the patient was classed as a non-responder in terms of FEV1. Subjects with missing pre-dose morning FEV1 value at the relevant time points were also classified as non-responders.
Results are shown as the number of responders for the comparison of CHF 5993 pMDI vs CHF 1535 pMDI.
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline to study visit at Week 26, Week 52.
|
|||||||||||||||
|
||||||||||||||||
Notes [20] - ITT population [21] - ITT population |
||||||||||||||||
Statistical analysis title |
Btw grp analysis, change in FEV1 ≥100 mL, Wk 26 | |||||||||||||||
Statistical analysis description |
Between group analysis (change from baseline in pre-dose morning FEV1 ≥100 mL, Week 26).
CHF 5993 pMDI / CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [22] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
2.299
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.817 | |||||||||||||||
upper limit |
2.91 | |||||||||||||||
Notes [22] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as factors and the baseline FEV1 value as a covariate. |
||||||||||||||||
Statistical analysis title |
Btw grp analysis, change in FEV1 ≥100 mL, Wk 52 | |||||||||||||||
Statistical analysis description |
Between group analysis (change from baseline in pre-dose morning FEV1 ≥100 mL, Week 52).
CHF 5993 pMDI / CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [23] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
2.061
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.621 | |||||||||||||||
upper limit |
2.62 | |||||||||||||||
Notes [23] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as factors and the baseline FEV1 value as a covariate. |
|
|||||||||||||||||||||||||||||||
End point title |
7_Change from baseline to 2-hour post-dose value of FEV1 at all study visits | ||||||||||||||||||||||||||||||
End point description |
Change from baseline to 2-hour post-dose value of FEV1 at all study visits.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline to 2-hour post-dose at each study visit (Week 0, 4, 12, 26, 40, 52).
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [24] - ITT population (analysed) W 0 n=683 W 4 n=675 W 12 n=657 W 26 n=631 W 40 n=615 W 52 n=598 [25] - ITT population (analysed) W 0 n=674 W 4 n=660 W 12 n=648 W 26 n=609 W 40 n=590 W 52 n=575 |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 0 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 0.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1357:
n (CHF 5993 p65) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [26] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.077
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.06 | ||||||||||||||||||||||||||||||
upper limit |
0.095 | ||||||||||||||||||||||||||||||
Notes [26] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1335:
n (CHF 5993 pMDI)=675
n (CHF 1535 pMDI)=660
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [27] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.116
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.09 | ||||||||||||||||||||||||||||||
upper limit |
0.141 | ||||||||||||||||||||||||||||||
Notes [27] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1305:
n (CHF 5993 pMDI)=657
n (CHF 1535 pMDI)=648
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [28] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.116
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.087 | ||||||||||||||||||||||||||||||
upper limit |
0.144 | ||||||||||||||||||||||||||||||
Notes [28] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1240:
n (CHF 5993 pMDI)=631
n (CHF 1535 pMDI)=609
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [29] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.117
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.086 | ||||||||||||||||||||||||||||||
upper limit |
0.147 | ||||||||||||||||||||||||||||||
Notes [29] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1205:
n (CHF 5993 pMDI)=615
n (CHF 1535 pMDI)=590
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [30] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.102
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.07 | ||||||||||||||||||||||||||||||
upper limit |
0.135 | ||||||||||||||||||||||||||||||
Notes [30] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments in 2-hour post-dose FEV1 at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1365) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1173:
n (CHF 5993 pMDI)=598
n (CHF 1535 pMDI)=575
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1365
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [31] | ||||||||||||||||||||||||||||||
P-value |
< 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
0.103
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.069 | ||||||||||||||||||||||||||||||
upper limit |
0.137 | ||||||||||||||||||||||||||||||
Notes [31] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||||||||||||||
End point title |
8_Change from pre-dose to 2-hour post-dose value of FEV1 at all study visits | |||||||||||||||||||||||||||
End point description |
Change from pre-dose to 2-hour post-dose value of FEV1 at all study visits.
The number of patients shown represents the ITT population; change from baseline for available patients at the specified week (Wk) for the comparison of CHF 5993 pMDI vs CHF 1535 pMDI.
Shown are the number of subjects included in the ITT population and the number of subjects with available results at the indicated week (Wk).
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Pre-dose to 2-hour post-dose at each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [32] - ITT population Wk 04 n=674 Wk 12 n=658 Wk 26 n=632 Wk 40 n=616 Wk 52 n=599 [33] - ITT population Wk 04 n=661 Wk 12 n=648 Wk 26 n=610 Wk 40 n=591 Wk 52 n=575 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1355.
n (CHF 5993 pMDI)=674
n (CHF 1535 pMDI)=661
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [34] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.046
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.029 | |||||||||||||||||||||||||||
upper limit |
0.064 | |||||||||||||||||||||||||||
Notes [34] - Analysis is based on an ANCOVA model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and the pre-dose value at the visit as a covariate. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1306.
n (CHF 5993 pMDI)=658
n (CHF 1535 pMDI)=648
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [35] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.045
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.029 | |||||||||||||||||||||||||||
upper limit |
0.062 | |||||||||||||||||||||||||||
Notes [35] - Analysis is based on an ANCOVA model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and the pre-dose value at the visit as a covariate. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1242.
n (CHF 5993 pMDI)=632
n (CHF 1535 pMDI)=610
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [36] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.031
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.015 | |||||||||||||||||||||||||||
upper limit |
0.047 | |||||||||||||||||||||||||||
Notes [36] - Analysis is based on an ANCOVA model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and the pre-dose value at the visit as a covariate. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1207.
n (CHF 5993 pMDI)=616
n (CHF 1535 pMDI)=591
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [37] | |||||||||||||||||||||||||||
P-value |
= 0.013 | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.022
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.005 | |||||||||||||||||||||||||||
upper limit |
0.039 | |||||||||||||||||||||||||||
Notes [37] - Analysis is based on an ANCOVA model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and the pre-dose value at the visit as a covariate. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1174.
n (CHF 5993 pMDI)=599
n (CHF 1535 pMDI)=575
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [38] | |||||||||||||||||||||||||||
P-value |
< 0.001 | |||||||||||||||||||||||||||
Method |
ANCOVA | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.034
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.016 | |||||||||||||||||||||||||||
upper limit |
0.052 | |||||||||||||||||||||||||||
Notes [38] - Analysis is based on an ANCOVA model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and the pre-dose value at the visit as a covariate. |
|
||||||||||||||||||||||||||||
End point title |
9_TDI focal score at all study visits | |||||||||||||||||||||||||||
End point description |
TDI focal score is a symptom-based variable, used to assess breathlessness and the impact of intervention. The BDI/TDI is a clinical rating method based on a validated instrument, developed to measure the impact of dyspnoea on three domains: functional impairment, magnitude of task, and magnitude of effort.
The BDI scores range from 0 (very severe impairment) to 4 (no impairment) for each domain with the baseline focal score consisting of the sum of each domain (i.e. from 0 to 12). Change from baseline in dyspnoea severity was measured using the TDI. TDI score ranges from -3 (major deterioration) to +3 (major improvement) for each domain with the TDI focal score consisting in the sum of each domain (i.e. from -9 to +9).
BDI and TDI are based on validated questionnaires. BDI focal score is the baseline value from which TDI focal score is assessed.
BDI=Baseline Dyspnoea Index
TDI=Transition Dyspnoea Index
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [39] - ITT population (analysed) Wk 04 n=680 Wk 12 n=661 Wk 26 n=642 Wk 40 n=622 Wk 52 n=608 [40] - ITT population (analysed) Wk 04 n=672 Wk 12 n=651 Wk 26 n=619 Wk 40 n=596 Wk 52 n=579 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments for TDI focal score at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1352:
n (CHF 5993 pMDI)=680
n (CHF 1535 pMDI)=672
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [41] | |||||||||||||||||||||||||||
P-value |
= 0.002 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.41
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.15 | |||||||||||||||||||||||||||
upper limit |
0.68 | |||||||||||||||||||||||||||
Notes [41] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments for TDI focal score at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1312:
n (CHF 5993 pMDI)=661
n (CHF 1535 pMDI)=651
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [42] | |||||||||||||||||||||||||||
P-value |
= 0.007 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.38
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
0.11 | |||||||||||||||||||||||||||
upper limit |
0.66 | |||||||||||||||||||||||||||
Notes [42] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments for TDI focal score at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1261:
n (CHF 5993 pMDI)=642
n (CHF 1535 pMDI)=619
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [43] | |||||||||||||||||||||||||||
P-value |
= 0.16 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.21
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-0.08 | |||||||||||||||||||||||||||
upper limit |
0.51 | |||||||||||||||||||||||||||
Notes [43] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments for TDI focal score at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1218:
n (CHF 5993 pMDI)=622
n (CHF 1535 pMDI)=596
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [44] | |||||||||||||||||||||||||||
P-value |
= 0.343 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.15
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-0.16 | |||||||||||||||||||||||||||
upper limit |
0.45 | |||||||||||||||||||||||||||
Notes [44] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean differences between treatments for TDI focal score at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1367) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1187:
n (CHF 5993 pMDI)=608
n (CHF 1535 pMDI)=579
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [45] | |||||||||||||||||||||||||||
P-value |
= 0.186 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
0.21
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-0.1 | |||||||||||||||||||||||||||
upper limit |
0.53 | |||||||||||||||||||||||||||
Notes [45] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||
End point title |
10_TDI response (focal score ≥1) at Week 26 and Week 52 | |||||||||||||||
End point description |
TDI response is defined as a TDI focal score ≥1. If the TDI focal score was <1, the patient was classified as a non-responder in terms of TDI. Patients with missing TDI focal score at the relevant time points were also classed as non-responders.
Results are shown as the number of responders for the comparison of CHF 5993 pMDI vs CHF 1535 pMDI.
TDI=Transition Dyspnoea Index
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Week 26, Week 52.
|
|||||||||||||||
|
||||||||||||||||
Notes [46] - ITT population [47] - ITT population |
||||||||||||||||
Statistical analysis title |
Between group analysis (TDI score ≥1, Week 26) | |||||||||||||||
Statistical analysis description |
Between treatment group analysis for subjects with a TDI focal score ≥1 at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [48] | |||||||||||||||
P-value |
= 0.027 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.28
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.029 | |||||||||||||||
upper limit |
1.594 | |||||||||||||||
Notes [48] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as factors and the baseline TDI focal score value as a covariate. |
||||||||||||||||
Statistical analysis title |
Between group analysis (TDI score ≥1, Week 52) | |||||||||||||||
Statistical analysis description |
Between treatment group analysis for subjects with a TDI focal score ≥1 at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [49] | |||||||||||||||
P-value |
= 0.43 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.093
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
0.877 | |||||||||||||||
upper limit |
1.362 | |||||||||||||||
Notes [49] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as factors and the baseline TDI focal score value as a covariate. |
|
||||||||||||||||||||||||||||
End point title |
11_Change from baseline in Saint George’s respiratory questionnaire (SGRQ) at all study visits: Total Score | |||||||||||||||||||||||||||
End point description |
SGRQ Total Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
In this study, the Total Score for SGRQ was calculated, whereby lower scores correspond to better health. Moreover, 3 component scores of SGRQ were calculated: Symptoms, Activity, and Impacts on daily life.
Change from baseline in SGRQ Total Score was calculated and presented for this end point.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
SGRQ=Saint George’s respiratory questionnaire
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [50] - ITT population (analysed) Wk 04 n=628 Wk 12 n=601 Wk 26 n=594 Wk 40 n=572 Wk 52 n=559 [51] - ITT population (analysed) Wk 04 n=607 Wk 12 n=597 Wk 26 n=558 Wk 40 n=545 Wk 52 n=532 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1302) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1235:
n (CHF 5993 pMDI)=628
n (CHF 1535 pMDI)=607
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1302
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [52] | |||||||||||||||||||||||||||
P-value |
= 0.007 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.47
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.54 | |||||||||||||||||||||||||||
upper limit |
-0.39 | |||||||||||||||||||||||||||
Notes [52] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1302) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1198:
n (CHF 5993 pMDI)=601
n (CHF 1535 pMDI)=597
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1302
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [53] | |||||||||||||||||||||||||||
P-value |
= 0.002 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-2.04
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.3 | |||||||||||||||||||||||||||
upper limit |
-0.78 | |||||||||||||||||||||||||||
Notes [53] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1302) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1152:
n (CHF 5993 pMDI)=594
n (CHF 1535 pMDI)=558
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1302
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [54] | |||||||||||||||||||||||||||
P-value |
= 0.051 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.33
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.66 | |||||||||||||||||||||||||||
upper limit |
0.01 | |||||||||||||||||||||||||||
Notes [54] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1302) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1117:
n (CHF 5993 pMDI)=572
n (CHF 1535 pMDI)=545
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1302
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [55] | |||||||||||||||||||||||||||
P-value |
= 0.057 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.4
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.85 | |||||||||||||||||||||||||||
upper limit |
0.04 | |||||||||||||||||||||||||||
Notes [55] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1302) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1091:
n (CHF 5993 pMDI)=559
n (CHF 1535 pMDI)=532
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1302
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [56] | |||||||||||||||||||||||||||
P-value |
= 0.029 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.69
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.2 | |||||||||||||||||||||||||||
upper limit |
-0.17 | |||||||||||||||||||||||||||
Notes [56] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||||||||||||||
End point title |
12_Change from baseline in Saint George’s respiratory questionnaire (SGRQ) at all study visits: Symptoms Score | |||||||||||||||||||||||||||
End point description |
SGRQ Symptoms Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patient at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
In this study, the Total Score for SGRQ was calculated, whereby lower scores correspond to better health. Moreover, 3 component scores of SGRQ were calculated: Symptoms, Activity, and Impacts on daily life.
Change from baseline in SGRQ Symptoms Score was calculated and presented for this end point.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
SGRQ=Saint George’s respiratory questionnaire
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [57] - ITT population (analysed) Wk 04 n=652 Wk 12 n=636 Wk 26 n=620 Wk 40 n=601 Wk 52 n=584 [58] - ITT population (analysed) Wk 04 n=637 Wk 12 n=629 Wk 26 n=589 Wk 40 n=576 Wk 52 n=558 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1338) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1289:
n (CHF 5993 pMDI)=652
n (CHF 1535 pMDI)=637
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment B - fixed combination CHF 1535 100/6μg v Treatment A - fixed combination CHF 5993 100/6/12.5μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1338
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [59] | |||||||||||||||||||||||||||
P-value |
= 0.126 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.19
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.72 | |||||||||||||||||||||||||||
upper limit |
0.34 | |||||||||||||||||||||||||||
Notes [59] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1338) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1265:
n (CHF 5993 pMDI)=636
n (CHF 1535 pMDI)=629
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1338
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [60] | |||||||||||||||||||||||||||
P-value |
= 0.54 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-0.53
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.24 | |||||||||||||||||||||||||||
upper limit |
1.17 | |||||||||||||||||||||||||||
Notes [60] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1338) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1209:
n (CHF 5993 pMDI)=620
n (CHF 1535 pMDI)=589
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1338
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [61] | |||||||||||||||||||||||||||
P-value |
= 0.077 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.63
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.44 | |||||||||||||||||||||||||||
upper limit |
0.17 | |||||||||||||||||||||||||||
Notes [61] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1338) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1177:
n (CHF 5993 pMDI)=601
n (CHF 1535 pMDI)=576
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1338
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [62] | |||||||||||||||||||||||||||
P-value |
= 0.224 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.23
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.21 | |||||||||||||||||||||||||||
upper limit |
0.75 | |||||||||||||||||||||||||||
Notes [62] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1338) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1142:
n (CHF 5993 pMDI)=584
n (CHF 1535 pMDI)=558
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1338
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [63] | |||||||||||||||||||||||||||
P-value |
= 0.364 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-0.96
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.03 | |||||||||||||||||||||||||||
upper limit |
1.11 | |||||||||||||||||||||||||||
Notes [63] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||||||||||||||
End point title |
13_Change from baseline in Saint George’s respiratory questionnaire (SGRQ) at all study visits: Impacts Score | |||||||||||||||||||||||||||
End point description |
SGRQ Impacts Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patients at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
In this study, the Total Score for SGRQ was calculated, whereby lower scores correspond to better health. Moreover, 3 component scores of SGRQ were calculated: Symptoms, Activity, and Impacts on daily life.
Change from baseline in SGRQ Impacts Score was calculated and presented for this end point.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
SGRQ=Saint George’s respiratory questionnaire
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [64] - ITT population (analysed) Wk 04 n=668 Wk 12 n=641 Wk 26 n=627 Wk 40 n=608 Wk 52 n=590 [65] - ITT population (analysed) Wk 04 n=654 Wk 12 n=636 Wk 26 n=594 Wk 40 n=576 Wk 52 n=559 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1346) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1322:
n (CHF 5993 pMDI)=668
n (CHF 1535 pMDI)=654
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1346
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [66] | |||||||||||||||||||||||||||
P-value |
= 0.077 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.15
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.43 | |||||||||||||||||||||||||||
upper limit |
0.13 | |||||||||||||||||||||||||||
Notes [66] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1346) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1277:
n (CHF 5993 pMDI)=641
n (CHF 1535 pMDI)=636
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1346
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [67] | |||||||||||||||||||||||||||
P-value |
= 0.01 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.93
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.4 | |||||||||||||||||||||||||||
upper limit |
-0.46 | |||||||||||||||||||||||||||
Notes [67] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1346) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1221:
n (CHF 5993 pMDI)=627
n (CHF 1535 pMDI)=594
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1346
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [68] | |||||||||||||||||||||||||||
P-value |
= 0.079 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.39
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.93 | |||||||||||||||||||||||||||
upper limit |
0.16 | |||||||||||||||||||||||||||
Notes [68] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1346) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1284:
n (CHF 5993 pMDI)=608
n (CHF 1535 pMDI)=576
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1346
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [69] | |||||||||||||||||||||||||||
P-value |
= 0.054 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.58
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.19 | |||||||||||||||||||||||||||
upper limit |
0.03 | |||||||||||||||||||||||||||
Notes [69] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1346) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1149:
n (CHF 5993 pMDI)=590
n (CHF 1535 pMDI)=559
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1346
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [70] | |||||||||||||||||||||||||||
P-value |
= 0.015 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-2.09
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.76 | |||||||||||||||||||||||||||
upper limit |
-0.41 | |||||||||||||||||||||||||||
Notes [70] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||||||||||||||
End point title |
14_Change from baseline in Saint George’s respiratory questionnaire (SGRQ) at all study visits: Activity Score | |||||||||||||||||||||||||||
End point description |
SGRQ Activity Score.
SGRQ is a questionnaire developed to measure health in chronic airflow limitation.
SGRQ questionnaire was completed by the patients at all study visits (Week 0 baseline, 4, 12, 26, 40, 52).
In this study, the Total Score for SGRQ was calculated, whereby lower scores correspond to better health. Moreover, 3 component scores of SGRQ were calculated: Symptoms, Activity, and Impacts on daily life.
Change from baseline in SGRQ Activity Score was calculated and presented for this end point.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
SGRQ=Saint George’s respiratory questionnaire
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline and each study visit (Week 4, 12, 26, 40, 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [71] - ITT population (analysed) Wk 04 n=659 Wk 12 n=626 Wk 26 n=616 Wk 40 n=596 Wk 52 n=583 [72] - ITT population (analysed) Wk 4 n=639 Wk 12 n=621 Wk 26 n=585 Wk 40 n=562 Wk 52 n=554 |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 4 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 4.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1333) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1298:
n (CHF 5993 pMDI)=659
n (CHF 1535 pMDI)=639
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1333
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [73] | |||||||||||||||||||||||||||
P-value |
= 0.034 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.48
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-2.84 | |||||||||||||||||||||||||||
upper limit |
-0.11 | |||||||||||||||||||||||||||
Notes [73] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 12 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 12.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1333) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1247:
n (CHF 5993 pMDI)=626
n (CHF 1535 pMDI)=621
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1333
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [74] | |||||||||||||||||||||||||||
P-value |
= 0.001 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-2.57
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-4.14 | |||||||||||||||||||||||||||
upper limit |
-1.01 | |||||||||||||||||||||||||||
Notes [74] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 26 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 26.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1333) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1201:
n (CHF 5993 pMDI)=616
n (CHF 1535 pMDI)=585
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1333
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [75] | |||||||||||||||||||||||||||
P-value |
= 0.039 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.71
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.33 | |||||||||||||||||||||||||||
upper limit |
-0.09 | |||||||||||||||||||||||||||
Notes [75] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 40 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 40.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1333) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1158:
n (CHF 5993 pMDI)=596
n (CHF 1535 pMDI)=562
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1333
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [76] | |||||||||||||||||||||||||||
P-value |
= 0.065 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.61
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.32 | |||||||||||||||||||||||||||
upper limit |
-0.1 | |||||||||||||||||||||||||||
Notes [76] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups Wk 52 | |||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups at Week 52.
CHF 5993 pMDI vs CHF 1535 pMDI
The number of subjects in this analysis shown (1333) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1158:
n (CHF 5993 pMDI)=596
n (CHF 1535 pMDI)=562
|
|||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||||||||||||||
Number of subjects included in analysis |
1333
|
|||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||||||||
Analysis type |
superiority [77] | |||||||||||||||||||||||||||
P-value |
= 0.145 | |||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | |||||||||||||||||||||||||||
Point estimate |
-1.31
|
|||||||||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||||||||
level |
95% | |||||||||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||||||||
lower limit |
-3.08 | |||||||||||||||||||||||||||
upper limit |
0.45 | |||||||||||||||||||||||||||
Notes [77] - Analysis is based on a linear mixed model for repeated measures including treatment, visit, treatment by visit interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by visit interaction as covariates. |
|
||||||||||||||||
End point title |
15_SGRQ response (change from baseline in Total score ≤-4) at Week 26 and Week 52 | |||||||||||||||
End point description |
SGRQ response is defined as a change from baseline in SGRQ total score ≤ -4. If the change from baseline was > -4, the patient was classed as a non-responder in terms of SGRQ. Patients with missing change from baseline at the relevant time points were also classified as non-responders.
Results are shown as the number of responders for the comparison of CHF 5993 pMDI vs CHF 1535 pMDI.
SGRQ=Saint George’s respiratory questionnaire
|
|||||||||||||||
End point type |
Secondary
|
|||||||||||||||
End point timeframe |
Baseline to Week 26, Week 52.
|
|||||||||||||||
|
||||||||||||||||
Notes [78] - ITT population [79] - ITT population |
||||||||||||||||
Statistical analysis title |
Btw grp analysis, change in SGRQ score ≤-4, Wk 26 | |||||||||||||||
Statistical analysis description |
SGRQ response = Subjects with a change from baseline in Total Score ≤-4, at week 26.
Between group analysis (change from baseline in SGRQ Total score ≤-4, Week 26).
CHF 5993 pMDI / CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [80] | |||||||||||||||
P-value |
< 0.001 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.521
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.211 | |||||||||||||||
upper limit |
1.911 | |||||||||||||||
Notes [80] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as factors and the baseline SGRQ total score value as a covariate. |
||||||||||||||||
Statistical analysis title |
Btw grp analysis, change in SGRQ score ≤-4, Wk 52 | |||||||||||||||
Statistical analysis description |
SGRQ response = Subjects with a change from baseline in Total Score ≤-4, at week 52.
Between group analysis (change from baseline in SGRQ Total score ≤-4, Week 52).
CHF 5993 pMDI / CHF 1535 pMDI
|
|||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||||||||
Number of subjects included in analysis |
1367
|
|||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||
Analysis type |
superiority [81] | |||||||||||||||
P-value |
= 0.014 | |||||||||||||||
Method |
Logistic model | |||||||||||||||
Parameter type |
Odds ratio (OR) | |||||||||||||||
Point estimate |
1.327
|
|||||||||||||||
Confidence interval |
||||||||||||||||
level |
95% | |||||||||||||||
sides |
2-sided
|
|||||||||||||||
lower limit |
1.06 | |||||||||||||||
upper limit |
1.661 | |||||||||||||||
Notes [81] - Analysis is based on a logistic model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as factors and the baseline SGRQ total score value as a covariate. |
|
|||||||||||||||||||||||||||||||
End point title |
16_Change from baseline for percentage of days without intake of rescue medication | ||||||||||||||||||||||||||||||
End point description |
Days without intake of rescue medication.
Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the percentage of days without intake of rescue medication.
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [82] - ITT population W 1-4 n=645 W 5-12 n=642 W 13-26 n=627 W 27-40 n=601 W 41-52 n=578 W 1-52 n=650 [83] - ITT population W 1-4 n=637 W 5-12 n=629 W 13-26 n=610 W 27-40 n=572 W 41-52 n=552 W 1-52 n=640 |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 1-4 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 1-4.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1282:
n (CHF 5993 pMDI)=645
n (CHF 1535 pMDI)=637
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [84] | ||||||||||||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
4.21
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
1.69 | ||||||||||||||||||||||||||||||
upper limit |
6.73 | ||||||||||||||||||||||||||||||
Notes [84] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 5-12 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 5-12.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1271:
n (CHF 5993 pMDI)=642
n (CHF 1535 pMDI)=629
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [85] | ||||||||||||||||||||||||||||||
P-value |
= 0.039 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
3.05
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
0.15 | ||||||||||||||||||||||||||||||
upper limit |
5.95 | ||||||||||||||||||||||||||||||
Notes [85] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 13-26 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 13-26.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1237:
n (CHF 5993 pMDI)=627
n (CHF 1535 pMDI)=610
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [86] | ||||||||||||||||||||||||||||||
P-value |
= 0.051 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
3.09
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.02 | ||||||||||||||||||||||||||||||
upper limit |
6.2 | ||||||||||||||||||||||||||||||
Notes [86] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 27-40 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 27-40.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1173:
n (CHF 5993 pMDI)=601
n (CHF 1535 pMDI)=572
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [87] | ||||||||||||||||||||||||||||||
P-value |
= 0.342 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
1.6
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-1.71 | ||||||||||||||||||||||||||||||
upper limit |
4.91 | ||||||||||||||||||||||||||||||
Notes [87] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 41-52 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 41-52.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1130:
n (CHF 5993 pMDI)=578
n (CHF 1535 pMDI)=552
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [88] | ||||||||||||||||||||||||||||||
P-value |
= 0.134 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
2.59
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.8 | ||||||||||||||||||||||||||||||
upper limit |
5.97 | ||||||||||||||||||||||||||||||
Notes [88] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 1-52 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 1-52.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1290:
n (CHF 5993 pMDI)=650
n (CHF 1535 pMDI)=640
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [89] | ||||||||||||||||||||||||||||||
P-value |
= 0.063 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
2.65
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.14 | ||||||||||||||||||||||||||||||
upper limit |
5.45 | ||||||||||||||||||||||||||||||
Notes [89] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|
|||||||||||||||||||||||||||||||
End point title |
17_Change from baseline for the average use of rescue medication | ||||||||||||||||||||||||||||||
End point description |
Average use of rescue medication.
Change from baseline to each inter-visit period and for the entire treatment period (Week 1-52) in the average use of rescue medication (number of puffs/day).
Shown are the number of subjects included in the model and the number of subjects with available results at the indicated week (Wk).
|
||||||||||||||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52.
|
||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||
Notes [90] - ITT population W 1-4 n=645 W 5-12 n=642 W 13-26 n=627 W 27-40 n=601 W 41-52 n=578 W 1-52 n=650 [91] - ITT population W 1-4 n=637 W 5-12 n=629 W 13-26 n=610 W 27-40 n=572 W 41-52 n=552 W 1-52 n=640 |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 1-4 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 1-4.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1282:
n (CHF 5993 pMDI)=645
n (CHF 1535 pMDI)=637
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [92] | ||||||||||||||||||||||||||||||
P-value |
= 0.001 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.21
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.34 | ||||||||||||||||||||||||||||||
upper limit |
-0.08 | ||||||||||||||||||||||||||||||
Notes [92] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 5-12 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 5-12.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1271:
n (CHF 5993 pMDI)=642
n (CHF 1535 pMDI)=629
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [93] | ||||||||||||||||||||||||||||||
P-value |
= 0.016 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.19
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.35 | ||||||||||||||||||||||||||||||
upper limit |
-0.04 | ||||||||||||||||||||||||||||||
Notes [93] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 13-26 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 13-26.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1237:
n (CHF 5993 pMDI)=627
n (CHF 1535 pMDI)=610
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [94] | ||||||||||||||||||||||||||||||
P-value |
= 0.029 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.19
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.35 | ||||||||||||||||||||||||||||||
upper limit |
-0.02 | ||||||||||||||||||||||||||||||
Notes [94] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 27-40 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 27-40.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1173:
n (CHF 5993 pMDI)=601
n (CHF 1535 pMDI)=572
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [95] | ||||||||||||||||||||||||||||||
P-value |
= 0.225 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.11
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.29 | ||||||||||||||||||||||||||||||
upper limit |
0.07 | ||||||||||||||||||||||||||||||
Notes [95] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 41-52 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 41-52.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1130:
n (CHF 5993 pMDI)=578
n (CHF 1535 pMDI)=552
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [96] | ||||||||||||||||||||||||||||||
P-value |
= 0.262 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.11
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.3 | ||||||||||||||||||||||||||||||
upper limit |
0.08 | ||||||||||||||||||||||||||||||
Notes [96] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|||||||||||||||||||||||||||||||
Statistical analysis title |
Adjusted mean difference btw treat groups W 1-52 | ||||||||||||||||||||||||||||||
Statistical analysis description |
Adjusted mean difference between treatment groups during Week 1-52.
CHF 5993 pMDI - CHF 1535 pMDI
The number of subjects in this analysis shown (1298) is due to an innate error within the EudraCT database. The correct number of participating subjects is shown below.
The total number of subjects with available data in this analysis is 1290:
n (CHF 5993 pMDI)=650
n (CHF 1535 pMDI)=640
|
||||||||||||||||||||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||||||||||||||||||||
Number of subjects included in analysis |
1298
|
||||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||||
Analysis type |
superiority [97] | ||||||||||||||||||||||||||||||
P-value |
= 0.062 | ||||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||||||||||||||||||||
Point estimate |
-0.15
|
||||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||||
lower limit |
-0.31 | ||||||||||||||||||||||||||||||
upper limit |
0.01 | ||||||||||||||||||||||||||||||
Notes [97] - Analysis is based on a linear mixed model for repeated measures including treatment, inter-visit period, treatment by inter-visit period interaction, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at screening as fixed effects, and baseline value and baseline by inter-visit period interaction as covariates. |
|
|||||||||||||
End point title |
18_Moderate and severe COPD exacerbation rate over 52 weeks of treatment | ||||||||||||
End point description |
Rate of moderate or severe COPD exacerbation.
Evaluate the rate of moderate or severe COPD exacerbation over 52 weeks of treatment.
Data are presented as Adjusted Exacerbation Rate per Patient per Year (95% CI).
Shown are the number of subjects included in the model and the number of subjects with available results.
COPD=Chronic obstructive pulmonary disease
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline to Week 52 (entire treatment period).
|
||||||||||||
|
|||||||||||||
Notes [98] - ITT population [99] - ITT population |
|||||||||||||
Statistical analysis title |
Adjusted rate ratio for mod and sev exacerbations | ||||||||||||
Statistical analysis description |
Adjusted rate ratio for moderate and severe exacerbations.
CHF 5993 pMDI / CHF 1535 pMDI
|
||||||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
||||||||||||
Number of subjects included in analysis |
1367
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority [100] | ||||||||||||
P-value |
= 0.005 | ||||||||||||
Method |
Negative binomial model | ||||||||||||
Parameter type |
Adjusted Rate Ratio | ||||||||||||
Point estimate |
0.773
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
0.647 | ||||||||||||
upper limit |
0.924 | ||||||||||||
Notes [100] - Analysis is based on a negative binomial model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as fixed effects, and log-time on study as an offset. |
|
||||||||||
End point title |
19_Time to first moderate or severe COPD exacerbation | |||||||||
End point description |
Time to first moderate or severe COPD exacerbation.
Shown are the number of subjects included in the model and the number of subjects with available results.
COPD=Chronic obstructive pulmonary disease
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Baseline to Week 52 (entire treatment period).
|
|||||||||
|
||||||||||
Notes [101] - ITT population [102] - ITT population |
||||||||||
Statistical analysis title |
Time to first moderate or severe COPD exacerbation | |||||||||
Comparison groups |
Treatment A - fixed combination CHF 5993 100/6/12.5μg v Treatment B - fixed combination CHF 1535 100/6μg
|
|||||||||
Number of subjects included in analysis |
1358
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority [103] | |||||||||
P-value |
= 0.02 | |||||||||
Method |
Cox proportional hazards model | |||||||||
Parameter type |
Hazard ratio (HR) | |||||||||
Point estimate |
0.803
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
0.668 | |||||||||
upper limit |
0.967 | |||||||||
Notes [103] - Analysis is based on a Cox proportional hazards model including treatment, country, number of COPD exacerbations in the previous year, severity of airflow limitation and smoking status at Screening as factors. CHF 5993 pMDI / CHF 1535 pMDI |
|
||||||||||||||||||||||||||||
End point title |
20_Vital signs: Systolic blood pressure | |||||||||||||||||||||||||||
End point description |
Systolic Blood Pressure.
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [104] - Safety pop W 0 post n=683 W 26 pre n=643 W 26 post n=633 W 52 pre n=608 W 52 post n=603 [105] - Safety pop W 0 post n=679 W 26 pre n=619 W 26 post n=612 W 52 pre n=579 W 52 post n=576 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
21_Vital signs: Diastolic blood pressure | |||||||||||||||||||||||||||
End point description |
Diastolic Blood Pressure.
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [106] - Safety pop W 0 post n=683 W 26 pre n=643 W 26 post n=633 W 52 pre n=608 W 52 post n=603 [107] - Safety pop W 0 post n=679 W 26 pre n=619 W 26 post n=612 W 52 pre n=579 W 52 post n=576 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
22_Vital signs: Body mass index | ||||||||||||||||||
End point description |
Body Mass Index.
Results represent changes from baseline (Week 0), on Week 26 and Week 52.
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [108] - Safety population Wk 26 n=643 Wk 52 n=608 [109] - Safety population Wk 26 n=620 Wk 52 n=579 |
|||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
23_Electrocardiogram parameters: Heart rate | |||||||||||||||||||||||||||
End point description |
Heart Rate.
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [110] - Safety pop W 0 post n=658 W 26 pre n=618 W 26 post n=611 W 52 pre n=588 W 52 post n=583 [111] - Safety pop W 0 post n=656 W 26 pre n=597 W 26 post n=592 W 52 pre n=557 W 52 post n=554 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
24_Electrocardiogram parameters: QTcF interval | |||||||||||||||||||||||||||
End point description |
QTcF (Fridericia’s Corrected QT Interval).
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [112] - Safety pop W 0 post n=657 W 26 pre n=618 W 26 post n=611 W 52 pre n=589 W 52 post n=583 [113] - Safety pop W 0 post n=656 W 26 pre n=597 W 26 post n=592 W 52 pre n=557 W 52 post n=554 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
25_Electrocardiogram parameters: PR interval | |||||||||||||||||||||||||||
End point description |
PR Interval.
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [114] - Safety pop W 0 post n=658 W 26 pre n=618 W 26 post n=611 W 52 pre n=589 W 52 post n=583 [115] - Safety pop W 0 post n=656 W 26 pre n=597 W 26 post n=592 W 52 pre n=557 W 52 post n=554 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
||||||||||||||||||||||||||||
End point title |
26_Electrocardiogram parameters: QRS interval | |||||||||||||||||||||||||||
End point description |
QRS interval.
Results represent changes from baseline (Week 0, pre-dose), on Week 26 and Week 52 (pre-dose and 10-minute post-dose).
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
|||||||||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||||||||
End point timeframe |
Baseline to Week 4, 12, 26, 40, 52 (data shown are for Week 26 and Week 52).
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
Notes [116] - Safety pop W 0 post n=658 W 26 pre n=618 W 26 post n=611 W 52 pre n=589 W 52 post n=583 [117] - Safety pop W 0 post n=656 W 26 pre n=597 W 26 post n=592 W 52 pre n=557 W 52 post n=554 |
||||||||||||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||
End point title |
27_Holter electrocardiogram parameter: 24-h Average heart rate | ||||||||||||||||||
End point description |
Holter electrocardiogram parameter: 24-h Average heart rate values.
Results represent change from baseline (Week 0, pre-dose), to Week 26 and Week 52.
Shown are the number of subjects included in the safety population and the number of subjects with available results.
|
||||||||||||||||||
End point type |
Secondary
|
||||||||||||||||||
End point timeframe |
Baseline, Week 26, Week 52.
|
||||||||||||||||||
|
|||||||||||||||||||
Notes [118] - Holter subset population Wk 26 n=60 Wk 52 n=58 [119] - Holter subset population Wk 26 n=62 Wk 52 n=56 |
|||||||||||||||||||
No statistical analyses for this end point |
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Adverse events information
|
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Timeframe for reporting adverse events |
Adverse events were reported from the time of patient informed consent signature to study completion or discontinuation.
|
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Adverse event reporting additional description |
Data represent treatment-emergent adverse events (i.e. events that occurred after the first randomised study drug intake).
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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 |
Treatment A - fixed combination CHF 5993 100/6 /12.5μg
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Treatment B - fixed combination CHF 1535 100/6μg
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
Online references |
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http://www.ncbi.nlm.nih.gov/pubmed/27598678 |