Clinical Trial Results:
Open label, prospective, exploratory study to investigate the effect of inhaled CHF5993 pMDI on central and peripheral airway dimensions in COPD patients by functional respiratory imaging
Summary
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EudraCT number |
2017-000438-79 |
Trial protocol |
BE HU |
Global end of trial date |
31 Jan 2019
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Results information
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Results version number |
v1(current) |
This version publication date |
13 Feb 2020
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First version publication date |
13 Feb 2020
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
CCD-05993AA1-16
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
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, clinicaltrials_info@chiesi.com
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Scientific contact |
Clinical Trial Transparency, Chiesi Farmaceutici S.p.A, 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 |
24 Sep 2019
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Jan 2019
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
Evaluate the effect of inhaled extrafine CHF5993 pMDI on airway volumes and resistance, by using functional respiratory imaging (FRI) in patients with chronic obstructive pulmonary disease (COPD), treated with a non extrafine extemporary triple combination for three months before entering the study.
The IMP has both bronchodilatory and anti-inflammatory properties and is used for the treatment of patients with severe COPD or with asthma. Each subject inhaled CHF5993 two times daily; total daily dose: 400 μg BDP, 24 μg FF, and 50 μg GB, for 24 weeks.
Functional Respiratory Imaging (FRI) with computational fluid dynamics (CFD) analysis was used to demonstrate the effect of the IMP on airway parameters in the distal and central regions of the lung and to image the deposition of the extrafine formulation into the deep lung. Lung imaging was obtained from computed tomography (CT) scans, taken upon inspiration and expiration.
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Protection of trial subjects |
The clinical study was performed in accordance with the principles that have their origin in the declaration of Helsinki, and with local regulations. Furthermore, the study was performed in accordance with the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) notes for guidance on Good Clinical Practice (GCP) (ICH/CPMP/135/95).
Before the start of the study, all subjects gave their written informed consent to participate in the study after having been informed of the nature and implications of the study. At completion of subject's participation in the study, it was the Investigator’s responsibility to prescribe the most appropriate treatment for the subject or to restore the initial therapy or to refer to the general practitioner.
Low-dose multislice CT scans were performed at pre-dose, at Visit 2 (Week 0), Visit 5 (Week 12), and Visit 8 (Week 24). At Visit 2, a scan of the upper airway was also performed.
Adverse events (AEs) and vital signs were recorded at all visits (from screening onward, during the treatment phase of 24 weeks). If the investigator deemed it necessary, a visit was scheduled at 7 days after the last drug administration. A follow-up call was scheduled for all subjects and it was performed 7 days after the last study drug administration.
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Background therapy |
Permitted concomitant medications 1. Inhaled salbutamol administered as rescue medication. A minimum period of 6 h had to elapse between the use of rescue salbutamol and the spirometric measurements. 2. Long-acting antihistamines if taken at stable regimen at least 2 months prior to screening or if taken pro re nata (PRN). 3. Non-selective xanthine derivatives (e.g., theophylline) if taken at stable regimen for at least 1 month prior to screening and to be maintained constant during the study. If the subject took concomitant medications, prior to the Visit 1 (screening visit), Visit 2, Visit 5, or Visit 8, the pre-specified washout periods for concomitant medications had to be respected. Abbreviations used in this entry: BDP=Beclometasone dipropionate B17MP=Beclometasone 17-monopropionate (active metabolite of BDP) CFD=Computational fluid dynamics CHF 5993=Fixed combination of BDP, FF, and GB COPD=Chronic obstructive pulmonary disease CT=Computerised tomography FEV1=Forced expiratory volume in the 1st second FF=Formoterol fumarate FRC=Functional residual capacity FRI=Functional Respiratory Imaging GB=Glycopyrronium bromide HU=Hounsfield Units IC=Inspiratory capacity kPa=Kilopascal MedDRA=Medical Dictionary for Regulatory Activities μg=Microgram PEF=Peak expiratory flow pMDI=Pressurised metered dose inhaler SGRQ=Saint George Respiratory Questionnaire RV=Residual volume s=Second TLC=Total lung capacity Voxel=Volume representing element (in Hounsfield units) is a single data point, on a regularly spaced, three-dimensional grid. | ||
Evidence for comparator |
None used. | ||
Actual start date of recruitment |
20 Nov 2017
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 14
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Country: Number of subjects enrolled |
Hungary: 7
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Worldwide total number of subjects |
21
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EEA total number of subjects |
21
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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) |
8
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From 65 to 84 years |
13
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85 years and over |
0
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Recruitment
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Recruitment details |
Adult male and female adult subjects with documented chronic obstructive pulmonary disease (COPD) for at least 12 months (GOLD, 2017 criteria), were evaluated according to the study inclusion and exclusion criteria. Signed Informed Consent Form was obtained prior to any study procedures. | ||||||||||
Pre-assignment
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Screening details |
At the screening visit (7 ± 3 days prior to baseline), subjects were selected to enter into the study according to the eligibility criteria. Overall, 32 subjects were screened; of these, 21 subjects were enrolled for treatment and evaluation. | ||||||||||
Period 1
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Period 1 title |
Treatment (overall period)
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Is this the baseline period? |
Yes | ||||||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||||||
Blinding implementation details |
Open-label study; not blinded.
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Arms
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Arm title
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Subjects with COPD | ||||||||||
Arm description |
Adult subjects with diagnosed and established COPD, who have been treated with a non-extrafine extemporary triple combination for three months, before entering the study. The aim of the study was to explore changes occurring in response to a long-term treatment with CHF 5993, which is an extrafine triple fixed-dose combination. | ||||||||||
Arm type |
Experimental | ||||||||||
Investigational medicinal product name |
CHF 5993 (100/6/12.5 μg), pMDI
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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 |
CHF 5993 is a fixed combination of BDP, FF, and GB.
Single actuation of the CHF 5993 pMDI contains: 100μg BDP/6μg FF/12.5μg GB.
Each subject inhaled CHF 5993 100/6/12.5 μg pMDI as two inhalations twice a day (two inhalations in the morning and two inhalations in the evening), giving a total daily dose of 400 μg BDP, 24 μg FF, and 50 μg GB.
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Baseline characteristics reporting groups
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Reporting group title |
Subjects with COPD
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Reporting group description |
Adult subjects with diagnosed and established COPD, who have been treated with a non-extrafine extemporary triple combination for three months, before entering the study. The aim of the study was to explore changes occurring in response to a long-term treatment with CHF 5993, which is an extrafine triple fixed-dose combination. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Subjects with COPD
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Reporting group description |
Adult subjects with diagnosed and established COPD, who have been treated with a non-extrafine extemporary triple combination for three months, before entering the study. The aim of the study was to explore changes occurring in response to a long-term treatment with CHF 5993, which is an extrafine triple fixed-dose combination. | ||
Subject analysis set title |
Baseline, FRC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at baseline; lung level FRC
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Subject analysis set title |
Week 12, FRC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at week 12; lung level FRC
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Subject analysis set title |
Week 24, FRC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at week 24; lung level FRC
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Subject analysis set title |
Baseline, TLC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at baseline; lung level TLC
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Subject analysis set title |
Week 12, TLC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at week 12; lung level TLC
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Subject analysis set title |
Week 24, TLC
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at week 24; lung level TLC
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Subject analysis set title |
Baseline
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at baseline.
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Subject analysis set title |
Week 24
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Subject analysis set type |
Per protocol | ||
Subject analysis set description |
Subjects evaluated at week 24.
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End point title |
1_Specific image-based airway volumes (siVaw); FRC and TLC | ||||||||||||||||||||||||||||
End point description |
Specific image-based airway volumes (siVaw): Computerised tomography-based (CT-based) airway volumes, normalised by the lung volume.
Percent change from baseline to week 12 and 24 of treatment. Lung level: FRC and TLC.
The primary region evaluated was the distal lung region.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Specific image-based airway volumes are the CT-based airway volumes normalised by the lung volume. The siVaw as an FRI parameter is derived from the airway volume (iVaw). Because the airway volume is dependent on the lung volume, the airway volumes had to be made specific to facilitate the comparison between the study visits. The lung volume could be determined from the CT scans for both FRC and TLC, by identifying and grouping the voxels (a value in three-dimensional space) that represent the air in the lungs. The specificity was calculated by dividing the airway volume by the lung volume.
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End point type |
Primary
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End point timeframe |
Baseline, week 12, week 24.
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Notes [1] - Per protocol population was used for all analyses groups [2] - Geometric coefficient of variation is the coefficient of variation for all analyses |
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Statistical analysis title |
1_Percent change from baseline at week 12; FRC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 12; within group comparison.
Lung level: FRC
The value N=35 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=17.
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Comparison groups |
Week 12, FRC v Baseline, FRC
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [3] | ||||||||||||||||||||||||||||
P-value |
= 0.701 [4] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
5.01
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-19.56 | ||||||||||||||||||||||||||||
upper limit |
37.08 | ||||||||||||||||||||||||||||
Notes [3] - The analysis type is a post treatment comparison versus baseline. [4] - p-value and estimates are based on a mixed model for repeated measures (MMRM) including log(baseline), visit and its interaction as effects. Estimates are based on back transformed values. |
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Statistical analysis title |
2_Percent change from baseline at week 24; FRC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=34 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=17.
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Comparison groups |
Week 24, FRC v Baseline, FRC
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Number of subjects included in analysis |
34
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Analysis specification |
Pre-specified
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Analysis type |
other [5] | ||||||||||||||||||||||||||||
P-value |
= 0.781 [6] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
3.47
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-19.97 | ||||||||||||||||||||||||||||
upper limit |
33.76 | ||||||||||||||||||||||||||||
Notes [5] - The analysis type is a post treatment comparison versus baseline. [6] - p-value and estimates are based on a mixed model for repeated measures (MMRM) including log(baseline), visit and its interaction as effects. Estimates are based on back transformed values. |
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Statistical analysis title |
3_Percent change from baseline at week 12; TLC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 12; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
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Comparison groups |
Baseline, TLC v Week 12, TLC
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other [7] | ||||||||||||||||||||||||||||
P-value |
= 0.261 [8] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
7.91
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-6 | ||||||||||||||||||||||||||||
upper limit |
23.87 | ||||||||||||||||||||||||||||
Notes [7] - The analysis type is a post treatment comparison versus baseline. [8] - p-value and estimates are based on a mixed model for repeated measures (MMRM) including log(baseline), visit and its interaction as effects. Estimates are based on back transformed values. |
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Statistical analysis title |
4_Percent change from baseline at week 24; TLC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
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Comparison groups |
Week 24, TLC v Baseline, TLC
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other [9] | ||||||||||||||||||||||||||||
P-value |
= 0.023 [10] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
15.96
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
2.33 | ||||||||||||||||||||||||||||
upper limit |
31.41 | ||||||||||||||||||||||||||||
Notes [9] - The analysis type is a post treatment comparison versus baseline. [10] - p-value and estimates are based on a mixed model for repeated measures (MMRM) including log(baseline), visit and its interaction as effects. Estimates are based on back transformed values. |
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End point title |
2_Specific image-based airway resistance (siRaw); FRC and TLC | ||||||||||||||||||||||||||||
End point description |
Specific image-based airway resistance (siRaw). Percent change from baseline to week 12 and 24 of treatment.
Lung level: FRC and TLC.
The primary region evaluated was the distal lung region. Analysis was done for the Functional Residual Capacity (FRC) and for the Total Lung Capacity (TLC). Results represent the actual values per time point for siRaw at baseline, week 12, and week 24. Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Specific image-based airway resistance is the CFD-based airway resistance normalised by the lung volume and was determined using CFD. The specific airway resistance (siRaw) as an FRI parameter is derived from the airway resistance (iRaw). Because the airway resistance is dependent on the lung volume, the airway resistance had to be made specific to facilitate the comparison between the visits.
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End point type |
Primary
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End point timeframe |
Baseline, week 12, week 24.
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Notes [11] - Per protocol population was used for all analyses groups [12] - Geometric coefficient of variation is the coefficient of variation for all analyses |
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Statistical analysis title |
1_Percent change from baseline at week 12; FRC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 12; within group comparison.
Lung level: FRC
The value N=35 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=17.
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Comparison groups |
Week 12, FRC v Baseline, FRC
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Number of subjects included in analysis |
35
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Analysis specification |
Pre-specified
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Analysis type |
other [13] | ||||||||||||||||||||||||||||
P-value |
= 0.027 [14] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
65.87
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
6.86 | ||||||||||||||||||||||||||||
upper limit |
157.44 | ||||||||||||||||||||||||||||
Notes [13] - The analysis type is a post treatment comparison versus baseline; see also 'Analysis type comment' for end point 1. [14] - Further clarification is provided in the 'P-value comment' for end point 1. |
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Statistical analysis title |
2_Percent change from baseline at week 24; FRC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
Lung level: FRC
The value N=34 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=17.
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Comparison groups |
Week 24, FRC v Baseline, FRC
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Number of subjects included in analysis |
34
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Analysis specification |
Pre-specified
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Analysis type |
other [15] | ||||||||||||||||||||||||||||
P-value |
= 0.104 [16] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
62.84
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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lower limit |
-10.64 | ||||||||||||||||||||||||||||
upper limit |
196.72 | ||||||||||||||||||||||||||||
Notes [15] - The analysis type is a post treatment comparison versus baseline; see also 'Analysis type comment' for end point 1. [16] - Further clarification is provided in the 'P-value comment' for end point 1. |
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Statistical analysis title |
3_Percent change from baseline at week 12; TLC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
Lung level: TLC
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
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Comparison groups |
Week 12, TLC v Baseline, TLC
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Number of subjects included in analysis |
39
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Analysis specification |
Pre-specified
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Analysis type |
other [17] | ||||||||||||||||||||||||||||
P-value |
= 0.052 [18] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
-27.35
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Confidence interval |
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level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
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||||||||||||||||||||||||||||
lower limit |
-47.4 | ||||||||||||||||||||||||||||
upper limit |
0.36 | ||||||||||||||||||||||||||||
Notes [17] - The analysis type is a post treatment comparison versus baseline; see also 'Analysis type comment' for end point 1. [18] - Further clarification is provided in the 'P-value comment' for end point 1. |
|||||||||||||||||||||||||||||
Statistical analysis title |
4_Percent change from baseline at week 24; TLC | ||||||||||||||||||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
Lung level: TLC
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||||||||||||||||||
Comparison groups |
Week 24, TLC v Baseline, TLC
|
||||||||||||||||||||||||||||
Number of subjects included in analysis |
39
|
||||||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||||||
Analysis type |
other [19] | ||||||||||||||||||||||||||||
P-value |
= 0.05 [20] | ||||||||||||||||||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||||||||||||||||||
Point estimate |
-30.81
|
||||||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||||||
lower limit |
-52.17 | ||||||||||||||||||||||||||||
upper limit |
0.08 | ||||||||||||||||||||||||||||
Notes [19] - The analysis type is a post treatment comparison versus baseline; see also 'Analysis type comment' for end point 1. [20] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
3_Internal Airflow Distribution | ||||||||||||
End point description |
Internal airflow distribution (Internal lobar airflow distribution).
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Lobar volume (iVlobe) is an FRI-based ventilation parameter, obtained by identifying and grouping voxels that represent the air in the lungs. The lung volume could be determined from the scans at both FRC and TLC. The subject-specific airflow distribution could be established by assessing lobar volume expansion.
Results represent the actual values per time point, at baseline and week 24.
Lung level: Not applicable
Lung region: Upper lobes
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [21] - Per protocol population was used for all analyses groups [22] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=37 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
37
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [23] | ||||||||||||
P-value |
= 0.858 [24] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
-0.62
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-7.56 | ||||||||||||
upper limit |
6.84 | ||||||||||||
Notes [23] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [24] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
4_Air Trapping | ||||||||||||
End point description |
Air trapping.
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Air trapping, also called gas trapping, is an abnormal retention of air in the lungs. It is observed in obstructive lung diseases such as asthma and bronchiolitis obliterans syndrome, and in chronic obstructive pulmonary diseases such as emphysema and chronic bronchitis. FRI-based air trapping was defined as all the intrapulmonary voxels with Hounsfield Units (HU) between -1024 and -850, using the expiratory scans at FRC.
Results represent the actual values per time point, at baseline and week 24.
Lung level: FRC
Lung region: Total lung region
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [25] - Per protocol population was used for all analyses groups [26] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=37 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
37
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [27] | ||||||||||||
P-value |
= 0.693 [28] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
1.79
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-7.28 | ||||||||||||
upper limit |
11.75 | ||||||||||||
Notes [27] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [28] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
5_Emphysema (Low Attenuation Score) | ||||||||||||
End point description |
Emphysema (Low Attenuation Score)
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
The low attenuation areas on CT scans have been reported to represent emphysematous changes of the lung. Emphysema is a long-term, progressive disease of the lungs that primarily causes shortness of breath due to over-inflation of the alveoli. FRI-based emphysema calculations were defined as all the intrapulmonary voxels with HU between -1024 and -950, using the inspiratory scans at TLC.
Results represent the actual values per time point, at baseline and week 24.
Lung level: TLC
Lung region: Total lung region
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [29] - Per protocol population was used for all analyses groups [30] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
39
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [31] | ||||||||||||
P-value |
= 0.603 [32] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
-5.47
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-24.4 | ||||||||||||
upper limit |
18.21 | ||||||||||||
Notes [31] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [32] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
6_Airway Wall Volume | ||||||||||||
End point description |
Airway wall volume.
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
The airway wall volume (iVaww) consisted of all visible tissue in the CT scan that encompassed the airway wall. The airway wall volume can typically be described to the same generation level as the volume description of the airway lumen. This is where the airway diameter is around 1 2 mm.
Results represent the actual values per time point, at baseline and week 24.
Lung level: TLC
Lung region: Distal lung region
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [33] - Per protocol population was used for all analyses groups [34] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an
innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||
Comparison groups |
Baseline v Week 24
|
||||||||||||
Number of subjects included in analysis |
39
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [35] | ||||||||||||
P-value |
= 0.169 [36] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
6.02
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.7 | ||||||||||||
upper limit |
15.52 | ||||||||||||
Notes [35] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [36] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
7_Blood Vessel Density | ||||||||||||
End point description |
Blood vessel density.
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Blood vessel density (iVbv) was determined through segmentation and 3D reconstruction of the blood vessels. The segmentation was based on a HU threshold between -600 and 600 and was performed on the TLC scan. The blood vessel density can be considered a surrogate for perfusion. If a contrast agent was used, the HU threshold changed to capture voxels between 200 and 1873. The use of a contrast agent was not strictly required but recommended for patients with significant fibrosis or opaque (high attenuation) regions.
Results represent the actual values per time point, at baseline and week 24.
Lung level: TLC
Lung region: Distal lung region
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [37] - Per protocol population was used for all analyses groups [38] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
39
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [39] | ||||||||||||
P-value |
= 0.82 [40] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
-0.53
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-5.2 | ||||||||||||
upper limit |
4.38 | ||||||||||||
Notes [39] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [40] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
8_Ventilation/Perfusion Matching | ||||||||||||
End point description |
Ventilation/Perfusion matching.
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
By relating the regional ventilation to the regional perfusion, an assessment of the ventilation perfusion mismatch and potential reduction in the mismatch could be made.
Results represent the actual values per time point, at baseline and week 24.
Lung level: Not applicable
Lung region: Total lung region
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, week 24.
|
||||||||||||
|
|||||||||||||
Notes [41] - Per protocol population was used for all analyses groups [42] - Geometric coefficient of variation is the coefficient of variation for all analyses |
|||||||||||||
Statistical analysis title |
1_Percent change from baseline at week 24 | ||||||||||||
Statistical analysis description |
Percent change from baseline at week 24; within group comparison.
The value N=37 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
37
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [43] | ||||||||||||
P-value |
= 0.627 [44] | ||||||||||||
Method |
Mixed model for repeated measures | ||||||||||||
Parameter type |
Adjusted % change geometric mean | ||||||||||||
Point estimate |
-2.99
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-14.82 | ||||||||||||
upper limit |
10.49 | ||||||||||||
Notes [43] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [44] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
||||||||||||||||||||||
End point title |
9_Aerosol Deposition; BDP FF, GB | |||||||||||||||||||||
End point description |
Aerosol deposition for BDP, FF, and GB.
Percent change from baseline to week 24 of treatment.
Percent change from baseline is presented using descriptive statistics (geometric mean and coefficient of variation).
Regional aerosol deposition was determined by simulating the flow in the patient-specific geometries using patient-specific boundary conditions by means of CFD. While solving the flow equations, simultaneously particles were released in the flow and the force mass balance of the individual particles was determined through additional discrete phase computations. When a calculated particle trajectory intersected with the airway wall, the particle was trapped in that location. This allowed determining the regional concentration of inhaled aerosols and consequently the effective lung dose of inhaled medication.
Results represent the actual values per time point, at baseline and week 24.
Lung level: TLC
Lung region: Peripheral lung region
|
|||||||||||||||||||||
End point type |
Secondary
|
|||||||||||||||||||||
End point timeframe |
Baseline, week 24.
|
|||||||||||||||||||||
|
||||||||||||||||||||||
Notes [45] - Per protocol population was used for all analyses groups [46] - Geometric coefficient of variation is the coefficient of variation for all analyses |
||||||||||||||||||||||
Statistical analysis title |
1_Aerosol deposition -- BDP | |||||||||||||||||||||
Statistical analysis description |
Aerosol deposition, BDP
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
|||||||||||||||||||||
Comparison groups |
Week 24 v Baseline
|
|||||||||||||||||||||
Number of subjects included in analysis |
39
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [47] | |||||||||||||||||||||
P-value |
= 0.953 [48] | |||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | |||||||||||||||||||||
Point estimate |
0.29
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-9.49 | |||||||||||||||||||||
upper limit |
11.13 | |||||||||||||||||||||
Notes [47] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [48] - Further clarification is provided in the 'P-value comment' for end point 1. |
||||||||||||||||||||||
Statistical analysis title |
2_Aerosol deposition -- FF | |||||||||||||||||||||
Statistical analysis description |
Aerosol deposition, FF
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
|
|||||||||||||||||||||
Comparison groups |
Week 24 v Baseline
|
|||||||||||||||||||||
Number of subjects included in analysis |
39
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [49] | |||||||||||||||||||||
P-value |
= 0.952 [50] | |||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | |||||||||||||||||||||
Point estimate |
0.29
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-9.43 | |||||||||||||||||||||
upper limit |
11.07 | |||||||||||||||||||||
Notes [49] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [50] - Further clarification is provided in the 'P-value comment' for end point 1. |
||||||||||||||||||||||
Statistical analysis title |
3_Aerosol deposition -- GB | |||||||||||||||||||||
Statistical analysis description |
Aerosol deposition, GB
Percent change from baseline at week 24; within group comparison.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
|
|||||||||||||||||||||
Comparison groups |
Week 24 v Baseline
|
|||||||||||||||||||||
Number of subjects included in analysis |
39
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [51] | |||||||||||||||||||||
P-value |
= 0.951 [52] | |||||||||||||||||||||
Method |
Mixed model for repeated measures | |||||||||||||||||||||
Parameter type |
Adjusted % change geometric mean | |||||||||||||||||||||
Point estimate |
0.3
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-9.33 | |||||||||||||||||||||
upper limit |
10.96 | |||||||||||||||||||||
Notes [51] - The analysis type is a post treatment comparison versus baseline; see also the 'Analysis type comment' for end point 1. [52] - Further clarification is provided in the 'P-value comment' for end point 1. |
|
|||||||||||||
End point title |
10a_Dynamic lung volumes -- Spirometry: FEV1 | ||||||||||||
End point description |
Dynamic lung volumes calculated by spirometry: Forced Expiratory Volume in one second (FEV1)
FEV1 is one of the lung function tests, obtained by spirometry. The volume of air that can be forced out in one second after taking a deep breath is an important measure of pulmonary function.For FEV1, the highest value (L) from three technically satisfactory attempts (1 minute apart) were recorded.
Descriptive statistics were used to calculate the results shown below, which represent the actual values per time point, at baseline and at pre-dose week 24.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, pre dose at week 24.
|
||||||||||||
|
|||||||||||||
Notes [53] - Per protocol population was used for all analyses groups |
|||||||||||||
Statistical analysis title |
1_Change from baseline at week 24, FEV1 | ||||||||||||
Statistical analysis description |
Change from baseline at week 24, FEV1.
Within group comparison.
Change from baseline is presented using descriptive statistics.
The value N=40 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
40
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [54] | ||||||||||||
P-value |
= 0.296 | ||||||||||||
Method |
paired t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.056
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.052 | ||||||||||||
upper limit |
0.163 | ||||||||||||
Notes [54] - The analysis type is a comparison versus baseline. |
|
|||||||||||||
End point title |
10b_Dynamic lung volumes -- Spirometry PEF | ||||||||||||
End point description |
Dynamic lung volumes, spirometry: Peak Expiratory Flow (PEF)
PEF is one of the lung function tests, obtained by spirometry. PEF is a person's maximum speed of expiration, as measured with a peak flow meter
Descriptive statistics were used to calculate the results shown below, which represent the actual values per time point, at baseline and at pre-dose week 24.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Baseline, pre dose at week 24.
|
||||||||||||
|
|||||||||||||
Notes [55] - Per protocol population was used for all analyses groups |
|||||||||||||
Statistical analysis title |
1_Change from baseline at week 24, PEF | ||||||||||||
Statistical analysis description |
Change from baseline at week 24, PEF.
Within group comparison.
Change from baseline is presented using descriptive statistics.
The value N=40 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
||||||||||||
Comparison groups |
Week 24 v Baseline
|
||||||||||||
Number of subjects included in analysis |
40
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
other [56] | ||||||||||||
P-value |
= 0.777 | ||||||||||||
Method |
paired t-test | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Point estimate |
0.033
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.208 | ||||||||||||
upper limit |
0.274 | ||||||||||||
Notes [56] - The analysis type is a comparison versus baseline. |
|
||||||||||||||||||||||
End point title |
11_Static lung volumes -- Plethysmography: IC, TLC, RV | |||||||||||||||||||||
End point description |
Static lung volumes calculated by body plethysmography: Inspiratory capacity (IC), Total lung capacity (TLC), Residual volume (RV)
Body plethysmography is a well-established technique of lung function determination, providing measures of the lung that reflect a multitude of functional and structural aspects. It is an alternative method of measuring lung volume that takes advantage of the principle of Boyle’s law i.e. the volume of gas at a constant temperature varies inversely with the pressure applied to it. The primary advantage of body plethysmography is that it can measure the total volume of air in the chest, including gas trapped in bullae. Another advantage is that this test can be performed quickly while patient is breathing at tidal volume.
Descriptive statistics were used to calculate the results shown below, which represent the actual values per time point.
The number of patients contributing to the end points is also shown.
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End point type |
Secondary
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End point timeframe |
Baseline, pre dose at week 24.
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Notes [57] - Per protocol population was used for all analyses groups Number of subjects N=20 N=20 N=20 [58] - Number of subjects N=19 N=20 N=20 |
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Statistical analysis title |
1_Change from baseline at pre dose at week 24, IC | |||||||||||||||||||||
Statistical analysis description |
Change from baseline at pre dose on week 24, IC.
Within group comparison.
Change from baseline is presented using descriptive statistics.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
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Comparison groups |
Week 24 v Baseline
|
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Number of subjects included in analysis |
39
|
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Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [59] | |||||||||||||||||||||
P-value |
= 0.068 | |||||||||||||||||||||
Method |
paired t-test | |||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.173
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.014 | |||||||||||||||||||||
upper limit |
0.36 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.388
|
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Notes [59] - The analysis type is a comparison versus baseline. |
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Statistical analysis title |
2_Change from baseline at pre dose at week 24, TLC | |||||||||||||||||||||
Statistical analysis description |
Change from baseline at pre dose at week 24, TLC
Within group comparison.
Change from baseline is presented using descriptive statistics.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
|
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Comparison groups |
Week 24 v Baseline
|
|||||||||||||||||||||
Number of subjects included in analysis |
39
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [60] | |||||||||||||||||||||
P-value |
= 0.486 | |||||||||||||||||||||
Method |
paired t-test | |||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.118
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.228 | |||||||||||||||||||||
upper limit |
0.463 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.739
|
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Notes [60] - The analysis type is a comparison versus baseline. |
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Statistical analysis title |
3_Change from baseline at pre dose at week 24, RV | |||||||||||||||||||||
Statistical analysis description |
Change from baseline at pre dose at week 24, RV
Within group comparison.
Change from baseline is presented using descriptive statistics.
The value N=39 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=20.
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Comparison groups |
Week 24 v Baseline
|
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Number of subjects included in analysis |
39
|
|||||||||||||||||||||
Analysis specification |
Pre-specified
|
|||||||||||||||||||||
Analysis type |
other [61] | |||||||||||||||||||||
P-value |
= 0.841 | |||||||||||||||||||||
Method |
paired t-test | |||||||||||||||||||||
Parameter type |
Mean difference (final values) | |||||||||||||||||||||
Point estimate |
0.034
|
|||||||||||||||||||||
Confidence interval |
||||||||||||||||||||||
level |
95% | |||||||||||||||||||||
sides |
2-sided
|
|||||||||||||||||||||
lower limit |
-0.316 | |||||||||||||||||||||
upper limit |
0.384 | |||||||||||||||||||||
Variability estimate |
Standard deviation
|
|||||||||||||||||||||
Dispersion value |
0.747
|
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Notes [61] - The analysis type is a comparison versus baseline. |
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End point title |
12_Saint George Respiratory Questionnaire (SGRQ) | ||||||||||||||||||||||||
End point description |
Saint George Respiratory Questionnaire (SGRQ)
The SGRQ is an index designed to measure and quantify health-related health status in patients with chronic airflow limitation. Results obtained as a score from SGRQ have been shown to correlate well with established measures of symptom level, disease activity, and disability.
Three component are used to calculate the SGRQ score: Symptom level, Impacts, and Activity. A Total score is also calculated and this summarises the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and 0 indicates best possible health status.
Results show the SGRQ score at baseline and at week 24 of treatment. The number of subjects (N) contributing to the data is also indicated.
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End point type |
Secondary
|
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End point timeframe |
Baseline, week 24.
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Notes [62] - Per protocol population was used for all analyses groups Number of subjects N=19 N=19 N=19 N=20 [63] - Number of subjects N=19 N=19 N=20 N=19 |
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Statistical analysis title |
1_Change from baseline at week 24 - Total Score | ||||||||||||||||||||||||
Statistical analysis description |
Change from baseline at week 24; SGRQ Total score.
Within group comparison, using descriptive statistics.
The value N=38 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
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Comparison groups |
Baseline v Week 24
|
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Number of subjects included in analysis |
38
|
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Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [64] | ||||||||||||||||||||||||
P-value |
= 0.291 | ||||||||||||||||||||||||
Method |
paired t-test | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-2.81
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-8.22 | ||||||||||||||||||||||||
upper limit |
2.61 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||||||||
Dispersion value |
11.23
|
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Notes [64] - The analysis type is a comparison versus baseline. |
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Statistical analysis title |
2_Change from baseline at week 24; SGRQ Symptoms | ||||||||||||||||||||||||
Statistical analysis description |
Change from baseline at week 24; SGRQ Symptoms score.
Within group comparison, using descriptive statistics.
The value N=38 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
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Comparison groups |
Week 24 v Baseline
|
||||||||||||||||||||||||
Number of subjects included in analysis |
38
|
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Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [65] | ||||||||||||||||||||||||
P-value |
= 0.403 | ||||||||||||||||||||||||
Method |
paired t-test | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-3.59
|
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Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-12.39 | ||||||||||||||||||||||||
upper limit |
5.22 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||||||||
Dispersion value |
18.27
|
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Notes [65] - The analysis type is a comparison versus baseline. |
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Statistical analysis title |
3_Change from baseline at week 24; SGRQ Impacts | ||||||||||||||||||||||||
Statistical analysis description |
Change from baseline at week 24; SGRQ Impacts.
Within group comparison, using descriptive statistics.
The value N=38 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
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Comparison groups |
Week 24 v Baseline
|
||||||||||||||||||||||||
Number of subjects included in analysis |
38
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [66] | ||||||||||||||||||||||||
P-value |
= 0.74 | ||||||||||||||||||||||||
Method |
paired t-test | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
0.98
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-5.14 | ||||||||||||||||||||||||
upper limit |
7.11 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||||||||
Dispersion value |
12.71
|
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Notes [66] - The analysis type is a comparison versus baseline. |
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Statistical analysis title |
4_Change from baseline at week 24; SGRQ Activity | ||||||||||||||||||||||||
Statistical analysis description |
Change from baseline at week 24; SGRQ Activity.
Within group comparison, using descriptive statistics.
The value N=38 (Subjects in this analysis) shown below, is generated automatically and is due to an innate error of the EudraCT database system. The correct value for subjects in the analysis is N=19.
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Comparison groups |
Week 24 v Baseline
|
||||||||||||||||||||||||
Number of subjects included in analysis |
38
|
||||||||||||||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||||||||||||||
Analysis type |
other [67] | ||||||||||||||||||||||||
P-value |
= 0.131 | ||||||||||||||||||||||||
Method |
paired t-test | ||||||||||||||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||||||||||||||
Point estimate |
-8.31
|
||||||||||||||||||||||||
Confidence interval |
|||||||||||||||||||||||||
level |
95% | ||||||||||||||||||||||||
sides |
2-sided
|
||||||||||||||||||||||||
lower limit |
-19.35 | ||||||||||||||||||||||||
upper limit |
2.74 | ||||||||||||||||||||||||
Variability estimate |
Standard deviation
|
||||||||||||||||||||||||
Dispersion value |
22.91
|
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Notes [67] - The analysis type is a comparison versus baseline. |
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Adverse events information
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Timeframe for reporting adverse events |
Treatment period: from first treatment inhalation of IMP until study completion (24 weeks) or study discontinuation.
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Adverse event reporting additional description |
Analyses of adverse events were based on the safety population, defined as all randomised subjects who received at least one dose of IMP.
Adverse events were analysed according to the treatment-emergent principle.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20.0
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Reporting groups
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Reporting group title |
Subjects with COPD
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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 reported |